Remission & chronicity

Spontaneous remission

Acute Lyme: spontaneous resolution in some untreated patients but dissemination and late manifestations develop; PTLDS (persistent symptoms after adequate antibiotics): affects 10-20% of patients; spontaneous resolution of PTLDS in 50-60% by 6 months

Best-intervention remission

Acute Lyme: 14-21 day doxycycline achieves 80-95% cure; PTLDS: no treatment shown superior to placebo in 4 large RCTs; prolonged antibiotic therapy (IDSA-condemned) not effective; symptom management only

Gap size

Large for PTLDS — the field lacks an evidence-based treatment and has been mired in controversy over mechanism and management

Primary barrier

biological (PTLDS mechanism uncertain) + framing (controversy)

PTLDS treatment is one of the most contentious areas in medicine; IDSA position (no benefit of prolonged antibiotics) vs ILADS position (chronic infection requiring extended treatment) — RCTs support IDSA; the patient experience of persistent symptoms is real but the mechanism may not be ongoing active infection; this creates a significant care gap for suffering patients

Biomarker Targets & Therapeutic Agents

Gene targets queried against DGIdb, Open Targets, ChEMBL, PubMed, and Europe PMC. Agents ranked: Clinical > Mechanistic > Correlative.

CXCL13 1 IFNG 31 IL17A 76 IL1B 216 IL6 181 NLRP3 156 PTGS2 309 TLR1 0 TLR2 190 TNF 287

CXCL13

UniProt Ensembl DGIdb Open Targets

Therapeutic Agent	Effect Direction	Evidence Tier	Potency	Source
RITUXIMAB	? unclear	Mechanistic		DGIdb

IFNG

UniProt Ensembl DGIdb Open Targets

Therapeutic Agent	Effect Direction	Evidence Tier	Potency	Source
GANCICLOVIR	? unclear	Mechanistic		DGIdb
EMAPALUMAB	↓ inhibits	Mechanistic		DGIdb
PEFLOXACIN	? unclear	Mechanistic		DGIdb
TRETINOIN	? unclear	Mechanistic		DGIdb
AMITRIPTYLINE HYDROCHLORIDE	? unclear	Mechanistic		DGIdb
MELPHALAN	? unclear	Mechanistic		DGIdb
CISPLATIN	? unclear	Mechanistic		DGIdb
EDRECOLOMAB	? unclear	Mechanistic		DGIdb
METHYLPREDNISOLONE	? unclear	Mechanistic		DGIdb
DOXIFLURIDINE	? unclear	Mechanistic		DGIdb
CYCLOPHOSPHAMIDE ANHYDROUS	? unclear	Mechanistic		DGIdb
URSODIOL	? unclear	Mechanistic		DGIdb
PREDNISONE	? unclear	Mechanistic		DGIdb
BLEOMYCIN	? unclear	Mechanistic		DGIdb
AMIKACIN	? unclear	Mechanistic		DGIdb
THERAPEUTIC GLUCOCORTICOID	? unclear	Mechanistic		DGIdb
FONTOLIZUMAB	↓ inhibits	Mechanistic		DGIdb
AMG-811	↓ inhibits	Mechanistic		DGIdb
THEOPHYLLINE	? unclear	Mechanistic		DGIdb
PENICILLIN G POTASSIUM	? unclear	Mechanistic		DGIdb
TRASTUZUMAB	? unclear	Mechanistic		DGIdb
FUMARIC ACID	? unclear	Mechanistic		DGIdb
SURAMIN	? unclear	Mechanistic		DGIdb
IBUPROFEN, SODIUM SALT	? unclear	Mechanistic		DGIdb
THERAPEUTIC MELATONIN	? unclear	Mechanistic		DGIdb
THERAPEUTIC AUTOLOGOUS LYMPHOCYTES	? unclear	Mechanistic		DGIdb
THROMBIN ALFA	? unclear	Mechanistic		DGIdb
INTERFERON ALFA-2B	? unclear	Mechanistic		DGIdb
RECOMBINANT INTERLEUKIN-1-BETA	? unclear	Mechanistic		DGIdb
CHEMBL3288259	↓ inhibits	Mechanistic	10000.0 nM (Kd)	ChEMBL
CHEMBL3288260	↓ inhibits	Mechanistic	7000.0 nM (Kd)	ChEMBL

