Sickle Cell Disease — RepurpOS

Disease overview

Alterations

168

Molecular (A)

Clinical (B–E)

Direct drugs

162

Via biomarker

348

Natural agents

Natural products

Merged ranked

508

With trial/literature evidence

Sources: Open Targets, HPO, ClinicalTrials.gov, DGIdb, ChEMBL, PubMed Literature, Examine.com, PubMed NP Literature · Pipeline phase 7 · Updated 2026-07-06

Remission & chronicity

Spontaneous remission

No spontaneous remission; progressive organ damage; median survival historically 40-60 years but improving; vaso-occlusive crises (VOC) in 1-4 per year average

Best-intervention remission

Haematopoietic stem cell transplant (HSCT): curative in 90-95% if matched sibling donor available; hydroxyurea reduces VOC frequency 50%, ACS risk 50%; gene therapy (exagamglogene autotemcel [exa-cel]/Casgevy): 30/31 patients free from severe VOC through 24 months; betibeglogene (Zynteglo): 90% reduction in severe VOC

Drug-free remission

—

Relapse after remission

—

Chronicity

—

Gap size

Very large — HSCT is curative but only 20% have matched donors; gene therapy is curative but costs $2-3M; hydroxyurea is dramatically underprescribed

Primary barrier

access

Barrier detail: Hydroxyurea is inexpensive, highly effective, and generic but prescribed to only 25-35% of eligible SCD patients (racial and healthcare access disparities prominent); gene therapies (Casgevy, Zynteglo) approved December 2023 represent first curative options without matched donor — but $2-3M price tag makes access essentially impossible without negotiation

Last SoC change: December 2023 — FDA approved exagamglogene autotemcel (Casgevy, CRISPR-based) and betibeglogene (Zynteglo) — first CRISPR-based gene therapy approvals anywhere in medicine; voxelotor (2019); crizanlizumab (2019); hydroxyurea standard since 1998

Remission data layers: disease_db_100 · source-locked manual data · confidence: high

Identifiers: MONDO: MONDO:0011382 · ORPHA: ORPHA:251380

Right to Try Relevance Critical

Eligibility: This disease meets the federal and state right-to-try legal standard (21 U.S.C. § 360bbb-0a and Montana SB 535): it lacks disease-modifying therapy with indication-specific FDA approval. Patients with Sickle Cell Disease may be eligible to access investigational therapies outside of clinical trials under right-to-try frameworks.

Investigational Agents

Phase 3: 27, Phase 2: 13

Most Advanced Phase

Phase 3

Highest dev. stage

Gene Targets

168

Actionable

Pipeline Compounds (Top 6)

Acetylcysteine, Alemtuzumab, Arginine, Arginine Hydrochloride, Bosentan, Deferasirox

Legal Standard: Right-to-try requires the disease lacks "adequate approved therapy for that specific disease" (not symptom-management drugs). This distinction means a disease with antidepressants available still qualifies if no FDA approval exists for THAT disease indication.

View Right-to-Try Compendium

Alterations

Showing 80 of 168 · Types A (molecular) through E (functional)

Name	Type	Subtype	Direction	Frequency	Evidence	Sources	Links
Abdominal pain	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Abnormality of the nervous system	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Abnormality of the spleen	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Abnormality of the vasculature	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Avascular necrosis	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Cardiomegaly	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Chest pain	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Cholelithiasis	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Chronic hemolytic anemia	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Chronic kidney disease	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Elevated circulating creatinine concentration	Lab / Clinical	Lab value	—	—	Moderate	HPO, Monarch	HPO LOINC
Finger dactylitis	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Hematuria	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Hemolytic anemia	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Hepatomegaly	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Hypertension	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Hyphema	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Hypochromic anemia	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Hypoxemia	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Increased circulating lactate dehydrogenase concentration	Lab / Clinical	Lab value	—	—	Moderate	HPO, Monarch	HPO
Increased mean corpuscular volume	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Increased red cell sickling tendency	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Increased total leukocyte count	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Intrahepatic cholestasis	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Iron deficiency anemia	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Ischemic stroke	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Jaundice	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Microcytic anemia	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Osteomyelitis	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Osteoporosis	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Pain	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Persistence of hemoglobin F	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Pigment gallstones	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Priapism	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Pulmonary arterial hypertension	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Recurrent bacterial infections	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Recurrent infections	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Renal insufficiency	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Reticulocytosis	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Retinal arterial occlusion	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Retinopathy	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Skin ulcer	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Splenic infarction	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Splenomegaly	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Stroke	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Target cells	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Thrombocytosis	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
Unconjugated hyperbilirubinemia	Pathology	Pathological finding	—	—	Moderate	HPO, Monarch	HPO
ADA adenosine deaminase	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ADORA2A adenosine A2a receptor	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ADRB1 adrenoceptor beta 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ADRB2 adrenoceptor beta 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
AGTR1 angiotensin II receptor type 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
ANK1 ankyrin 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of melphalan for HCT in pediatric patients.	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of thiotepa for HCT in pediatric patients.	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
Assessment of school absenteeism	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
BCL11A BCL11 transcription factor A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
BTK Bruton tyrosine kinase	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CACNA2D2 calcium voltage-gated channel auxiliary subunit alpha2delta 2	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CD52 CD52 molecule	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CD80 CD80 molecule	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CD86 CD86 molecule	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CHRM3 cholinergic receptor muscarinic 3	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CSF3R colony stimulating factor 3 receptor	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CXCR4 C-X-C motif chemokine receptor 4	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
CYSLTR1 cysteinyl leukotriene receptor 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Change in body composition	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
DNMT1 DNA methyltransferase 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
DNMT3A DNA methyltransferase 3 alpha	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
EDNRA endothelin receptor type A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
EDNRB endothelin receptor type B	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
EPOR erythropoietin receptor	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
Efficacy of ambrisentan in improving macro-circulation	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
Efficacy of ambrisentan in improving nociception/pain	Scales & PROs	Clinical scale	—	—	Emerging	ClinicalTrials.gov	—
Evaluate the event free survival according to the AUC of melphalan	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
Event free survival according to the AUC of thiotepa	Lab / Clinical	Lab value	—	—	Emerging	ClinicalTrials.gov	—
F10 coagulation factor X	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
FKBP1A FKBP prolyl isomerase 1A	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets
GRIN1 glutamate ionotropic receptor NMDA type subunit 1	Molecular	Gene	—	—	Emerging	Open Targets	UniProt Ensembl Open Targets

