Biomarker & Intervention Discovery

Alpha-1 Antitrypsin Deficiency (AATD)

This page lists 9 druggable gene targets, 53 approved or trial-tested drug candidates and 15 recent clinical trials for Alpha-1 Antitrypsin Deficiency (AATD), with each agent ranked by the strength of its evidence (clinical, mechanistic or correlative). Candidates include existing drugs that could be repurposed. Sources are linked so you can check every claim.

Spontaneous remissionProgressive lung and liver disease; ZZ genotype: FEV1 decline accelerated (80-100 mL/year vs 30 mL/year in…
Best-intervention remissionAlpha-1 augmentation therapy (IV human AAT): slows CT-measured emphysema progression by 34% (RAPID trial); smoking…
Gap sizeVery large — only 5-10% of AATD individuals are diagnosed; augmentation therapy reduces CT progression but functional…
Primary barrieraccess + practice (underdiagnosis)
Full remission profile →
Research Tracker Chronic Disease Interventions Alpha-1 Antitrypsin Deficiency (AATD)

Remission & chronicity

Spontaneous remission
Progressive lung and liver disease; ZZ genotype: FEV1 decline accelerated (80-100 mL/year vs 30 mL/year in non-smokers); liver cirrhosis progressive; no spontaneous resolution without augmentation therapy
Best-intervention remission
Alpha-1 augmentation therapy (IV human AAT): slows CT-measured emphysema progression by 34% (RAPID trial); smoking cessation: most important modifiable factor (reduces FEV1 decline to near-normal rate); fazirsiran (RNAi targeting hepatic AAT production): 83% reduction in Z-AAT liver accumulation
Gap size
Very large — only 5-10% of AATD individuals are diagnosed; augmentation therapy reduces CT progression but functional benefit debated; liver disease has no approved disease-modifying therapy
Primary barrier
access + practice (underdiagnosis)
AATD is misdiagnosed as COPD or asthma for a mean of 5-7 years; spirometry for COPD should trigger AATD testing but this is rarely done; fazirsiran (RNAi) reduces hepatic Z-protein accumulation — Phase 3 underway for liver disease; augmentation therapy is IV every 4 weeks lifelong (~$100K/year)