IL17A

UniProt Ensembl DGIdb Open Targets

Therapeutic Agent	Effect Direction	Evidence Tier	Potency	Source
M-1095	↓ inhibits	Mechanistic		DGIdb
ANTI-IL17A MONOCLONAL ANTIBODY CJM112	? unclear	Mechanistic		DGIdb
VUNAKIZUMAB	↓ inhibits	Mechanistic		DGIdb
SIMVASTATIN	? unclear	Mechanistic		DGIdb
IZOKIBEP	↓ inhibits	Mechanistic		DGIdb
CJM-112	~ modulates	Mechanistic		DGIdb
IXEKIZUMAB	↓ inhibits	Mechanistic		DGIdb
COVA322	? unclear	Mechanistic		DGIdb
FLUTICASONE/SALMETEROL	? unclear	Mechanistic		DGIdb
BRODALUMAB	? unclear	Mechanistic		DGIdb
REMTOLUMAB	↓ inhibits	Mechanistic		DGIdb
ABBV-257	? unclear	Mechanistic		DGIdb
BIMEKIZUMAB	↓ inhibits	Mechanistic		DGIdb
VIDOFLUDIMUS	? unclear	Mechanistic		DGIdb
ERYTHROMYCIN	? unclear	Mechanistic		DGIdb
TIBULIZUMAB	↓ inhibits	Mechanistic		DGIdb
TETRACYCLINE	? unclear	Mechanistic		DGIdb
MANNITOL	? unclear	Mechanistic		DGIdb
GENTAMICIN	? unclear	Mechanistic		DGIdb
SECUKINUMAB	↓ inhibits	Mechanistic		DGIdb
SIROLIMUS	? unclear	Mechanistic		DGIdb
BUDESONIDE	? unclear	Mechanistic		DGIdb
OMALIZUMAB	? unclear	Mechanistic		DGIdb
EDODEKIN ALFA	? unclear	Mechanistic		DGIdb
AFASEVIKUMAB	↓ inhibits	Mechanistic		DGIdb
FORMOTEROL FUMARATE	? unclear	Mechanistic		DGIdb
AZATHIOPRINE	? unclear	Mechanistic		DGIdb
PERAKIZUMAB	↓ inhibits	Mechanistic		DGIdb
CHEMBL4872876	↓ inhibits	Mechanistic	110.0 nM (Kd)	ChEMBL
CHEMBL4858175	↓ inhibits	Mechanistic	12.3 nM (Kd)	ChEMBL
CHEMBL4854787	↓ inhibits	Mechanistic	89.0 nM (Kd)	ChEMBL
CHEMBL4878993	↓ inhibits	Mechanistic	12.9 nM (Kd)	ChEMBL
CHEMBL4869568	↓ inhibits	Mechanistic	6.2 nM (Kd)	ChEMBL
CHEMBL4876088	↓ inhibits	Mechanistic	10.1 nM (IC50)	ChEMBL
CHEMBL4860250	↓ inhibits	Mechanistic	14.3 nM (IC50)	ChEMBL
CHEMBL4866932	↓ inhibits	Mechanistic	10.1 nM (IC50)	ChEMBL
CHEMBL4874078	↓ inhibits	Mechanistic	7.0 nM (IC50)	ChEMBL
CHEMBL4845695	↓ inhibits	Mechanistic	2.8 nM (IC50)	ChEMBL
CHEMBL4855085	↓ inhibits	Mechanistic	4.6 nM (IC50)	ChEMBL
CHEMBL4860574	↓ inhibits	Mechanistic	2.0 nM (IC50)	ChEMBL

Showing top 40 of 76 agents ranked by evidence tier.