FDA-Approved Therapies

Phase 4 agents with regulatory approval for this indication

Drug Name	Mechanism	Type
ABATACEPT	inhibitor	Gene-targeted
ACALABRUTINIB	inhibitor; inhibitor	Gene-targeted
ACALABRUTINIB MALEATE	inhibitor	Gene-targeted
ACEBUTOLOL	inhibitor	Gene-targeted
ACEBUTOLOL HYDROCHLORIDE	inhibitor	Gene-targeted
ACECLIDINE	agonist	Gene-targeted
ACETAZOLAMIDE	None	Gene-targeted
ACETYLCHOLINE	agonist	Gene-targeted
ACETYLCHOLINE CHLORIDE	agonist	Gene-targeted
ACLIDINIUM	inhibitor	Gene-targeted
ACLIDINIUM BROMIDE	inhibitor	Gene-targeted
ADENOSINE	agonist; agonist	Gene-targeted
ALBUTEROL SULFATE	agonist	Gene-targeted
ALEMTUZUMAB	antibody; antibody; inhibitor	Gene-targeted
AMINOPHYLLINE	inhibitor	Gene-targeted
AMIODARONE HYDROCHLORIDE		Gene-targeted
AMITRIPTYLINE HYDROCHLORIDE	inhibitor	Gene-targeted
AMPHETAMINE	None	Gene-targeted
ANGIOTENSIN II	agonist	Gene-targeted
ANGIOTENSIN II ACETATE	agonist	Gene-targeted
ANTI-THYMOCYTE GLOBULIN		Gene-targeted
ARBUTAMINE		Gene-targeted
ARFORMOTEROL		Gene-targeted
ARFORMOTEROL TARTRATE	agonist	Gene-targeted
ASCORBIC ACID		Gene-targeted
ATENOLOL	inhibitor	Gene-targeted
ATORVASTATIN		Gene-targeted
ATORVASTATIN CALCIUM TRIHYDRATE		Gene-targeted
ATROPINE	inhibitor; inhibitor	Gene-targeted
ATROPINE SULFATE	inhibitor	Gene-targeted
AZILSARTAN KAMEDOXOMIL	inhibitor	Gene-targeted
AZILSARTAN MEDOXOMIL	inhibitor; inhibitor	Gene-targeted
BELATACEPT	inhibitor	Gene-targeted
BENAZEPRIL		Gene-targeted
BENZQUINAMIDE		Gene-targeted
BEPRIDIL HYDROCHLORIDE	blocker	Gene-targeted
BETAXOLOL	inhibitor	Gene-targeted
BETAXOLOL HYDROCHLORIDE	inhibitor	Gene-targeted
BETHANECHOL	agonist	Gene-targeted
BETHANECHOL CHLORIDE	agonist	Gene-targeted

Therapeutics

Direct disease associations, biomarker-linked drugs, OSMF narrative-review natural agents, and merged ranking. Only agents with registry trials or published clinical literature are shown by default.

Show agents without direct trial evidence

Drug	Type	Phase	Evidence	Score	Trials & literature	Sources	Links
SIROLIMUS	Small molecule	Approved	Strong	100	8 trials View evidence Registry trials NCT03263559 — Haploidentical Bone Marrow Transplantation in Sickle Cell Patients (BMTCTN1507) (COMPLETED) PHASE2 NCT02061800 — CD34+ (Malignant) Stem Cell Selection for Patients Receiving Allogenic Stem Cell Transplant (ACTIVE_NOT_RECRUITING) PHASE1, PHASE2 NCT01850108 — Non-Myeloablative Conditioning and Bone Marrow Transplantation (UNKNOWN) NA NCT02105766 — Nonmyeloablative Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Sickle Cell Disease and Beta-thalassemia in People With Higher Risk of Transplant Failure (ACTIVE_NOT_RECRUITING) PHASE2 NCT06078696 — Siplizumab for Sickle Cell Disease Transplant (TERMINATED) PHASE1, PHASE2 NCT04362293 — Reduced Intensity Transplantation for Severe Sickle Cell Disease (SUSPENDED) PHASE2 NCT03587272 — Minimizing Toxicity in HLA-identical Sibling Donor Transplantation for Children With Sickle Cell Disease (RECRUITING) PHASE2 NCT01499888 — Ph I/II Study of Allogeneic SCT for Clinically Aggressive Sickle Cell Disease (SCD) (ACTIVE_NOT_RECRUITING) PHASE1, PHASE2 CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
TACROLIMUS ANHYDROUS	Small molecule	Approved	Strong	100	8 trials View evidence Registry trials NCT03128996 — Reduced Intensity Conditioning and Familial HLA-Mismatched BMT for Non-Malignant Disorders (RECRUITING) PHASE1, PHASE2 NCT02061800 — CD34+ (Malignant) Stem Cell Selection for Patients Receiving Allogenic Stem Cell Transplant (ACTIVE_NOT_RECRUITING) PHASE1, PHASE2 NCT01565616 — Bone Marrow Transplantation in Young Adults With Severe Sickle Cell Disease (COMPLETED) PHASE2 NCT00034528 — Stem Cell Transplantation After Reduced-Dose Chemotherapy for Patients With Sickle Cell Disease or Thalassemia (TERMINATED) PHASE2 NCT04776850 — Pre-transplant Immunosuppression and Donor Stem Cell Transplant for the Treatment of Severe Hemoglobinopathies (WITHDRAWN) EARLY_PHASE1 NCT01279616 — A Reduced Toxicity Allogeneic Unrelated Donor Stem Cell Transplantation (SCT) for Severe Sickle Cell Disease (TERMINATED) PHASE2 NCT02435901 — HSCT For Patients With High Risk Hemoglobinopathies Using Reduced Intensity (COMPLETED) PHASE1, PHASE2 NCT05736419 — A Study of Immune Suppression Treatment for People With Sickle Cell Disease or β-Thalassemia Who Are Going to Receive an Allogeneic Hematopoietic Cell Transplantation (HCT) (RECRUITING) PHASE2 CT.gov search · Cochrane · PubMed	Open Targets, ChEMBL	ChEMBL Open Targets
ABATACEPT Repurposing	Small molecule	Approved	Strong	95	7 trials 1 Trial pubs View evidence Registry trials NCT03128996 — Reduced Intensity Conditioning and Familial HLA-Mismatched BMT for Non-Malignant Disorders (RECRUITING) PHASE1, PHASE2 NCT07599176 — Partial Stem Cell Transplant for Sickle Cell Disease From Matched Donors (RECRUITING) PHASE1, PHASE2 NCT07616154 — Haploidentical Donor Hematopoietic Cell Transplant for Sickle Cell Disease (NOT_YET_RECRUITING) PHASE2 NCT03924401 — Acute GVHD Suppression Using Costimulation Blockade to Expand Non-malignant Transplant (ACTIVE_NOT_RECRUITING) PHASE2 NCT06145282 — Non-myeloablative Haploidentical HCT Study for Patients With Sickle Cell Disease, Including Compromised Organ Function (ACTIVE_NOT_RECRUITING) PHASE1, PHASE2 NCT02867800 — Abatacept for GVHD Prophylaxis After Hematopoietic Stem Cell Transplantation for Pediatric Sickle Cell Disease (COMPLETED) PHASE1 NCT01917708 — Bone Marrow Transplant With Abatacept for Non-Malignant Diseases (COMPLETED) PHASE1 Published literature Clinical trial publication Abatacept is effective as GVHD prophylaxis in unrelated donor stem cell transplantation for children with severe sickle cell disease (Blood advances, 2020) CT.gov search · Cochrane · PubMed	DGIdb	—
ACALABRUTINIB Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ACALABRUTINIB MALEATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ACEBUTOLOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ACEBUTOLOL HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ACECLIDINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ACETAZOLAMIDE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
ACETYLCHOLINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ACETYLCHOLINE CHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ACLIDINIUM Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ACLIDINIUM BROMIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ADENOSINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ALBUTEROL SULFATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ALEMTUZUMAB Repurposing	Small molecule	Approved	Strong	95	8 trials 14 Trial pubs View evidence Registry trials NCT03128996 — Reduced Intensity Conditioning and Familial HLA-Mismatched BMT for Non-Malignant Disorders (RECRUITING) PHASE1, PHASE2 NCT02061800 — CD34+ (Malignant) Stem Cell Selection for Patients Receiving Allogenic Stem Cell Transplant (ACTIVE_NOT_RECRUITING) PHASE1, PHASE2 NCT00176852 — Stem Cell Transplant for Hemoglobinopathy (COMPLETED) PHASE2, PHASE3 NCT01962415 — Reduced Intensity Conditioning for Non-Malignant Disorders Undergoing UCBT, BMT or PBSCT (RECRUITING) PHASE2 NCT00408447 — Stem Cell Transplant in Sickle Cell Disease and Thalassemia (UNKNOWN) PHASE2 NCT02105766 — Nonmyeloablative Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Sickle Cell Disease and Beta-thalassemia in People With Higher Risk of Transplant Failure (ACTIVE_NOT_RECRUITING) PHASE2 NCT05249452 — Adding Azathioprine/Hydroxyurea Preconditioning to Alemtuzumab/TBI to Reduce Risk of Graft Failure in MSD HSCT in Adult SCD Patients (COMPLETED) NCT03653338 — T-Cell Depleted Alternative Donor Bone Marrow Transplant for Sickle Cell Disease (SCD) and Other Anemias (RECRUITING) PHASE1, PHASE2 Published literature Clinical trial publication Nonmyeloablative HLA-identical sibling transplant for sickle cell disease in children: a multicenter prospective study (Blood advances, 2026) Clinical trial publication Alemtuzumab clearance, lymphocyte count, and T-cell chimerism after hematopoietic stem cell transplant in sickle cell disease (Pharmacotherapy, 2022) Clinical trial publication Non-myeloablative human leukocyte antigen-matched related donor transplantation in sickle cell disease: outcomes from three independent centres (British journal of haematology, 2021) Clinical trial publication Timing of Alemtuzumab With Respect to Day of Bone Marrow Infusion and its Effects Upon Engraftment and Graft-Versus-Host Disease in Patients With Sickle Cell Disease: A Single-Institutional Study (Journal of pediatric hematology/oncology, 2020) Clinical trial publication Abatacept is effective as GVHD prophylaxis in unrelated donor stem cell transplantation for children with severe sickle cell disease (Blood advances, 2020) CT.gov search · Cochrane · PubMed	DGIdb	—
AMINOPHYLLINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
AMIODARONE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
AMITRIPTYLINE HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
AMPHETAMINE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
ANGIOTENSIN II Repurposing	Small molecule	Approved	Strong	95	2 trials View evidence Registry trials NCT03944447 — Outcomes Mandate National Integration With Cannabis as Medicine (UNKNOWN) PHASE2 NCT04053764 — Study Exploring the Effect of Crizanlizumab on Kidney Function in Patients With Chronic Kidney Disease Caused by Sickle Cell Disease (COMPLETED) PHASE2 CT.gov search · Cochrane · PubMed	DGIdb	—
ANGIOTENSIN II ACETATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ANTI-THYMOCYTE GLOBULIN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ARBUTAMINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ARFORMOTEROL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ARFORMOTEROL TARTRATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ASCORBIC ACID Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ATENOLOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ATORVASTATIN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ATORVASTATIN CALCIUM TRIHYDRATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ATROPINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
ATROPINE SULFATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
AZILSARTAN KAMEDOXOMIL Repurposing	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	ChEMBL Open Targets
AZILSARTAN MEDOXOMIL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
BELATACEPT Repurposing	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	—
BENAZEPRIL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
BENZQUINAMIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
BEPRIDIL HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
BETAXOLOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
BETAXOLOL HYDROCHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
BETHANECHOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
BETHANECHOL CHLORIDE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
BETHANIDINE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
BEVACIZUMAB Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
BICALUTAMIDE Repurposing	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
BIPERIDEN Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
BISOPROLOL Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—
BISOPROLOL FUMARATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
BITOLTEROL MESYLATE Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
BRETYLIUM Repurposing	Small molecule	Approved	Strong	95	—	DGIdb	—