Biomarker Targets & Therapeutic Agents

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

CTSC 159CTSG 197CXCR2 224ELANE 207MMP12 190MMP9 220PRTN3 49SERPINA1 2TGFB1 62

CTSC

UniProt Ensembl DGIdb Open Targets
Therapeutic Agent Effect Direction Evidence Tier Potency Source
BRENSOCATIB ↓ inhibits Mechanistic 2.512 nM (Kd) DGIdb
PROGESTERONE ? unclear Mechanistic DGIdb
ICATCXPZ-01 ↓ inhibits Mechanistic DGIdb
PENTOSAN POLYSULFATE ? unclear Mechanistic DGIdb
GSK2793660 ↓ inhibits Mechanistic DGIdb
COMPOUND 3D [PMID: 3941405] ↓ inhibits Mechanistic DGIdb
HSK31858 ↓ inhibits Mechanistic DGIdb
CALCIUM GLUCONATE ? unclear Mechanistic DGIdb
CHEMBL12954 ↓ inhibits Mechanistic 2700.0 nM (Ki) ChEMBL
CHEMBL212514 ↓ inhibits Mechanistic 9637.0 nM (IC50) ChEMBL
CHEMBL377768 ↓ inhibits Mechanistic 6296.0 nM (IC50) ChEMBL
CHEMBL212521 ↓ inhibits Mechanistic 13.0 nM (IC50) ChEMBL
CHEMBL209998 ↓ inhibits Mechanistic 96.0 nM (IC50) ChEMBL
CHEMBL211388 ↓ inhibits Mechanistic 137.0 nM (IC50) ChEMBL
CHEMBL212523 ↓ inhibits Mechanistic 822.0 nM (IC50) ChEMBL
CHEMBL439145 ↓ inhibits Mechanistic 172.0 nM (IC50) ChEMBL
CHEMBL379542 ↓ inhibits Mechanistic 4787.0 nM (IC50) ChEMBL
CHEMBL230473 ↓ inhibits Mechanistic 1727.0 nM (IC50) ChEMBL
CHEMBL230478 ↓ inhibits Mechanistic 191.0 nM (IC50) ChEMBL
CHEMBL390475 ↓ inhibits Mechanistic 403.0 nM (IC50) ChEMBL
CHEMBL230474 ↓ inhibits Mechanistic 29.0 nM (IC50) ChEMBL
CHEMBL390643 ↓ inhibits Mechanistic 606.0 nM (IC50) ChEMBL
CHEMBL390474 ↓ inhibits Mechanistic 18.0 nM (IC50) ChEMBL
CHEMBL448143 ↓ inhibits Mechanistic 51.0 nM (IC50) ChEMBL
CHEMBL516292 ↓ inhibits Mechanistic 14.0 nM (IC50) ChEMBL
E-64 ↓ inhibits Mechanistic 770.0 nM (IC50) ChEMBL
CHEMBL518284 ↓ inhibits Mechanistic 450.0 nM (IC50) ChEMBL
CHEMBL450997 ↓ inhibits Mechanistic 1.0 nM (IC50) ChEMBL
CHEMBL1162478 ↓ inhibits Mechanistic 790.0 nM (IC50) ChEMBL
CHEMBL461619 ↓ inhibits Mechanistic 10000.0 nM (Ki) ChEMBL
CHEMBL514348 ↓ inhibits Mechanistic 70.0 nM (IC50) ChEMBL
CHEMBL486232 ↓ inhibits Mechanistic 2600.0 nM (IC50) ChEMBL
CHEMBL567341 ↓ inhibits Mechanistic 34.67 nM (IC50) ChEMBL
CHEMBL578159 ↓ inhibits Mechanistic 6918.31 nM (IC50) ChEMBL
CHEMBL567134 ↓ inhibits Mechanistic 588.84 nM (IC50) ChEMBL
GRASSYSTATIN A ↓ inhibits Mechanistic 10000.0 nM (IC50) ChEMBL
CHEMBL1081329 ↓ inhibits Mechanistic 200.0 nM (IC50) ChEMBL
CHEMBL1082054 ↓ inhibits Mechanistic 630.0 nM (IC50) ChEMBL
CHEMBL1079350 ↓ inhibits Mechanistic 1580.0 nM (IC50) ChEMBL
CHEMBL1079351 ↓ inhibits Mechanistic 330.0 nM (IC50) ChEMBL

Showing top 40 of 159 agents ranked by evidence tier.