IL1B

UniProt Ensembl DGIdb Open Targets

Therapeutic Agent	Effect Direction	Evidence Tier	Source
METFORMIN	? unclear	Mechanistic	DGIdb
NICARDIPINE HYDROCHLORIDE	? unclear	Mechanistic	DGIdb
CANAKINUMAB	↓ inhibits	Mechanistic	DGIdb
TT-301	? unclear	Mechanistic	DGIdb
LITHIUM CATION	? unclear	Mechanistic	DGIdb
THYROGLOBULIN	? unclear	Mechanistic	DGIdb
LUTIKIZUMAB	? unclear	Mechanistic	DGIdb
CEFACLOR ANHYDROUS	? unclear	Mechanistic	DGIdb
CLODRONIC ACID	? unclear	Mechanistic	DGIdb
CELASTROL	? unclear	Mechanistic	DGIdb
ACITRETIN	? unclear	Mechanistic	DGIdb
RESVERATROL	? unclear	Mechanistic	DGIdb
INFLIXIMAB	? unclear	Mechanistic	DGIdb
PENTAMIDINE	? unclear	Mechanistic	DGIdb
DRUGSATFDA.NDA:008378	? unclear	Mechanistic	DGIdb
RILONACEPT	↓ inhibits	Mechanistic	DGIdb
USTEKINUMAB	? unclear	Mechanistic	DGIdb
BECLOMETHASONE DIPROPIONATE	? unclear	Mechanistic	DGIdb
DIACETYLRHEIN	? unclear	Mechanistic	DGIdb
RISEDRONIC ACID	? unclear	Mechanistic	DGIdb
HYDROCORTISONE BUTYRATE	? unclear	Mechanistic	DGIdb
ECHINACEA EXTRACT	? unclear	Mechanistic	DGIdb
CHINESE HERBS	? unclear	Mechanistic	DGIdb
ETIDRONIC ACID	? unclear	Mechanistic	DGIdb
OFLOXACIN	? unclear	Mechanistic	DGIdb
CYTARABINE	? unclear	Mechanistic	DGIdb
CDP-484	↓ inhibits	Mechanistic	DGIdb
ERYTHROMYCIN	? unclear	Mechanistic	DGIdb
THERAPEUTIC MELATONIN	? unclear	Mechanistic	DGIdb
PRAVASTATIN SODIUM	? unclear	Mechanistic	DGIdb
GALLIUM NITRATE	? unclear	Mechanistic	DGIdb
PENTOXIFYLLINE	? unclear	Mechanistic	DGIdb
ANTIDEPRESSANT AGENT	? unclear	Mechanistic	DGIdb
VERAPAMIL	? unclear	Mechanistic	DGIdb
TETRADECANOYLPHORBOL ACETATE	? unclear	Mechanistic	DGIdb
HYDROQUINONE	? unclear	Mechanistic	DGIdb
RALOXIFENE HYDROCHLORIDE	? unclear	Mechanistic	DGIdb
ANTICONVULSANT AGENT	? unclear	Mechanistic	DGIdb
NIMUSTINE	? unclear	Mechanistic	DGIdb
POLYVALENT VACCINE	? unclear	Mechanistic	DGIdb

Showing top 40 of 216 agents ranked by evidence tier.

IL6

UniProt Ensembl DGIdb Open Targets

Therapeutic Agent	Effect Direction	Evidence Tier	Source
CLAZAKIZUMAB	↓ inhibits	Mechanistic	DGIdb
MIDOSTAURIN	? unclear	Mechanistic	DGIdb
ECHINACEA EXTRACT	? unclear	Mechanistic	DGIdb
NELFINAVIR	? unclear	Mechanistic	DGIdb
SELECTIVE ESTROGEN RECEPTOR MODULATOR	? unclear	Mechanistic	DGIdb
SIGNAL TRANSDUCTION INHIBITOR	? unclear	Mechanistic	DGIdb
OLOKIZUMAB	? unclear	Mechanistic	DGIdb
IBUDILAST	? unclear	Mechanistic	DGIdb
VITAMIN A PALMITATE	? unclear	Mechanistic	DGIdb
IFOSFAMIDE	? unclear	Mechanistic	DGIdb
SITAGLIPTIN	? unclear	Mechanistic	DGIdb
METRONIDAZOLE	? unclear	Mechanistic	DGIdb
PEGINTERFERON ALFA-2A	? unclear	Mechanistic	DGIdb
PACIBEKITUG	↓ inhibits	Mechanistic	DGIdb
PEGINTERFERON ALFA-2B	? unclear	Mechanistic	DGIdb
SIRUKUMAB	↓ inhibits	Mechanistic	DGIdb
HMG-COA REDUCTASE INHIBITOR	? unclear	Mechanistic	DGIdb
SAFINGOL	? unclear	Mechanistic	DGIdb
ENZYME INHIBITOR	? unclear	Mechanistic	DGIdb
CISPLATIN	? unclear	Mechanistic	DGIdb
GALLIUM NITRATE	? unclear	Mechanistic	DGIdb
RITUXIMAB	? unclear	Mechanistic	DGIdb
INFLIXIMAB	? unclear	Mechanistic	DGIdb
C326	? unclear	Mechanistic	DGIdb
GEMFIBROZIL	? unclear	Mechanistic	DGIdb
ZILTIVEKIMAB	? unclear	Mechanistic	DGIdb
INSULIN, REGULAR, HUMAN	? unclear	Mechanistic	DGIdb
OSIMERTINIB	? unclear	Mechanistic	DGIdb
BINETRAKIN	? unclear	Mechanistic	DGIdb
ALOGLIPTIN	? unclear	Mechanistic	DGIdb
TENELIGLIPTIN	? unclear	Mechanistic	DGIdb
CHINESE HERBS	? unclear	Mechanistic	DGIdb
TOCILIZUMAB	? unclear	Mechanistic	DGIdb
LINAGLIPTIN	? unclear	Mechanistic	DGIdb
DOCETAXEL ANHYDROUS	? unclear	Mechanistic	DGIdb
VILDAGLIPTIN	? unclear	Mechanistic	DGIdb
LINEZOLID	? unclear	Mechanistic	DGIdb
SELENIUM	? unclear	Mechanistic	DGIdb
SAQUINAVIR	? unclear	Mechanistic	DGIdb
PAREGORIC	? unclear	Mechanistic	DGIdb

Showing top 40 of 181 agents ranked by evidence tier.