Drug	Type	Phase	Evidence	Score	Sources	Links
ACETYLCYSTEINE	Small molecule	Phase III	Moderate	80	Open Targets	ChEMBL Open Targets
ALEMTUZUMAB	Biologic	Phase III	Moderate	80	Open Targets	ChEMBL Open Targets
ARGININE	Small molecule	Phase III	Moderate	80	Open Targets	ChEMBL Open Targets
ARGININE HYDROCHLORIDE	Small molecule	Phase III	Moderate	80	Open Targets	ChEMBL Open Targets
BOSENTAN	Small molecule	Phase III	Moderate	80	Open Targets	ChEMBL Open Targets
DEFERASIROX	Small molecule	Phase III	Moderate	80	Open Targets	ChEMBL Open Targets
DEXAMETHASONE	Small molecule	Phase III	Moderate	80	Open Targets	ChEMBL Open Targets
ETAVOPIVAT	Small molecule	Phase III	Moderate	80	Open Targets	ChEMBL Open Targets
FILGRASTIM	Biologic	Phase III	Moderate	80	Open Targets	ChEMBL Open Targets
FLUDARABINE	Small molecule	Phase III	Moderate	80	Open Targets	ChEMBL Open Targets
INCLACUMAB	Biologic	Phase III	Moderate	80	Open Targets	ChEMBL Open Targets
KETAMINE	Small molecule	Phase III	Moderate	80	Open Targets	ChEMBL Open Targets
KETAMINE HYDROCHLORIDE	Small molecule	Phase III	Moderate	80	Open Targets	ChEMBL Open Targets
L-CITRULLINE	Small molecule	Phase III	Moderate	80	Open Targets	ChEMBL Open Targets
LENOGRASTIM	Biologic	Phase III	Moderate	80	Open Targets	ChEMBL Open Targets
MAGNESIUM SULFATE	Small molecule	Phase III	Moderate	80	Open Targets	ChEMBL Open Targets
MELPHALAN	Small molecule	Phase III	Moderate	80	Open Targets	ChEMBL Open Targets
METHYLPHENIDATE	Small molecule	Phase III	Moderate	80	Open Targets	ChEMBL Open Targets
MORPHINE	Small molecule	Phase III	Moderate	80	Open Targets	ChEMBL Open Targets
PARECOXIB	Small molecule	Phase III	Moderate	80	Open Targets	ChEMBL Open Targets
PEGFILGRASTIM	Biologic	Phase III	Moderate	80	Open Targets	ChEMBL Open Targets
PRASUGREL	Small molecule	Phase III	Moderate	80	Open Targets	ChEMBL Open Targets
RILZABRUTINIB	Small molecule	Phase III	Moderate	80	Open Targets	ChEMBL Open Targets
ROVATIRELIN	Small molecule	Phase III	Moderate	80	Open Targets	ChEMBL Open Targets
SENICAPOC	Small molecule	Phase III	Moderate	80	Open Targets	ChEMBL Open Targets
SUFENTANIL	Small molecule	Phase III	Moderate	80	Open Targets	ChEMBL Open Targets
VEPOLOXAMER	Small molecule	Phase III	Moderate	80	Open Targets	ChEMBL Open Targets
ABCIXIMAB	Biologic	Phase II	Emerging	60	Open Targets	ChEMBL Open Targets
ACETYLCARNITINE	Small molecule	Phase II	Emerging	60	Open Targets	ChEMBL Open Targets
ACETYLCHOLINE	Small molecule	Phase II	Emerging	60	Open Targets	ChEMBL Open Targets
ANTILYMPHOCYTE IMMUNOGLOBULIN (HORSE)	Small molecule	Phase II	Emerging	60	Open Targets	ChEMBL Open Targets
ANUMIGILIMAB	Biologic	Phase II	Emerging	60	Open Targets	ChEMBL Open Targets
ATORVASTATIN	Small molecule	Phase II	Emerging	60	Open Targets	ChEMBL Open Targets
AZATHIOPRINE	Small molecule	Phase II	Emerging	60	Open Targets	ChEMBL Open Targets
BORTEZOMIB	Small molecule	Phase II	Emerging	60	Open Targets	ChEMBL Open Targets
BUPRENORPHINE	Small molecule	Phase II	Emerging	60	Open Targets	ChEMBL Open Targets
BUSULFAN	Small molecule	Phase II	Emerging	60	Open Targets	ChEMBL Open Targets
CANAKINUMAB	Biologic	Phase II	Emerging	60	Open Targets	ChEMBL Open Targets
CHLOROQUINE	Small molecule	Phase II	Emerging	60	Open Targets	ChEMBL Open Targets
CYCLOPHOSPHAMIDE	Small molecule	Phase II	Emerging	60	Open Targets	ChEMBL Open Targets