CTSG

UniProt Ensembl DGIdb Open Targets
Therapeutic Agent Effect Direction Evidence Tier Potency Source
COMPOUND 4G [PMID: 22595175] ↓ inhibits Mechanistic DGIdb
LYMPHOKINE-ACTIVATED KILLER CELLS ? unclear Mechanistic DGIdb
COMPOUND 1 [PMID: 11425539] ↓ inhibits Mechanistic DGIdb
RECOMBINANT INTERFERON ? unclear Mechanistic DGIdb
JNJ-10311795 ? unclear Mechanistic DGIdb
SULFONE ANTI-INFECTIVE AGENT ? unclear Mechanistic DGIdb
MANNITOL ? unclear Mechanistic DGIdb
ALOXISTATIN ↓ inhibits Mechanistic 1100.0 nM (IC50) DGIdb
RECOMBINANT TUMOR NECROSIS FACTOR FAMILY PROTEIN ? unclear Mechanistic DGIdb
TNF-ALPHA ? unclear Mechanistic DGIdb
VITAMIN K ? unclear Mechanistic DGIdb
BORTEZOMIB ↓ inhibits Mechanistic 630.0 nM (Ki) ChEMBL
CHEMBL296771 ↓ inhibits Mechanistic 2.3 nM (IC50) ChEMBL
CHEMBL47394 ↓ inhibits Mechanistic 0.39 nM (IC50) ChEMBL
CHEMBL298276 ↓ inhibits Mechanistic 740.0 nM (IC50) ChEMBL
CHEMBL213783 ↓ inhibits Mechanistic 1500.0 nM (Ki) ChEMBL
CHEMBL3349045 ↓ inhibits Mechanistic 3.9 nM (Ki) ChEMBL
CHEMBL291261 ↓ inhibits Mechanistic 44.1 nM (Ki) ChEMBL
CHEMBL418050 ↓ inhibits Mechanistic 0.174 nM (Ki) ChEMBL
CHEMBL2448441 ↓ inhibits Mechanistic 0.437 nM (Ki) ChEMBL
CHEMBL36744 ↓ inhibits Mechanistic 25.3 nM (Ki) ChEMBL
CHEMBL290577 ↓ inhibits Mechanistic 0.916 nM (Ki) ChEMBL
CHEMBL287918 ↓ inhibits Mechanistic 14.3 nM (Ki) ChEMBL
CHEMBL291026 ↓ inhibits Mechanistic 3.74 nM (Ki) ChEMBL
CHEMBL288176 ↓ inhibits Mechanistic 3.85 nM (Ki) ChEMBL
CHEMBL285285 ↓ inhibits Mechanistic 0.187 nM (Ki) ChEMBL
CHEMBL412452 ↓ inhibits Mechanistic 2200.0 nM (IC50) ChEMBL
CHEMBL304729 ↓ inhibits Mechanistic 230.0 nM (IC50) ChEMBL
CHEMBL71362 ↓ inhibits Mechanistic 1500.0 nM (IC50) ChEMBL
CHEMBL308215 ↓ inhibits Mechanistic 220.0 nM (IC50) ChEMBL
CHEMBL303908 ↓ inhibits Mechanistic 26000.0 nM (IC50) ChEMBL
CHEMBL68428 ↓ inhibits Mechanistic 4800.0 nM (IC50) ChEMBL
CHEMBL303431 ↓ inhibits Mechanistic 4100.0 nM (IC50) ChEMBL
CHEMBL69096 ↓ inhibits Mechanistic 4800.0 nM (IC50) ChEMBL
CHEMBL67947 ↓ inhibits Mechanistic 4500.0 nM (IC50) ChEMBL
CHEMBL412582 ↓ inhibits Mechanistic 7000.0 nM (IC50) ChEMBL
CHEMBL68585 ↓ inhibits Mechanistic 4500.0 nM (IC50) ChEMBL
CHEMBL69991 ↓ inhibits Mechanistic 700.0 nM (IC50) ChEMBL
CHEMBL69611 ↓ inhibits Mechanistic 2000.0 nM (IC50) ChEMBL
CHEMBL273334 ↓ inhibits Mechanistic 3700.0 nM (IC50) ChEMBL

Showing top 40 of 197 agents ranked by evidence tier.

CXCR2

UniProt Ensembl DGIdb Open Targets
Therapeutic Agent Effect Direction Evidence Tier Potency Source
CANOCTAKIN ? unclear Mechanistic DGIdb
[125I]CXCL8 (HUMAN) ↑ activates Mechanistic DGIdb
REPARIXIN ~ modulates Mechanistic DGIdb
CXCL5 ↑ activates Mechanistic DGIdb
MECHLORETHAMINE HYDROCHLORIDE ? unclear Mechanistic DGIdb
[125I]CXCL5 (HUMAN) ↑ activates Mechanistic DGIdb
SX-682 ↓ inhibits Mechanistic DGIdb
VIMNERIXIN ? unclear Mechanistic DGIdb
[125I]CXCL7 (HUMAN) ↑ activates Mechanistic DGIdb
VCXCL1 ↑ activates Mechanistic DGIdb
HIV-1 MATRIX PROTEIN P17 ↑ activates Mechanistic DGIdb
NAVARIXIN ↓ inhibits Mechanistic DGIdb
AZD5069 ↓ inhibits Mechanistic DGIdb
DANIRIXIN ↓ inhibits Mechanistic DGIdb
CXCL8 ↑ activates Mechanistic DGIdb
D-ALPHA-TOCOPHEROL ? unclear Mechanistic DGIdb
CXCL2 ↑ activates Mechanistic DGIdb
CYCLOPHOSPHAMIDE ANHYDROUS ? unclear Mechanistic DGIdb
GENISTEIN ? unclear Mechanistic DGIdb
AZD-5122 ? unclear Mechanistic DGIdb
CLOTRIMAZOLE ? unclear Mechanistic DGIdb
NSC 157449 ↓ inhibits Mechanistic DGIdb
IBUPROFEN, SODIUM SALT ? unclear Mechanistic DGIdb
[125I]CXCL1 (HUMAN) ↑ activates Mechanistic DGIdb
SX-517 ↓ inhibits Mechanistic DGIdb
SB 225002 ↓ inhibits Mechanistic DGIdb
CXCL6 ↑ activates Mechanistic DGIdb
CXCL3 ↑ activates Mechanistic DGIdb
CXCL1 ↑ activates Mechanistic DGIdb
ACETYLCYSTEINE ? unclear Mechanistic DGIdb
LADARIXIN ~ modulates Mechanistic DGIdb
BEVACIZUMAB ? unclear Mechanistic DGIdb
CXCL7 ↑ activates Mechanistic DGIdb
ELUBRIXIN ↓ inhibits Mechanistic DGIdb
NAVARIXIN ANHYDROUS ? unclear Mechanistic 2.6 nM (IC50) Open Targets
CHEMBL25573 ↓ inhibits Mechanistic 200.0 nM (IC50) ChEMBL
CHEMBL27863 ↓ inhibits Mechanistic 25.0 nM (IC50) ChEMBL
CHEMBL283736 ↓ inhibits Mechanistic 860.0 nM (IC50) ChEMBL
CHEMBL280711 ↓ inhibits Mechanistic 320.0 nM (IC50) ChEMBL
CHEMBL27446 ↓ inhibits Mechanistic 22.0 nM (IC50) ChEMBL