NLRP3

UniProt DGIdb Open Targets

Therapeutic Agent	Effect Direction	Evidence Tier	Potency	Source
MCC950	↓ inhibits	Mechanistic		DGIdb
TRICLOCARBAN	? unclear	Mechanistic	1490.0 nM (IC50)	DGIdb
CY-09	↓ inhibits	Mechanistic		DGIdb
EMLENOFLAST	↓ inhibits	Mechanistic		DGIdb
ETANERCEPT	? unclear	Mechanistic		DGIdb
CHEMBL:CHEMBL601543	? unclear	Mechanistic		DGIdb
DAPANSUTRILE	↓ inhibits	Mechanistic		DGIdb
ORIDONIN DERIVATIVE 32 [PMID: 38751194]	↓ inhibits	Mechanistic		DGIdb
NDT-19795	↓ inhibits	Mechanistic		DGIdb
NT-0796	↓ inhibits	Mechanistic		DGIdb
COMPOUND 15Z [PMID: 38029358]	↓ inhibits	Mechanistic		DGIdb
ANAKINRA	? unclear	Mechanistic		DGIdb
CHEMBL:CHEMBL602526	? unclear	Mechanistic		DGIdb
SELNOFLAST	↓ inhibits	Mechanistic		DGIdb
4'-METHOXYFLAVONE	? unclear	Mechanistic	31000.0 nM (IC50)	DGIdb
CLIOXANIDE	? unclear	Mechanistic	1610.0 nM (IC50)	DGIdb
ENCLOMIPHENE CITRATE	? unclear	Mechanistic		DGIdb
NLRP3 INHIBITOR 3 [PMID: 33255820]	↓ inhibits	Mechanistic		DGIdb
RRX-001	↓ inhibits	Mechanistic		DGIdb
COMPOUND 17 [WO2024240153]	↓ inhibits	Mechanistic		DGIdb
INFLIXIMAB	? unclear	Mechanistic		DGIdb
ORIDONIN	↓ inhibits	Mechanistic		DGIdb
NT-0249	↓ inhibits	Mechanistic		DGIdb
ALAPROCLATE HYDROCHLORIDE	? unclear	Mechanistic	8020.0 nM (IC50)	DGIdb
YCT-529	↓ inhibits	Mechanistic		DGIdb
GDC-2394	~ modulates	Mechanistic		DGIdb
CP-424,174	↓ inhibits	Mechanistic		DGIdb
CHEMBL1336269	↓ inhibits	Mechanistic	8010.0 nM (IC50)	ChEMBL
CHEMBL1596681	↓ inhibits	Mechanistic	9020.0 nM (IC50)	ChEMBL
CHEMBL1447078	↓ inhibits	Mechanistic	53900.0 nM (IC50)	ChEMBL
CHEMBL1457403	↓ inhibits	Mechanistic	4790.0 nM (IC50)	ChEMBL
CHEMBL1539913	↓ inhibits	Mechanistic	35400.0 nM (IC50)	ChEMBL
CHEMBL1366588	↓ inhibits	Mechanistic	2070.0 nM (IC50)	ChEMBL
CHEMBL1709001	↓ inhibits	Mechanistic	14900.0 nM (IC50)	ChEMBL
CHEMBL1329507	↓ inhibits	Mechanistic	11000.0 nM (IC50)	ChEMBL
CHEMBL1507547	↓ inhibits	Mechanistic	76600.0 nM (IC50)	ChEMBL
CLOMIPHENE	↓ inhibits	Mechanistic	29300.0 nM (IC50)	ChEMBL
CHEMBL1339092	↓ inhibits	Mechanistic	11700.0 nM (IC50)	ChEMBL
CHEMBL1574982	↓ inhibits	Mechanistic	3530.0 nM (IC50)	ChEMBL
CHEMBL1558285	↓ inhibits	Mechanistic	14300.0 nM (IC50)	ChEMBL

Showing top 40 of 156 agents ranked by evidence tier.