Drug	Type	Phase	Evidence	Score	Trials & literature	Sources	Links
ABATACEPT Repurposing via CD80	Small molecule	Approved	Strong	95	7 trials 1 Trial pubs View evidence Registry trials NCT03128996 — Reduced Intensity Conditioning and Familial HLA-Mismatched BMT for Non-Malignant Disorders (RECRUITING) PHASE1, PHASE2 NCT07599176 — Partial Stem Cell Transplant for Sickle Cell Disease From Matched Donors (RECRUITING) PHASE1, PHASE2 NCT07616154 — Haploidentical Donor Hematopoietic Cell Transplant for Sickle Cell Disease (NOT_YET_RECRUITING) PHASE2 NCT03924401 — Acute GVHD Suppression Using Costimulation Blockade to Expand Non-malignant Transplant (ACTIVE_NOT_RECRUITING) PHASE2 NCT06145282 — Non-myeloablative Haploidentical HCT Study for Patients With Sickle Cell Disease, Including Compromised Organ Function (ACTIVE_NOT_RECRUITING) PHASE1, PHASE2 NCT02867800 — Abatacept for GVHD Prophylaxis After Hematopoietic Stem Cell Transplantation for Pediatric Sickle Cell Disease (COMPLETED) PHASE1 NCT01917708 — Bone Marrow Transplant With Abatacept for Non-Malignant Diseases (COMPLETED) PHASE1 Published literature Clinical trial publication Abatacept is effective as GVHD prophylaxis in unrelated donor stem cell transplantation for children with severe sickle cell disease (Blood advances, 2020) CT.gov search · Cochrane · PubMed	DGIdb	—
ACALABRUTINIB Repurposing via BTK	Small molecule	Approved	Strong	95	—	DGIdb	—
ACALABRUTINIB MALEATE Repurposing via BTK	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ACEBUTOLOL Repurposing via ADRB1	Small molecule	Approved	Strong	95	—	DGIdb	—
ACEBUTOLOL HYDROCHLORIDE Repurposing via ADRB1	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ACECLIDINE Repurposing via CHRM3	Small molecule	Approved	Strong	95	—	DGIdb	—
ACETAZOLAMIDE Repurposing via ADA	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
ACETYLCHOLINE Repurposing via CHRM3	Small molecule	Approved	Strong	95	—	DGIdb	—
ACETYLCHOLINE CHLORIDE Repurposing via CHRM3	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ACLIDINIUM Repurposing via CHRM3	Small molecule	Approved	Strong	95	—	DGIdb	—
ACLIDINIUM BROMIDE Repurposing via CHRM3	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ADENOSINE Repurposing via ADORA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
ALBUTEROL SULFATE Repurposing via ADRB2	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ALEMTUZUMAB Repurposing via CD52	Small molecule	Approved	Strong	95	8 trials 14 Trial pubs View evidence Registry trials NCT03128996 — Reduced Intensity Conditioning and Familial HLA-Mismatched BMT for Non-Malignant Disorders (RECRUITING) PHASE1, PHASE2 NCT02061800 — CD34+ (Malignant) Stem Cell Selection for Patients Receiving Allogenic Stem Cell Transplant (ACTIVE_NOT_RECRUITING) PHASE1, PHASE2 NCT00176852 — Stem Cell Transplant for Hemoglobinopathy (COMPLETED) PHASE2, PHASE3 NCT01962415 — Reduced Intensity Conditioning for Non-Malignant Disorders Undergoing UCBT, BMT or PBSCT (RECRUITING) PHASE2 NCT00408447 — Stem Cell Transplant in Sickle Cell Disease and Thalassemia (UNKNOWN) PHASE2 NCT02105766 — Nonmyeloablative Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Sickle Cell Disease and Beta-thalassemia in People With Higher Risk of Transplant Failure (ACTIVE_NOT_RECRUITING) PHASE2 NCT05249452 — Adding Azathioprine/Hydroxyurea Preconditioning to Alemtuzumab/TBI to Reduce Risk of Graft Failure in MSD HSCT in Adult SCD Patients (COMPLETED) NCT03653338 — T-Cell Depleted Alternative Donor Bone Marrow Transplant for Sickle Cell Disease (SCD) and Other Anemias (RECRUITING) PHASE1, PHASE2 Published literature Clinical trial publication Nonmyeloablative HLA-identical sibling transplant for sickle cell disease in children: a multicenter prospective study (Blood advances, 2026) Clinical trial publication Alemtuzumab clearance, lymphocyte count, and T-cell chimerism after hematopoietic stem cell transplant in sickle cell disease (Pharmacotherapy, 2022) Clinical trial publication Non-myeloablative human leukocyte antigen-matched related donor transplantation in sickle cell disease: outcomes from three independent centres (British journal of haematology, 2021) Clinical trial publication Timing of Alemtuzumab With Respect to Day of Bone Marrow Infusion and its Effects Upon Engraftment and Graft-Versus-Host Disease in Patients With Sickle Cell Disease: A Single-Institutional Study (Journal of pediatric hematology/oncology, 2020) Clinical trial publication Abatacept is effective as GVHD prophylaxis in unrelated donor stem cell transplantation for children with severe sickle cell disease (Blood advances, 2020) CT.gov search · Cochrane · PubMed	DGIdb	—
AMINOPHYLLINE Repurposing via ADORA2A	Small molecule	Approved	Strong	95	—	DGIdb	—
AMIODARONE HYDROCHLORIDE Repurposing via ADRB1	Small molecule	Approved	Strong	95	—	DGIdb	—
AMITRIPTYLINE HYDROCHLORIDE Repurposing via CHRM3	Small molecule	Approved	Strong	95	—	DGIdb	—
AMPHETAMINE Repurposing via ADA	Small molecule	Approved	Strong	95	—	ChEMBL	ChEMBL Open Targets
ANGIOTENSIN II Repurposing via AGTR1	Small molecule	Approved	Strong	95	2 trials View evidence Registry trials NCT03944447 — Outcomes Mandate National Integration With Cannabis as Medicine (UNKNOWN) PHASE2 NCT04053764 — Study Exploring the Effect of Crizanlizumab on Kidney Function in Patients With Chronic Kidney Disease Caused by Sickle Cell Disease (COMPLETED) PHASE2 CT.gov search · Cochrane · PubMed	DGIdb	—
ANGIOTENSIN II ACETATE Repurposing via AGTR1	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ANTI-THYMOCYTE GLOBULIN Repurposing via CD86	Small molecule	Approved	Strong	95	—	DGIdb	—
ARBUTAMINE Repurposing via ADRB1	Small molecule	Approved	Strong	95	—	DGIdb	—
ARFORMOTEROL Repurposing via ADRB2	Small molecule	Approved	Strong	95	—	DGIdb	—
ARFORMOTEROL TARTRATE Repurposing via ADRB2	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
ASCORBIC ACID Repurposing via AGTR1	Small molecule	Approved	Strong	95	—	DGIdb	—
ATENOLOL Repurposing via ADRB2	Small molecule	Approved	Strong	95	—	DGIdb	—
ATORVASTATIN Repurposing via AGTR1	Small molecule	Approved	Strong	95	—	DGIdb	—
ATORVASTATIN CALCIUM TRIHYDRATE Repurposing via AGTR1	Small molecule	Approved	Strong	95	—	DGIdb	—
ATROPINE Repurposing via CHRM3	Small molecule	Approved	Strong	95	—	DGIdb	—
ATROPINE SULFATE Repurposing via CHRM3	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
AZILSARTAN KAMEDOXOMIL Repurposing via AGTR1	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	ChEMBL Open Targets
AZILSARTAN MEDOXOMIL Repurposing via AGTR1	Small molecule	Approved	Strong	95	—	DGIdb	—
BELATACEPT Repurposing via CD80	Small molecule	Approved	Strong	95	No indexed hits View evidence CT.gov search · Cochrane · PubMed	DGIdb	—
BENAZEPRIL Repurposing via AGTR1	Small molecule	Approved	Strong	95	—	DGIdb	—
BENZQUINAMIDE Repurposing via CHRM3	Small molecule	Approved	Strong	95	—	DGIdb	—
BEPRIDIL HYDROCHLORIDE Repurposing via CACNA2D2	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
BETAXOLOL Repurposing via ADRB2	Small molecule	Approved	Strong	95	—	DGIdb	—
BETAXOLOL HYDROCHLORIDE Repurposing via ADRB1	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets
BETHANECHOL Repurposing via CHRM3	Small molecule	Approved	Strong	95	—	DGIdb	—
BETHANECHOL CHLORIDE Repurposing via CHRM3	Small molecule	Approved	Strong	95	—	DGIdb	ChEMBL Open Targets