Showing top 40 of 224 agents ranked by evidence tier.

ELANE

UniProt Ensembl DGIdb Open Targets
Therapeutic Agent Effect Direction Evidence Tier Potency Source
LONODELESTAT ? unclear Mechanistic DGIdb
POSTSTATIN ↓ inhibits Mechanistic DGIdb
SIVELESTAT SODIUM ? unclear Mechanistic DGIdb
EPIGALLOCATECHIN GALLATE ? unclear Mechanistic DGIdb
DEPELESTAT ? unclear Mechanistic DGIdb
CHF6333 ↓ inhibits Mechanistic DGIdb
COMPOUND 10L [PMID: 24556381] ↓ inhibits Mechanistic DGIdb
ALPHA 1-ANTITRYPSIN ↓ inhibits Mechanistic DGIdb
NICOTINE POLACRILEX ? unclear Mechanistic DGIdb
COMPOUND 10F [PMID: 24556381] ↓ inhibits Mechanistic DGIdb
TIPRELESTAT ? unclear Mechanistic DGIdb
BAY-678 ↓ inhibits Mechanistic DGIdb
SYMPLOSTATIN 5 ? unclear Mechanistic DGIdb
COMPOUND 4G [PMID: 22595175] ↓ inhibits Mechanistic DGIdb
NIFEDIPINE ? unclear Mechanistic DGIdb
ELAFIN ? unclear Mechanistic DGIdb
ALVELESTAT ↓ inhibits Mechanistic DGIdb
ERDOSTEINE ? unclear Mechanistic DGIdb
CHEMBL:CHEMBL310871 ? unclear Mechanistic DGIdb
.ALPHA.1-PROTEINASE INHIBITOR HUMAN ↓ inhibits Mechanistic DGIdb
SIVELESTAT ↓ inhibits Mechanistic DGIdb
CHEMBL314218 ↓ inhibits Mechanistic 0.03 nM (Ki) ChEMBL
CHEMBL274085 ↓ inhibits Mechanistic 2.7 nM (Ki) ChEMBL
CHEMBL329376 ↓ inhibits Mechanistic 31.0 nM (Ki) ChEMBL
CHEMBL543416 ↓ inhibits Mechanistic 0.014 nM (Ki) ChEMBL
CHEMBL51377 ↓ inhibits Mechanistic 102.0 nM (Ki) ChEMBL
CHEMBL432049 ↓ inhibits Mechanistic 0.17 nM (Ki) ChEMBL
CHEMBL89299 ↓ inhibits Mechanistic 8.0 nM (Ki) ChEMBL
CHEMBL95813 ↓ inhibits Mechanistic 300.0 nM (IC50) ChEMBL
CHEMBL330647 ↓ inhibits Mechanistic 25000.0 nM (IC50) ChEMBL
CHEMBL91944 ↓ inhibits Mechanistic 0.06 nM (Ki) ChEMBL
CHEMBL318052 ↓ inhibits Mechanistic 36000.0 nM (IC50) ChEMBL
CHEMBL319173 ↓ inhibits Mechanistic 1200.0 nM (IC50) ChEMBL
CHEMBL2368616 ↓ inhibits Mechanistic 0.31 nM (Ki) ChEMBL
CHEMBL554013 ↓ inhibits Mechanistic 1.73 nM (Ki) ChEMBL
CHEMBL90730 ↓ inhibits Mechanistic 26.0 nM (Ki) ChEMBL
CHEMBL421162 ↓ inhibits Mechanistic 1.0 nM (Ki) ChEMBL
CHEMBL88117 ↓ inhibits Mechanistic 8.0 nM (Ki) ChEMBL
CHEMBL542949 ↓ inhibits Mechanistic 0.16 nM (Ki) ChEMBL
CHEMBL99558 ↓ inhibits Mechanistic 3000.0 nM (IC50) ChEMBL