PTGS2

UniProt Ensembl DGIdb Open Targets

Therapeutic Agent	Effect Direction	Evidence Tier	Potency	Source
CURCUMIN PYRAZOLE	? unclear	Mechanistic		DGIdb
CAPECITABINE	? unclear	Mechanistic		DGIdb
DIFLUNISAL	↓ inhibits	Mechanistic		DGIdb
ROFECOXIB	↓ inhibits	Mechanistic	530.0 nM (IC50)	DGIdb
KETOROLAC TROMETHAMINE	↓ inhibits	Mechanistic		DGIdb
DEXIBUPROFEN	↓ inhibits	Mechanistic		DGIdb
BALSALAZIDE	? unclear	Mechanistic		DGIdb
ESFLURBIPROFEN	↓ inhibits	Mechanistic		DGIdb
NAPROXEN ETEMESIL	? unclear	Mechanistic		DGIdb
SUPROFEN	↓ inhibits	Mechanistic		DGIdb
PEPTIDE 30 [PMID: 27019010]	↓ inhibits	Mechanistic		DGIdb
NEPAFENAC	↓ inhibits	Mechanistic		DGIdb
APRICOXIB	↓ inhibits	Mechanistic		DGIdb
APAZONE	↓ inhibits	Mechanistic		DGIdb
SALICYLIC ACID	? unclear	Mechanistic		DGIdb
TIAPROFENIC ACID	? unclear	Mechanistic		DGIdb
KETOPROFEN	↓ inhibits	Mechanistic		DGIdb
RESERPINE	? unclear	Mechanistic		DGIdb
NS-398	↓ inhibits	Mechanistic		DGIdb
NABUMETONE	↓ inhibits	Mechanistic		DGIdb
SULINDAC	↓ inhibits	Mechanistic		DGIdb
ETODOLAC	↓ inhibits	Mechanistic		DGIdb
MEFENAMIC ACID	↓ inhibits	Mechanistic		DGIdb
DICLOFENAC SODIUM	↓ inhibits	Mechanistic		DGIdb
ETORICOXIB	↓ inhibits	Mechanistic		DGIdb
VALDECOXIB	↓ inhibits	Mechanistic		DGIdb
IBUFENAC	↓ inhibits	Mechanistic		DGIdb
DEXKETOPROFEN	↓ inhibits	Mechanistic		DGIdb
GLAFENINE	↓ inhibits	Mechanistic		DGIdb
COMPOUND 9 [KUMAR ET AL., 2019]	↓ inhibits	Mechanistic		DGIdb
RESVERATROL	↓ inhibits	Mechanistic		DGIdb
SWE101	↓ inhibits	Mechanistic		DGIdb
INDOMETHACIN	↓ inhibits	Mechanistic	5.9 nM (IC50)	DGIdb
NAPROXCINOD	↓ inhibits	Mechanistic		DGIdb
HR1405-01	↓ inhibits	Mechanistic		DGIdb
DICLOFENAC ETALHYALURONATE SODIUM	↓ inhibits	Mechanistic		DGIdb
COMPOUND 12A [PMID: 29031075]	↓ inhibits	Mechanistic		DGIdb
TOLMETIN SODIUM	↓ inhibits	Mechanistic		DGIdb
OXYPHENBUTAZONE	↓ inhibits	Mechanistic		DGIdb
DICLOFENAC POTASSIUM	↓ inhibits	Mechanistic		DGIdb

Showing top 40 of 309 agents ranked by evidence tier.

TLR1

UniProt Ensembl DGIdb Open Targets

Pipeline results not yet available for this target. Run the pipeline to populate.