Natural Products

30 natural products with the same evidence schema as repurposed drugs — registry trials, PubMed literature, and reference links (pipeline-ranked). Only agents with direct clinical evidence are shown by default.

Reference lookups: Examine.com

Show agents without direct trial evidence

Drug	Type	Phase	Evidence	Score	Trials & literature	Sources	Links
L-Arginine Natural product	Amino acid	Approved	Moderate	17	8 trials 2 Cochrane 10 Trial pubs View evidence Registry trials NCT01718054 — Vascular Function Intervention Trial in Sickle Cell Disease (UNKNOWN) PHASE2, PHASE3 NCT00056433 — Evaluation of Hydroxyurea Plus L-arginine or Sildenafil to Treat Sickle Cell Anemia (COMPLETED) PHASE1 NCT02636387 — Desmopressin as a Therapy for Bedwetting in Children With Sickle Cell Disease (TERMINATED) NCT00029731 — Arginine Treatment of Acute Chest Syndrome (Pneumonia) in Sickle Cell Disease Patients (COMPLETED) PHASE2 NCT05470998 — L-Arginine in Children Having Sickle Cell Disease With Increased Tricuspid Regurgitant Jet Velocity (COMPLETED) PHASE3 NCT00009581 — Nitric Oxide to Improve Blood Flow in Sickle Cell Disease (COMPLETED) PHASE2 NCT02536170 — Arginine Therapy for Sickle Cell Disease Pain (COMPLETED) PHASE2 NCT04420585 — Desmopressin for Bedwetting in Children With SCD (TERMINATED) PHASE4 CT.gov search · Cochrane · PubMed	Examine.com	PubChem Examine.com
L-Arginine Natural product Arginine therapy in sickle cell disease: A systematic review and meta-a… The efficacy of oral L-arginine therapy for the treatment of vaso-occlu… Clinical Study to Evaluate the Possible Efficacy and Safety of L-Argini…	Amino acid	Approved	Emerging	16	8 trials 2 Cochrane 10 Trial pubs View evidence Registry trials NCT01718054 — Vascular Function Intervention Trial in Sickle Cell Disease (UNKNOWN) PHASE2, PHASE3 NCT00056433 — Evaluation of Hydroxyurea Plus L-arginine or Sildenafil to Treat Sickle Cell Anemia (COMPLETED) PHASE1 NCT02636387 — Desmopressin as a Therapy for Bedwetting in Children With Sickle Cell Disease (TERMINATED) NCT00029731 — Arginine Treatment of Acute Chest Syndrome (Pneumonia) in Sickle Cell Disease Patients (COMPLETED) PHASE2 NCT05470998 — L-Arginine in Children Having Sickle Cell Disease With Increased Tricuspid Regurgitant Jet Velocity (COMPLETED) PHASE3 NCT00009581 — Nitric Oxide to Improve Blood Flow in Sickle Cell Disease (COMPLETED) PHASE2 NCT02536170 — Arginine Therapy for Sickle Cell Disease Pain (COMPLETED) PHASE2 NCT04420585 — Desmopressin for Bedwetting in Children With SCD (TERMINATED) PHASE4 CT.gov search · Cochrane · PubMed	Examine.com	PubChem Examine.com
Vitamin C Natural product Human Study Antioxidant vitamin levels are depleted in sickle cell disorders, indic… Human Study Chronic, oral, low-dose vitamin C supplementation equilibrates autonomi… Human Study Vitamin C and/or warmth have a positive effect on forearm blood flow an…	Nutraceutical	Phase II	Emerging	10	2 trials 3 Cochrane 1 Meta-analysis View evidence Registry trials NCT02567682 — Drug Interaction Study of GBT440 With Caffeine, S-warfarin, Omeprazole, and Midazolam in Healthy Subjects (COMPLETED) PHASE1 NCT04514510 — Fixed Dose Flavonoid Isoquercetin on Thrombo-Inflammatory Biomarkers in Subjects With Stable Sickle Cell Disease (COMPLETED) PHASE2 CT.gov search · Cochrane · PubMed		PubChem
Vitamin E Natural product Cochrane review Antioxidant supplementation for sickle cell disease Randomized controlled trial Docosahexaenoic and eicosapentaenoic acid supplementation does not exac… Human Study Antioxidant vitamin levels are depleted in sickle cell disorders, indic…	Nutraceutical	Approved	Emerging	10	2 trials 1 Cochrane 1 Meta-analysis 1 RCT View evidence Registry trials NCT03903133 — Endothelial Monocyte-activating Polypeptide-II in Egyptian Sickle Patients (COMPLETED) PHASE4 NCT02525107 — Prevention of Vaso-occlusive Painful Crisis by Using Omega-3 Fatty Acid Supplements (UNKNOWN) PHASE3 Published literature Cochrane review Antioxidant supplementation for sickle cell disease (The Cochrane database of systematic reviews, 2024) Randomized controlled trial Docosahexaenoic and eicosapentaenoic acid supplementation does not exacerbate oxidative stress or intravascular haemolysis in homozygous sickle cell patients (Prostaglandins, leukotrienes, and essential fatty acids, 2013) CT.gov search · Cochrane · PubMed		PubChem
Vitamin D3 Natural product Cochrane review Vitamin D supplementation for sickle cell disease Cochrane review Vitamin D supplementation for sickle cell disease Meta-analysis The effects of nutritional supplementation for children and adolescents…	Nutraceutical	Approved	Emerging	10	8 trials 2 Cochrane 2 Meta-analysis 2 Trial pubs 1 RCT View evidence Registry trials NCT03417947 — Vitamin D Supplementation in Children With Sickle Cell Disease (COMPLETED) PHASE3 NCT01276587 — Study of Vitamin D in Children With Sickle Cell Disease (COMPLETED) PHASE1, PHASE2 NCT03012555 — Vitamin D3 in Patients With Sickle Cell Disease (COMPLETED) NCT01443728 — Vitamin D for Sickle-cell Respiratory Complications (COMPLETED) PHASE2 NCT04662476 — Vitamin D Supplementation in Children With Sickle Cell Disease (UNKNOWN) NA NCT03176849 — A Randomized Phase IV Control Trial of Single High Dose Oral Vitamin D3 in Pediatric Patients Undergoing HSCT (COMPLETED) PHASE4 NCT01331148 — High Dose Vitamin D for Sickle Cell Disease (COMPLETED) PHASE2 NCT04170348 — Daily Vitamin D for Sickle-cell Respiratory Complications (COMPLETED) PHASE2 Published literature Cochrane review Vitamin D supplementation for sickle cell disease (The Cochrane database of systematic reviews, 2020) Cochrane review Vitamin D supplementation for sickle cell disease (The Cochrane database of systematic reviews, 2017) Meta-analysis The effects of nutritional supplementation for children and adolescents with sickle cell disease: A systematic review and meta-analyses (Clinical nutrition (Edinburgh, Scotland), 2025) Clinical trial publication Safety and efficacy of monthly high-dose vitamin D(3) supplementation in children and adolescents with sickle cell disease (European journal of pediatrics, 2024) Clinical trial publication Safety and Efficacy of High-dose Daily Vitamin D3 Supplementation in Children and Young Adults With Sickle Cell Disease (Journal of pediatric hematology/oncology, 2015) CT.gov search · Cochrane · PubMed		PubChem