Showing top 40 of 207 agents ranked by evidence tier.

MMP12

UniProt Ensembl DGIdb Open Targets
Therapeutic Agent Effect Direction Evidence Tier Potency Source
RXP470.1 ↓ inhibits Mechanistic DGIdb
AZD-1236 ↓ inhibits Mechanistic DGIdb
ILOMASTAT ↓ inhibits Mechanistic 13.0 nM (IC50) DGIdb
AZD1236 ↓ inhibits Mechanistic DGIdb
ADERMASTAT ? unclear Mechanistic DGIdb
BAY-7598 ↓ inhibits Mechanistic DGIdb
ACETAZOLAMIDE ? unclear Mechanistic DGIdb
CTS-1027 ↓ inhibits Mechanistic DGIdb
COMPOUND 1 [PMID: 24900526] ↓ inhibits Mechanistic DGIdb
AZD6605 ↓ inhibits Mechanistic DGIdb
DEFEROXAMINE ? unclear Mechanistic DGIdb
COMPOUND 20 [PMID: 22153340] ↓ inhibits Mechanistic DGIdb
MARIMASTAT ↓ inhibits Mechanistic DGIdb
CAPTOPRIL ? unclear Mechanistic DGIdb
NEOVASTAT ↓ inhibits Mechanistic DGIdb
TP0556351 ↓ inhibits Mechanistic DGIdb
ZILEUTON ? unclear Mechanistic DGIdb
COMPOUND 5 [PMID: 24900526] ↓ inhibits Mechanistic DGIdb
CHEMBL1788203 ↓ inhibits Mechanistic 42.0 nM (IC50) ChEMBL
CHEMBL263501 ↓ inhibits Mechanistic 12.0 nM (IC50) ChEMBL
CHEMBL2092878 ↓ inhibits Mechanistic 9.0 nM (IC50) ChEMBL
CHEMBL77258 ↓ inhibits Mechanistic 14.0 nM (IC50) ChEMBL
CHEMBL78001 ↓ inhibits Mechanistic 13.0 nM (IC50) ChEMBL
CHEMBL148406 ↓ inhibits Mechanistic 191.0 nM (IC50) ChEMBL
CHEMBL147882 ↓ inhibits Mechanistic 29.0 nM (IC50) ChEMBL
CHEMBL148171 ↓ inhibits Mechanistic 65.0 nM (IC50) ChEMBL
CHEMBL424130 ↓ inhibits Mechanistic 170.0 nM (IC50) ChEMBL
CHEMBL147881 ↓ inhibits Mechanistic 57.0 nM (IC50) ChEMBL
CHEMBL148214 ↓ inhibits Mechanistic 20.0 nM (IC50) ChEMBL
CHEMBL356124 ↓ inhibits Mechanistic 7689.0 nM (IC50) ChEMBL
CHEMBL358539 ↓ inhibits Mechanistic 57.0 nM (IC50) ChEMBL
CHEMBL147489 ↓ inhibits Mechanistic 59.0 nM (IC50) ChEMBL
CHEMBL147604 ↓ inhibits Mechanistic 931.0 nM (IC50) ChEMBL
CHEMBL146718 ↓ inhibits Mechanistic 72.0 nM (IC50) ChEMBL
CHEMBL146289 ↓ inhibits Mechanistic 421.0 nM (IC50) ChEMBL
CHEMBL431680 ↓ inhibits Mechanistic 390.0 nM (Ki) ChEMBL
CHEMBL325163 ↓ inhibits Mechanistic 2000.0 nM (Ki) ChEMBL
CHEMBL114878 ↓ inhibits Mechanistic 35.0 nM (Ki) ChEMBL
CHEMBL116944 ↓ inhibits Mechanistic 3.5 nM (IC50) ChEMBL
CHEMBL118497 ↓ inhibits Mechanistic 2.6 nM (IC50) ChEMBL

Showing top 40 of 190 agents ranked by evidence tier.