TLR2

UniProt Ensembl DGIdb Open Targets

Therapeutic Agent	Effect Direction	Evidence Tier	Potency	Source
TLR AGONIST CADI-05	? unclear	Mechanistic		DGIdb
ADALIMUMAB	? unclear	Mechanistic		DGIdb
PAREGORIC	? unclear	Mechanistic		DGIdb
TOMARALIMAB	? unclear	Mechanistic		DGIdb
DIAPEP277	? unclear	Mechanistic		DGIdb
INFLIXIMAB	? unclear	Mechanistic		DGIdb
VB-201	↓ inhibits	Mechanistic		DGIdb
DIPROVOCIM-1	↑ activates	Mechanistic		DGIdb
RESVERATROL HEXANOIC ACID	? unclear	Mechanistic		DGIdb
DEFOSLIMOD	? unclear	Mechanistic		DGIdb
CHEMBL:CHEMBL1836411	? unclear	Mechanistic		DGIdb
COMPOUND 13 [PMID: 23098072]	↑ activates	Mechanistic		DGIdb
PEPTIDOGLYCAN	↑ activates	Mechanistic		DGIdb
CHEMBL382272	↓ inhibits	Mechanistic	3070.0 nM (IC50)	ChEMBL
CHEMBL383597	↓ inhibits	Mechanistic	900.0 nM (IC50)	ChEMBL
CHEMBL372577	↓ inhibits	Mechanistic	950.0 nM (IC50)	ChEMBL
CHEMBL380585	↓ inhibits	Mechanistic	5200.0 nM (IC50)	ChEMBL
CHEMBL190383	↓ inhibits	Mechanistic	1250.0 nM (IC50)	ChEMBL
CHEMBL200206	↓ inhibits	Mechanistic	2150.0 nM (IC50)	ChEMBL
CHEMBL200140	↓ inhibits	Mechanistic	22000.0 nM (IC50)	ChEMBL
CHEMBL200667	↓ inhibits	Mechanistic	6900.0 nM (IC50)	ChEMBL
CHEMBL200398	↓ inhibits	Mechanistic	6460.0 nM (IC50)	ChEMBL
MYRISTIC ACID	↓ inhibits	Mechanistic	5000.0 nM (IC50)	ChEMBL
PALMITIC ACID	↓ inhibits	Mechanistic	5000.0 nM (IC50)	ChEMBL
CHEMBL490908	↓ inhibits	Mechanistic	230.0 nM (IC50)	ChEMBL
CHEMBL446794	↓ inhibits	Mechanistic	900.0 nM (IC50)	ChEMBL
CHEMBL448621	↓ inhibits	Mechanistic	240.0 nM (IC50)	ChEMBL
CHEMBL473383	↓ inhibits	Mechanistic	460.0 nM (IC50)	ChEMBL
CHEMBL414311	↓ inhibits	Mechanistic	5000.0 nM (IC50)	ChEMBL
CHEMBL1092429	↓ inhibits	Mechanistic	48.0 nM (IC50)	ChEMBL
CHEMBL1092428	↓ inhibits	Mechanistic	1200.0 nM (IC50)	ChEMBL
CHEMBL1923536	↑ activates	Mechanistic	0.45 nM (EC50)	ChEMBL
CHEMBL1923537	↑ activates	Mechanistic	1.0 nM (EC50)	ChEMBL
CHEMBL1923538	↑ activates	Mechanistic	0.87 nM (EC50)	ChEMBL
CHEMBL1923540	↑ activates	Mechanistic	6.48 nM (EC50)	ChEMBL
CHEMBL1923541	↑ activates	Mechanistic	0.56 nM (EC50)	ChEMBL
CHEMBL1923542	↑ activates	Mechanistic	1.47 nM (EC50)	ChEMBL
CHEMBL1923544	↑ activates	Mechanistic	2.11 nM (EC50)	ChEMBL
CHEMBL1923545	↑ activates	Mechanistic	1.55 nM (EC50)	ChEMBL
CHEMBL1923546	↑ activates	Mechanistic	3.23 nM (EC50)	ChEMBL

Showing top 40 of 190 agents ranked by evidence tier.

TNF

UniProt Ensembl DGIdb Open Targets

Therapeutic Agent	Effect Direction	Evidence Tier	Source
DICLOFENAC SODIUM	? unclear	Mechanistic	DGIdb
RDP58	? unclear	Mechanistic	DGIdb
METHYLENE BLUE	? unclear	Mechanistic	DGIdb
ORTATAXEL	? unclear	Mechanistic	DGIdb
CERTOLIZUMAB PEGOL	↓ inhibits	Mechanistic	DGIdb
OZORALIZUMAB	↓ inhibits	Mechanistic	DGIdb
THALIDOMIDE	? unclear	Mechanistic	DGIdb
HUANG LIAN	? unclear	Mechanistic	DGIdb
GOLIMUMAB	↓ inhibits	Mechanistic	DGIdb
CYCLOSPORINE	? unclear	Mechanistic	DGIdb
DOCETAXEL ANHYDROUS	? unclear	Mechanistic	DGIdb
HALOFUGINONE	? unclear	Mechanistic	DGIdb
ETANERCEPT	↓ inhibits	Mechanistic	DGIdb
ISIS 104838	? unclear	Mechanistic	DGIdb
GEMCITABINE	? unclear	Mechanistic	DGIdb
INDOMETHACIN	? unclear	Mechanistic	DGIdb
INSULIN, REGULAR, HUMAN	? unclear	Mechanistic	DGIdb
DIDANOSINE	? unclear	Mechanistic	DGIdb
5,7-DIHYDROXY-4-METHYLCOUMARIN	? unclear	Mechanistic	DGIdb
SOBLIDOTIN	? unclear	Mechanistic	DGIdb
STAVUDINE	? unclear	Mechanistic	DGIdb
CISPLATIN	? unclear	Mechanistic	DGIdb
MEROPENEM ANHYDROUS	? unclear	Mechanistic	DGIdb
AMPHOTERICIN B LIPOSOMAL	? unclear	Mechanistic	DGIdb
MIDAZOLAM HYDROCHLORIDE	? unclear	Mechanistic	DGIdb
RIFAMPIN	? unclear	Mechanistic	DGIdb
AVX-470	? unclear	Mechanistic	DGIdb
KETOROLAC TROMETHAMINE	? unclear	Mechanistic	DGIdb
PRAZOSIN HYDROCHLORIDE	? unclear	Mechanistic	DGIdb
RISPERIDONE	? unclear	Mechanistic	DGIdb
BENZO[E]PYRENE	? unclear	Mechanistic	DGIdb
ETHAMBUTOL HYDROCHLORIDE	? unclear	Mechanistic	DGIdb
REMTOLUMAB	↓ inhibits	Mechanistic	DGIdb
SPIRONOLACTONE	? unclear	Mechanistic	DGIdb
OMEPRAZOLE	? unclear	Mechanistic	DGIdb
CARBOPLATIN	? unclear	Mechanistic	DGIdb
MITOMYCIN C ANALOG KW-2149	? unclear	Mechanistic	DGIdb
NAFAMOSTAT	? unclear	Mechanistic	DGIdb
ABBV-3373	~ modulates	Mechanistic	DGIdb
BACILLUS CALMETTE-GUERIN ANTIGEN	? unclear	Mechanistic	DGIdb