Zinc Natural product Clinical trial publication Zinc level and its impact on the phenotype of sickle cell disease Clinical trial publication Zinc finger nuclease-mediated gene editing in hematopoietic stem cells… Clinical trial publication No improvement in suboptimal vitamin A status with a randomized, double…	Nutraceutical	Phase III	Emerging	10	7 trials 11 Cochrane 8 Meta-analysis 10 Trial pubs View evidence Registry trials NCT03528434 — Zinc for Infection Prevention in Sickle Cell Anemia (ZIPS) (COMPLETED) NA NCT03653247 — A Study to Assess the Safety, Tolerability, and Efficacy of BIVV003 for Autologous Hematopoietic Stem Cell Transplantation in Patients With Severe Sickle Cell Disease (COMPLETED) PHASE1, PHASE2 NCT04479618 — Test of the Safety, Effectiveness, & Acceptability of An Improvised Dressing for Sickle Cell Leg Ulcers in the Tropics (COMPLETED) NA NCT03293641 — Zinc Supplementation in Children With Sickle Cell Disease in Western Kenya (COMPLETED) NA NCT06561061 — Zinc for Infection Prevention in Sickle Cell Anemia-2 (ZIPS-2) (COMPLETED) PHASE2, PHASE3 NCT06260891 — Zinc Supplementation in Sickle Cell Disease: A Precursor to the Think Zinc for Bones Trial (RECRUITING) PHASE2 NCT04301336 — Different Treatment Modalities in the Management of the Painful Crisis in Pediatric Sickle- Cell Anemia (COMPLETED) PHASE2, PHASE3 Published literature Clinical trial publication Zinc level and its impact on the phenotype of sickle cell disease (Annals of hematology, 2025) Clinical trial publication Zinc finger nuclease-mediated gene editing in hematopoietic stem cells results in reactivation of fetal hemoglobin in sickle cell disease (Scientific reports, 2024) Clinical trial publication No improvement in suboptimal vitamin A status with a randomized, double-blind, placebo-controlled trial of vitamin A supplementation in children with sickle cell disease (The American journal of clinical nutrition, 2012) Clinical trial publication Zinc supplementation decreases oxidative stress, incidence of infection, and generation of inflammatory cytokines in sickle cell disease patients (Translational research : the journal of laboratory and clinical medicine, 2008) Clinical trial publication Iron deficiency anaemia in sickle cell disorders in India (The Indian journal of medical research, 2008) CT.gov search · Cochrane · PubMed		PubChem
Omega-3 Fatty Acids Natural product Cochrane review DHA and EPA in Sickle Cell Disease Favor Clinical Improvement and Contr… Cochrane review Antioxidant nutrients and hemolysis in sickle cell disease Cochrane review Pharmacotherapeutical strategies in the prevention of acute, vaso-occlu…	Nutraceutical	Phase III	Emerging	10	8 trials 3 Cochrane 5 Trial pubs 3 RCT View evidence Registry trials NCT02947100 — Omega-3 Fatty Acids in Sickle Cell Disease (TERMINATED) PHASE1, PHASE2 NCT01202812 — A Randomized Trial of LOVAZA in Pediatric Sickle Cell Disease (SCD) (UNKNOWN) PHASE2 NCT02973360 — Dose-Finding Study of SC411 in Children With Sickle Cell Disease (UNKNOWN) PHASE2 NCT02604368 — A Sickle CEll Disease ComplicatioN Trial (UNKNOWN) PHASE3 NCT05758766 — Study on Use of Omega-3 Fatty Acids to Improve Outcomes in Individuals With Sickle Cell Disease (ACTIVE_NOT_RECRUITING) NA NCT02525107 — Prevention of Vaso-occlusive Painful Crisis by Using Omega-3 Fatty Acid Supplements (UNKNOWN) PHASE3 NCT04301336 — Different Treatment Modalities in the Management of the Painful Crisis in Pediatric Sickle- Cell Anemia (COMPLETED) PHASE2, PHASE3 NCT07530965 — OMEGA-3-FATTY ACIDS IN CHILDREN WITH SICKLE CELL DISEASE (NOT_YET_RECRUITING) NA Published literature Cochrane review DHA and EPA in Sickle Cell Disease Favor Clinical Improvement and Contribute to Better Quality of Life: A Qualitative Systematic Review (Current drug research reviews, 2025) Cochrane review Antioxidant nutrients and hemolysis in sickle cell disease (Clinica chimica acta; international journal of clinical chemistry, 2020) Cochrane review Pharmacotherapeutical strategies in the prevention of acute, vaso-occlusive pain in sickle cell disease: a systematic review (Blood advances, 2017) Clinical trial publication An open-label, multicenter, phase 2 study of a food enriched with docosahexaenoic acid in adults with sickle cell disease (Prostaglandins, leukotrienes, and essential fatty acids, 2023) Clinical trial publication Omega 3 (n-3) fatty acids down-regulate nuclear factor-kappa B (NF-κB) gene and blood cell adhesion molecule expression in patients with homozygous sickle cell disease (Blood cells, molecules & diseases, 2015) Clinical trial publication Docosahexaenoic and eicosapentaenoic acid supplementation does not exacerbate oxidative stress or intravascular haemolysis in homozygous sickle cell patients (Prostaglandins, leukotrienes, and essential fatty acids, 2013) Clinical trial publication Effect of omega-3 (n-3) fatty acid supplementation in patients with sickle cell anemia: randomized, double-blind, placebo-controlled trial (The American journal of clinical nutrition, 2013) Clinical trial publication Pilot study of omega-3 fatty acid supplements in sickle cell disease (APMIS : acta pathologica, microbiologica, et immunologica Scandinavica, 2011) CT.gov search · Cochrane · PubMed		PubChem