MMP9

UniProt Ensembl DGIdb Open Targets
Therapeutic Agent Effect Direction Evidence Tier Potency Source
MARIMASTAT ↓ inhibits Mechanistic 1.5 nM (IC50) DGIdb
TOZULERISTIDE ? unclear Mechanistic DGIdb
CTS-1027 ↓ inhibits Mechanistic 3.0 nM (IC50) DGIdb
SHARK CARTILAGE EXTRACT AE-941 ? unclear Mechanistic DGIdb
ILOMASTAT ↓ inhibits Mechanistic DGIdb
CURCUMIN PYRAZOLE ? unclear Mechanistic DGIdb
HYDRALAZINE ? unclear Mechanistic DGIdb
SL422 ↓ inhibits Mechanistic DGIdb
BEVACIZUMAB ? unclear Mechanistic DGIdb
METHYLDOPA ANHYDROUS ? unclear Mechanistic DGIdb
TST10088 ? unclear Mechanistic DGIdb
ANDECALIXIMAB ? unclear Mechanistic DGIdb
SB-3CT ↓ inhibits Mechanistic DGIdb
COMPOUND 29E [PMID: 23631440] ↓ inhibits Mechanistic DGIdb
NIFEDIPINE ? unclear Mechanistic DGIdb
ANTIHYPERTENSIVE AGENT ? unclear Mechanistic DGIdb
S-3304 ? unclear Mechanistic 23.0 nM (IC50) DGIdb
AZD-1236 ↓ inhibits Mechanistic DGIdb
INCYCLINIDE ? unclear Mechanistic DGIdb
CARBOXYLATED GLUCOSAMINE ? unclear Mechanistic DGIdb
TP0556351 ↓ inhibits Mechanistic DGIdb
CELECOXIB ? unclear Mechanistic DGIdb
ULINASTATIN ? unclear Mechanistic DGIdb
COMPOUND 1A [PMID: 15055993] ↓ inhibits Mechanistic DGIdb
AZD6605 ↓ inhibits Mechanistic DGIdb
AZD1236 ↓ inhibits Mechanistic DGIdb
CGS-27023A ↓ inhibits Mechanistic 9.0 nM (IC50) DGIdb
CURCUMIN ? unclear Mechanistic DGIdb
(R)-ND-336 ↓ inhibits Mechanistic DGIdb
NEOVASTAT ↓ inhibits Mechanistic DGIdb
REBIMASTAT ↓ inhibits Mechanistic DGIdb
PRINOMASTAT ? unclear Mechanistic 0.2 nM (IC50) DGIdb
DP-B99 ? unclear Mechanistic DGIdb
DEMETHYLWEDELOLACTONE ? unclear Mechanistic DGIdb
CHEMBL435271 ↓ inhibits Mechanistic 5.0 nM (Ki) ChEMBL
CHEMBL80814 ↓ inhibits Mechanistic 34.0 nM (IC50) ChEMBL
CHEMBL276119 ↓ inhibits Mechanistic 9.0 nM (IC50) ChEMBL
CHEMBL78934 ↓ inhibits Mechanistic 20.0 nM (IC50) ChEMBL
CHEMBL78369 ↓ inhibits Mechanistic 3.0 nM (IC50) ChEMBL
CHEMBL167278 ↓ inhibits Mechanistic 2.0 nM (Ki) ChEMBL

Showing top 40 of 220 agents ranked by evidence tier.