Showing top 40 of 287 agents ranked by evidence tier.

Clinical Trials

Drug, biologic and supplement trials (treatment or prevention) from ClinicalTrials.gov whose main condition is Lyme Disease / Post-Treatment Lyme Disease Syndrome (PTLDS): recruiting, active or completed, most recently updated first. Data retrieved 2026-10-28.

Ceftriaxone Pulse Dose for Post-Treatment Lyme Disease Recruiting

NCT06611111 Phase: Early 1 Started: 2025-02-03

The goal of this clinical trial is to learn if an FDA approved drug, Ceftriaxone, given intermittently, can treat people between 18 and 75 years old with a history of Lyme disease, who are still experiencing persistent or returning symptoms after they have completed treatment. The main questions it ...

Effects of Psilocybin in Post-Treatment Lyme Disease Completed

NCT05305105 Phase: 1 Started: 2022-07-01

This study will examine the effects of psilocybin on Lyme disease symptom burden and quality of life in people with Post-Treatment Lyme Disease (PTLD).

Treating Post-Lyme Disease Syndrome With Acetogenins Completed

NCT04078841 Phase: 1/2 Started: 2019-07-01

To access the effectiveness of Acetogenins in treating Post-Lyme Disease Syndrome (PLDS).

Phase 2 Study Of VLA15, A Vaccine Candidate Against Lyme Borreliosis, In A Healthy Pediatric And Adult Study Population Completed

NCT04801420 Phase: 2 Started: 2021-03-08

VLA15-221 is a Phase 2 study, which will be conducted in two parts: Main Study Phase (Part A) and Booster Phase (Part B). The study will compare the safety and immunogenicity of two different primary immunization schedules applying three (Month 0-2-6) or two (Month 0- 6) vaccinations. Within the stu...

A Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1982 to Prevent Lyme Disease in Healthy Participants (18 to 70 Years of Age) Active Not Recruiting

NCT07561294 Phase: 2 Started: 2026-04-29

This clinical study will evaluate the safety, reactogenicity, and immunogenicity of monovalent mRNA-1982, a messenger ribonucleic acid (mRNA) vaccine to prevent Lyme disease in healthy adults aged 18 to 70 years old.

A Study to Evaluate the Safety and Immunogenicity of mRNA-1975 and mRNA-1982 Against Lyme Disease in Participants 18 Through 70 Years of Age Completed

NCT05975099 Phase: 1/2 Started: 2023-07-26

The purpose of this study is to evaluate the safety and immunogenicity in parallel of heptavalent mRNA-1975 and monovalent mRNA-1982 against Lyme disease in healthy adult participants.

A Study to Evaluate Safety and Efficacy of TP-05 in Healthy Participants With Tick Exposure Active Not Recruiting

NCT07562087 Phase: 2 Started: 2026-03-09

This study is designed to evaluate the safety, tolerability, and pharmacokinetics of TP05 administered orally to healthy adult participants.

An Efficacy, Safety, Tolerability, Immunogenicity, and Lot-Consistency Clinical Trial of a 6-Valent OspA-Based Lyme Disease Vaccine (VLA15) Completed

NCT05477524 Phase: 3 Started: 2022-08-04

The main purpose of this clinical study is to evaluate a 6-valent OspA-based Lyme disease vaccine (VLA15) for prevention of Lyme disease within North America and Europe. Approximately 9,400 healthy participants (this number excludes participants from 8 sites which were terminated for quality issues)...