Magnesium Natural product Cochrane review The Role of Non-genetic Therapies to Reduce the Incidence of Sickle Cel… Cochrane review Magnesium for treating sickle cell disease Cochrane review Magnesium for treating sickle cell disease	Nutraceutical	Phase III	Emerging	10	6 trials 3 Cochrane 3 Meta-analysis 3 Trial pubs 2 RCT View evidence Registry trials NCT00143572 — Use of Hydroxyurea and Magnesium Pidolate for Treatment of Sickle Cell Disease (COMPLETED) PHASE1 NCT00313963 — MAST - Magnesium for Sickle Cell Acute Crisis in Children (COMPLETED) PHASE3 NCT00276146 — Dipyridamole/Magnesium To Improve Sickle Cell Hydration (WITHDRAWN) PHASE2 NCT00040456 — Oral Magnesium Pidolate, Hemoglobin SC Disease, MG Pidolate (TERMINATED) PHASE2 NCT01197417 — Intravenous Magnesium for Sickle Cell Vasoocclusive Crisis (COMPLETED) PHASE2, PHASE3 NCT00532883 — Hydroxyurea and Magnesium Pidolate to Treat People With Hemoglobin Sickle Cell Disease (TERMINATED) PHASE2 Published literature Cochrane review The Role of Non-genetic Therapies to Reduce the Incidence of Sickle Cell Crisis: A Systematic Review (Cureus, 2023) Cochrane review Magnesium for treating sickle cell disease (The Cochrane database of systematic reviews, 2019) Cochrane review Magnesium for treating sickle cell disease (The Cochrane database of systematic reviews, 2017) Meta-analysis The effects of nutritional supplementation for children and adolescents with sickle cell disease: A systematic review and meta-analyses (Clinical nutrition (Edinburgh, Scotland), 2025) Meta-analysis Adjuvant interventions with opioids for vaso-occlusive crisis in sickle cell disease: A mixed treatment network meta-analysis of randomized controlled clinical trials (Journal of opioid management, 2020) Meta-analysis Analgesic management of uncomplicated acute sickle-cell pain crisis in pediatrics: a systematic review and meta-analysis (Jornal de pediatria, 2020) Clinical trial publication Impact of emergency department care on outcomes of acute pain events in children with sickle cell disease (American journal of hematology, 2016) Clinical trial publication Intravenous magnesium sulfate for vaso-occlusive episodes in sickle cell disease (Pediatrics, 2013) Clinical trial publication Oral magnesium supplements reduce erythrocyte dehydration in patients with sickle cell disease (The Journal of clinical investigation, 1997) CT.gov search · Cochrane · PubMed		PubChem
Glutamine Natural product Cochrane review Newer Modalities and Updates in the Management of Sickle Cell Disease:… Cochrane review Emerging Therapies for the Management of Pain and Vaso-Occlusive Crises… Cochrane review Contemporary Management and Prevention of Vaso-Occlusive Crises (VOCs)…	Amino acid	Approved	Emerging	10	7 trials 5 Cochrane 1 Meta-analysis 5 Trial pubs 2 RCT View evidence Registry trials NCT00586209 — L-Glutamine Therapy for Sickle Cell Anemia (TERMINATED) PHASE2 NCT00131508 — Trial of Oral Glutamine in Patients With Sickle Cell Anemia (TERMINATED) PHASE2 NCT00125788 — L-Glutamine Therapy for Sickle Cell Anemia and Sickle ß0 Thalassemia (COMPLETED) PHASE2 NCT01179217 — A Phase III Safety and Efficacy Study of L-Glutamine to Treat Sickle Cell Disease or Sickle βo-thalassemia (COMPLETED) PHASE3 NCT04684381 — Pharmacokinetics and Safety of Endari (L-glutamine) in Sickle Cell Disease Patients (COMPLETED) PHASE4 NCT05371184 — Glutamine Role in Preventing Vaso-occlusive Crisis Among SCD Patients (COMPLETED) PHASE4 NCT01048905 — Glutamine Therapy for Hemolysis-Associated Pulmonary Hypertension (COMPLETED) PHASE2 Published literature Cochrane review Newer Modalities and Updates in the Management of Sickle Cell Disease: A Systematic Review (Journal of blood medicine, 2024) Cochrane review Emerging Therapies for the Management of Pain and Vaso-Occlusive Crises in Patients With Sickle Cell Disease: A Systematic Review of Randomized Controlled Trials (Cureus, 2023) Cochrane review Contemporary Management and Prevention of Vaso-Occlusive Crises (VOCs) in Adults With Sickle Cell Disease (Journal of pharmacy practice, 2023) Cochrane review Systematic Review of l-glutamine for Prevention of Vaso-occlusive Pain Crisis in Patients with Sickle Cell Disease (Pharmacotherapy, 2019) Cochrane review Pharmacotherapeutical strategies in the prevention of acute, vaso-occlusive pain in sickle cell disease: a systematic review (Blood advances, 2017) Meta-analysis Crizanlizumab and comparators for adults with sickle cell disease: a systematic review and network meta-analysis (BMJ open, 2020) Systematic review Evidence and gaps in clinical outcomes of novel pharmacologic therapies for sickle cell disease: A systematic literature review highlighting insights from clinical trials and real-world studies (Blood reviews, 2025) Systematic review Health-Related Quality of Life and Adherence to Hydroxyurea and Other Disease-Modifying Therapies among Individuals with Sickle Cell Disease: A Systematic Review (BioMed research international, 2022) Systematic review Systematic Review of Crizanlizumab: A New Parenteral Option to Reduce Vaso-occlusive Pain Crises in Patients with Sickle Cell Disease (Pharmacotherapy, 2020) Clinical trial publication Safety and efficacy of L-Glutamine in reducing the frequency of acute complications among patients with sickle cell disease: A randomized controlled study (Annals of hematology, 2024) Clinical trial publication A Population Pharmacokinetic Analysis of L-Glutamine Exposure in Patients with Sickle Cell Disease: Evaluation of Dose and Food Effects (Clinical pharmacokinetics, 2024) Clinical trial publication The effects of glutamine supplementation on markers of apoptosis and autophagy in sickle cell disease peripheral blood mononuclear cells (Complementary therapies in medicine, 2022) CT.gov search · Cochrane · PubMed		PubChem
N-Acetylcysteine Natural product Cochrane review Antioxidant supplementation for sickle cell disease Meta-analysis Efficacy and Safety of N-Acetylcysteine for the Management of Chronic P… Clinical trial publication Effect of N-acetylcysteine on pain in daily life in patients with sickl…	Amino acid	Phase III	Emerging	10	2 trials 1 Cochrane 2 Meta-analysis 3 Trial pubs 3 RCT View evidence Registry trials NCT01800526 — A Pilot Study of N-acetylcysteine in Patients With Sickle Cell Disease (COMPLETED) PHASE1, PHASE2 NCT01849016 — N-Acetylcysteine in Patients With Sickle Cell Disease (COMPLETED) PHASE3 Published literature Cochrane review Antioxidant supplementation for sickle cell disease (The Cochrane database of systematic reviews, 2024) Meta-analysis Efficacy and Safety of N-Acetylcysteine for the Management of Chronic Pain in Adults: A Systematic Review and Meta-Analysis (Pain medicine (Malden, Mass.), 2021) Clinical trial publication Effect of N-acetylcysteine on pain in daily life in patients with sickle cell disease: a randomised clinical trial (British journal of haematology, 2018) Clinical trial publication N-acetylcysteine reduces oxidative stress in sickle cell patients (Annals of hematology, 2012) Clinical trial publication Effects of N-acetylcysteine on dense cell formation in sickle cell disease (American journal of hematology, 2003) CT.gov search · Cochrane · PubMed		PubChem