PRTN3

UniProt Ensembl DGIdb Open Targets
Therapeutic Agent Effect Direction Evidence Tier Potency Source
ELAFIN ? unclear Mechanistic DGIdb
COMPOUND 4G [PMID: 22595175] ↓ inhibits Mechanistic DGIdb
AZAPRO-3 ↓ inhibits Mechanistic DGIdb
COMPOUND 11 [PMID: 29442501] ↓ inhibits Mechanistic DGIdb
GM-CSF ? unclear Mechanistic DGIdb
MYCOPHENOLATE MOFETIL ? unclear Mechanistic DGIdb
TIPRELESTAT ? unclear Mechanistic DGIdb
CHEMBL2029554 ↓ inhibits Mechanistic 12800.0 nM (IC50) ChEMBL
CHEMBL2029556 ↓ inhibits Mechanistic 1400.0 nM (IC50) ChEMBL
CHEMBL2029557 ↓ inhibits Mechanistic 14500.0 nM (IC50) ChEMBL
CHEMBL2029559 ↓ inhibits Mechanistic 5000.0 nM (IC50) ChEMBL
CHEMBL3093814 ↓ inhibits Mechanistic 47500.0 nM (IC50) ChEMBL
CHEMBL3093815 ↓ inhibits Mechanistic 5900.0 nM (IC50) ChEMBL
CHEMBL3359765 ↓ inhibits Mechanistic 1910.0 nM (IC50) ChEMBL
CHEMBL3359767 ↓ inhibits Mechanistic 10380.0 nM (IC50) ChEMBL
PHENYLMETHYLSULFONYLFLUORIDE ↓ inhibits Mechanistic 19230.0 nM (IC50) ChEMBL
CHEMBL3398160 ↓ inhibits Mechanistic 4940.0 nM (IC50) ChEMBL
CHEMBL3398156 ↓ inhibits Mechanistic 3910.0 nM (IC50) ChEMBL
CHEMBL3398155 ↓ inhibits Mechanistic 3020.0 nM (IC50) ChEMBL
CHEMBL3398154 ↓ inhibits Mechanistic 2050.0 nM (IC50) ChEMBL
CHEMBL3398153 ↓ inhibits Mechanistic 530.0 nM (IC50) ChEMBL
CHEMBL3398152 ↓ inhibits Mechanistic 2370.0 nM (IC50) ChEMBL
CHEMBL3398151 ↓ inhibits Mechanistic 610.0 nM (IC50) ChEMBL
CHEMBL3398150 ↓ inhibits Mechanistic 1730.0 nM (IC50) ChEMBL
CHEMBL3398149 ↓ inhibits Mechanistic 2500.0 nM (IC50) ChEMBL
CHEMBL3398148 ↓ inhibits Mechanistic 220.0 nM (IC50) ChEMBL
CHEMBL3398147 ↓ inhibits Mechanistic 2050.0 nM (IC50) ChEMBL
CHEMBL3398146 ↓ inhibits Mechanistic 2310.0 nM (IC50) ChEMBL
CHEMBL3398145 ↓ inhibits Mechanistic 360.0 nM (IC50) ChEMBL
CHEMBL3398144 ↓ inhibits Mechanistic 1090.0 nM (IC50) ChEMBL
CHEMBL3398143 ↓ inhibits Mechanistic 470.0 nM (IC50) ChEMBL
CHEMBL3398164 ↓ inhibits Mechanistic 310.0 nM (IC50) ChEMBL
CHEMBL3398165 ↓ inhibits Mechanistic 610.0 nM (IC50) ChEMBL
SIVELESTAT ↓ inhibits Mechanistic 340.0 nM (IC50) ChEMBL
CHEMBL4071346 ↓ inhibits Mechanistic 5.4 nM (Ki) ChEMBL
CHEMBL4085013 ↓ inhibits Mechanistic 21.0 nM (Ki) ChEMBL
CHEMBL4102959 ↓ inhibits Mechanistic 3600.0 nM (Ki) ChEMBL
CHEMBL4104474 ↓ inhibits Mechanistic 54000.0 nM (IC50) ChEMBL
CHEMBL4470455 ↓ inhibits Mechanistic 51.0 nM (Ki) ChEMBL
CHEMBL4469546 ↓ inhibits Mechanistic 245.0 nM (Ki) ChEMBL

Showing top 40 of 49 agents ranked by evidence tier.

SERPINA1

UniProt Ensembl DGIdb Open Targets
Therapeutic Agent Effect Direction Evidence Tier Potency Source
IGMESINE ? unclear Mechanistic DGIdb
ALPHA 1-ANTITRYPSIN ? unclear Mechanistic DGIdb