A Study to Learn About Different Dosing Schedules of a Lyme Disease Vaccine in Healthy Adults Active Not Recruiting

NCT07226882 Phase: 3 Started: 2025-11-19

The purpose of this study is to learn about the safety and effects of the Lyme disease vaccine (called VLA15) when given at different time points. This study is seeking participants who: * are generally healthy and between 18 and 44 years of age, * have never had a vaccine for Lyme disease before, *...

A Study to Learn About the Safety, Tolerability, and Immunogenicity of a Fifth Dose of 6-Valent OspA-Based Lyme Disease Vaccine Recruiting

NCT07500506 Phase: 3 Started: 2026-04-08

The purpose of this study is to learn about the safety effects of the Lyme disease vaccine (called VLA15), and its ability to protect people from Lyme disease after a 5th dose of the vaccine. This study is seeking participants who: * are generally healthy and 7 years of age and older, * have already...

Alternative Schedule Study For VLA15, a Vaccine Candidate Against Lyme Borreliosis Completed

NCT03970733 Phase: 2 Started: 2019-07-01

In the Main Study Phase a total of 246 subjects were randomized 2:2:1 into three treatment groups to receive either VLA15 with Alum (lower or higher dose) or Placebo. Main Study Phase vaccinations were administered as intramuscular injections on Day 1, Day 57 and Day 180. In the Booster Phase subjec...

Study Assessing the Safety, Immunogenicity and Dose Response of VLA15, A New Vaccine Candidate Against Lyme Borreliosis Completed

NCT03010228 Phase: 1 Started: 2017-01-31

Observer-blind, partially randomized, multi-center dose escalation Phase I study in healthy adults below 40 years of age. 180 subjects will be enrolled in 6 treatment groups (different doses; different formulation: with/without adjuvant); vaccinations will be given I.M.(intramuscular) into the delto...

Immunogenicity and Safety Study of a Vaccine Against Lyme Borreliosis, in Healthy Adults Aged 18 to 65 Years. Randomized, Controlled, Observer-blind Phase 2 Study. Completed

NCT03769194 Phase: 2 Started: 2018-12-17

This is a randomized, observer-blind, placebo controlled, multicenter Phase 2 study conducted in two study phases: a run-in phase and a main study phase. The study was investigated 3 doses of a multivalent OspA (Outer Surface Protein A) based Lyme vaccine (VLA15) in healthy adults aged 18 to 65 year...

A Novel Nutraceutical to Combat Post-Lyme Disease Syndrome Completed

NCT04141969 Phase: 2/3 Started: 2019-11-29

This study will determine the effectiveness of a nutraceutical in treating the lingering effects of Lyme Disease after antibiotic treatment.

Agents Found By Disease-Level Search

Searched directly from “Lyme Disease / Post-Treatment Lyme Disease Syndrome (PTLDS)” via ClinicalTrials.gov interventions and Open Targets' disease→drug data — independent of the 10-gene target panel above. This surfaces agents whose mechanism doesn't route through a curated gene (combination therapies, standard-of-care drugs, targets outside the panel).

44 agents shown (approved or with trial evidence) — 44 not found by the gene-target search above.

DoxycyclineNOT in gene-target list

Phase 3 · 12 trials · source: ClinicalTrials.gov, Open Targets
NCT02553473 NCT01475708 NCT01368341

VLA15NOT in gene-target list

· 7 trials · source: ClinicalTrials.gov
NCT03970733 NCT03769194 NCT05477524

ceftriaxoneNOT in gene-target list

Phase 3 · 5 trials · source: ClinicalTrials.gov, Open Targets
NCT00000938 NCT00001101 NCT00037479

Multivalent recombinant OspA Lyme Borreliosis VaccineNOT in gene-target list

· 3 trials · source: ClinicalTrials.gov
NCT01504347 NCT01504347 NCT01504347

Controls without a history of lyme disease.NOT in gene-target list

· 2 trials · source: ClinicalTrials.gov
NCT03153267 NCT03337932

blood drawNOT in gene-target list

· 2 trials · source: ClinicalTrials.gov
NCT05036707 NCT02446626

AntibioticsNOT in gene-target list

· 2 trials · source: ClinicalTrials.gov
NCT00000937 NCT03371563

mRNA-1982NOT in gene-target list

· 2 trials · source: ClinicalTrials.gov
NCT05975099 NCT07561294

IFA, LIAISONNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT03798704

taVNSNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT05776251

rk28 ICTNOT in gene-target list