Garlic Natural product In Vitro Study Aged garlic extract and other antioxidant nutritional supplements exhib…	Food compound	Preclinical	Emerging	10	2 pubs View evidence CT.gov search · Cochrane · PubMed		PubChem
Sulforaphane Natural product Clinical trial publication Phase 1 Study of a Sulforaphane-Containing Broccoli Sprout Homogenate f… Animal Study Dietary supplementation with sulforaphane attenuates liver damage and h…	Food compound	Preclinical	Emerging	7	1 trials 1 Trial pubs View evidence Registry trials NCT01715480 — Effect of Broccoli Sprouts Homogenate on SS RBC (COMPLETED) NA Published literature Clinical trial publication Phase 1 Study of a Sulforaphane-Containing Broccoli Sprout Homogenate for Sickle Cell Disease (PloS one, 2016) CT.gov search · Cochrane · PubMed		PubChem
Curcumin Natural product Transgenic Animal Study Curcumin and CoQ10 independently as well as in combination ameliorate c… Animal Study Curcumin may represent a new horizon in managing iron overload-induced…	Food compound	Preclinical	Emerging	7	6 pubs View evidence CT.gov search · Cochrane · PubMed		PubChem
L-Citrulline Natural product Human Study Citrulline and spirulina may have a therapeutic role in the management…	Amino acid	Phase III	Emerging	7	8 trials View evidence Registry trials NCT01718054 — Vascular Function Intervention Trial in Sickle Cell Disease (UNKNOWN) PHASE2, PHASE3 NCT06989567 — A Study of Intravenous L-Citrulline in Patients Aged 6-21 Years Old With Sickle Cell Disease Presenting to Emergency Departments in Acute Vaso-Occlusive Crisis (NOT_YET_RECRUITING) PHASE3 NCT02659644 — A Study of Oral L-citrulline in Sickle Cell Disease (WITHDRAWN) PHASE1 NCT02697240 — A Phase 1 Study of Continuous Intravenous L-citrulline During Sickle Cell Pain Crisis or Acute Chest Syndrome (COMPLETED) PHASE1 NCT04852172 — L-citrulline Injection in Patients Aged 6-21 Years Old with Sickle Cell Disease Presenting with Vaso-Occlusive Crisis (VOC) (TERMINATED) PHASE1, PHASE2 NCT02314689 — A Dose Escalation Study of Intravenous L-citrulline in Steady-state Sickle Cell Disease (COMPLETED) PHASE1 NCT00343954 — PK and PD Responses to Oral L-Citrulline in Patients With Sickle Cell Disease (UNKNOWN) PHASE1 NCT06635902 — Intravenous L-Citrulline for Vaso-occlusive Pain Episode in Sickle Cell Disease (RECRUITING) PHASE2 CT.gov search · Cochrane · PubMed		PubChem
Spirulina Natural product Human Study Citrulline and spirulina may have a therapeutic role in the management…	Nutraceutical	Preclinical	Emerging	7	1 pubs View evidence CT.gov search · Cochrane · PubMed		—
Andrographis Natural product Animal Study, In Vitro Study Investigating the potential use of andrographolide as a coadjuvant in s…	Botanical	Preclinical	Emerging	7	No indexed hits View evidence CT.gov search · Cochrane · PubMed		PubChem
Coenzyme Q10 Natural product Transgenic Animal Study Curcumin and CoQ10 independently as well as in combination ameliorate c…	Nutraceutical	Preclinical	Emerging	7	No indexed hits View evidence CT.gov search · Cochrane · PubMed		PubChem
Alpha-Lipoic Acid Natural product Clinical trial publication Alpha-lipoic acid modifies oxidative stress parameters in sickle cell t… Review "Sickle cell anemia: a potential nutritional approach for a molecu…	Nutraceutical	Phase II	Emerging	7	1 trials 1 Trial pubs 1 RCT View evidence Registry trials NCT01054768 — Antioxidant Therapy to Reduce Inflammation in Sickle Cell Disease (COMPLETED) PHASE2 Published literature Clinical trial publication Alpha-lipoic acid modifies oxidative stress parameters in sickle cell trait subjects and sickle cell patients (Clinical nutrition (Edinburgh, Scotland), 2009) CT.gov search · Cochrane · PubMed		PubChem
Egcg Natural product Review "Sickle cell anemia: a potential nutritional approach for a molecu…	Food compound	Preclinical	Emerging	7	No indexed hits View evidence CT.gov search · Cochrane · PubMed		PubChem
Antioxidant Formulas Natural product Human Study Zinc and antioxidant vitamin deficiency in patients with severe sickle… In Vitro Study Aged garlic extract and other antioxidant nutritional supplements exhib… Human Study Antioxidant vitamin levels are depleted in sickle cell disorders, indic…	Nutraceutical	Preclinical	Emerging	0	No indexed hits View evidence CT.gov search · Cochrane · PubMed		—
Broccoli Sprouts Natural product Human Study Broccoli sprout homogenate is safe in stable SCD patients and may induc…	Nutraceutical	Preclinical	Emerging	0	—		—
Lime Natural product Human Study Influence of lime juice on the severity of sickle cell anemia.	Nutraceutical	Preclinical	Emerging	0	—		—
Rehmannia Natural product Human Study Rehmannia contains a compound which may be of value in treating sickle…	Nutraceutical	Preclinical	Emerging	0	—		—
Nigella Sativa (Aka Black Seed) Natural product Human Study The fixed oil extracted from Nigella sativa seeds has an in vitro antis…	Nutraceutical	Preclinical	Emerging	0	—		—
Palmitoylethanolamide Natural product Animal Study Neuroprotective, anti-inflammatory, and analgesic activity of palmitoyl…	Nutraceutical	Preclinical	Emerging	0	—		—
Beta-Carotene Natural product Review "Sickle cell anemia: a potential nutritional approach for a molecu…	Nutraceutical	Preclinical	Emerging	0	—		—
Black Tea Natural product Review "Sickle cell anemia: a potential nutritional approach for a molecu…	Nutraceutical	Preclinical	Emerging	0	—		—
Pycnogenol (Pine Bark) Natural product Review "Sickle cell anemia: a potential nutritional approach for a molecu…	Nutraceutical	Preclinical	Emerging	0	—		—
Polyphenols Natural product Review Antioxidant-rich nutraceutical as a therapeutic strategy for sickle cel…	Nutraceutical	Preclinical	Emerging	0	—		—
Suma (Pfaffia Paniculata) Natural product In Vitro Study Suma appears to have valuable application in the treatment of sickle ce…	Nutraceutical	Preclinical	Emerging	0	—		—

Alterations and therapeutics are aggregated from public databases (Open Targets, HPO, ChEMBL, DGIdb, and others). Natural agents are candidates from OSMF narrative reviews on opensourcemed.info/chronic-disease.html — not approved treatments. This page is for research orientation only — not medical advice.