TGFB1

UniProt Ensembl DGIdb Open Targets
Therapeutic Agent Effect Direction Evidence Tier Potency Source
LY-2382770 ↓ inhibits Mechanistic DGIdb
ETOPOSIDE ? unclear Mechanistic DGIdb
BROXURIDINE ? unclear Mechanistic DGIdb
INOSITOL ? unclear Mechanistic DGIdb
D-ALPHA-TOCOPHEROL ? unclear Mechanistic DGIdb
STREPTOZOCIN ? unclear Mechanistic DGIdb
PROTEASOME INHIBITOR ? unclear Mechanistic DGIdb
FRESOLIMUMAB ↓ inhibits Mechanistic DGIdb
THERAPEUTIC ANDROGEN ? unclear Mechanistic DGIdb
GALUNISERTIB ? unclear Mechanistic DGIdb
TOREMIFENE ? unclear Mechanistic DGIdb
TRETINOIN ? unclear Mechanistic DGIdb
BINTRAFUSP ALFA ~ modulates Mechanistic DGIdb
PIRFENIDONE ? unclear Mechanistic DGIdb
DOXORUBICIN HYDROCHLORIDE ? unclear Mechanistic DGIdb
GOSSYPOL ? unclear Mechanistic DGIdb
EMODIN ? unclear Mechanistic DGIdb
IDOXURIDINE ? unclear Mechanistic DGIdb
HYDROCORTISONE BUTYRATE ? unclear Mechanistic DGIdb
CLADRIBINE ? unclear Mechanistic DGIdb
TG-C ? unclear Mechanistic DGIdb
ASPIRIN ? unclear Mechanistic DGIdb
DISITERTIDE ? unclear Mechanistic DGIdb
RAMIPRIL ? unclear Mechanistic DGIdb
ANTISENSE OLIGONUCLEOTIDES ? unclear Mechanistic DGIdb
HEPARAN SULFATE ? unclear Mechanistic DGIdb
TRIAMCINOLONE ? unclear Mechanistic DGIdb
ESTRADIOL VALERATE ? unclear Mechanistic DGIdb
AMIFOSTINE ANHYDROUS ? unclear Mechanistic DGIdb
KEYHOLE LIMPET HEMOCYANIN ? unclear Mechanistic DGIdb
LUSPATERCEPT ↓ inhibits Mechanistic DGIdb
ATENOLOL ? unclear Mechanistic DGIdb
GALLIUM NITRATE ? unclear Mechanistic DGIdb
ANTIOXIDANT ? unclear Mechanistic DGIdb
FENRETINIDE ? unclear Mechanistic DGIdb
GENISTEIN ? unclear Mechanistic DGIdb
RETINOIC ACID AGENT ? unclear Mechanistic DGIdb
OCTREOTIDE ACETATE ? unclear Mechanistic DGIdb
THERAPEUTIC MELATONIN ? unclear Mechanistic DGIdb
TCDD ? unclear Mechanistic DGIdb

Showing top 40 of 62 agents ranked by evidence tier.

Clinical Trials

Drug, biologic and supplement trials (treatment or prevention) from ClinicalTrials.gov whose main condition is Alpha-1 Antitrypsin Deficiency (AATD): recruiting, active or completed, most recently updated first. Data retrieved 2026-10-28.

A Non-inferiority Pharmacokinetic and Safety/Tolerability Study of Two Different Doses of Weekly SC Alpha1-PI 15% Compared With Corresponding Standard IV Alpha1-PI in Participants With Alpha1-Antitrypsin Deficiency (AATD) Recruiting
NCT07555483 Phase: 3 Started: 2026-05-05

This study is designed to compare two different weekly doses of a medicine called Alpha1-Proteinase Inhibitor given by injection under the skin with the standard doses of the same medicine given through a vein. Adults with Alpha-1 Antitrypsin Deficiency will take part. Participants will be randomly ...

A Study of AIR-001 in Adults With Alpha-1 Antitrypsin Deficiency (AATD) Recruiting
NCT07431112 Phase: 1 Started: 2026-03-17

This is a Phase 1, open-label, single ascending dose (SAD) and multiple dose (MD) study of AIR-001 in participants with alpha-1 antitrypsin deficiency (AATD) due to PiZZ genotype.

A Phase 1b/2a, Open-label Single Ascending Doses and Multiple Ascending Doses Study in Participants With Pi*ZZ AATD Recruiting
NCT06405633 Phase: 1/2 Started: 2024-07-19

The purpose of this open-label study is to assess the safety, tolerability, pharmacodynamics, and pharmacokinetics of WVE-006 in participants with alpha-1 antitrypsin deficiency (AATD) following Period 1 single ascending dose (SAD) and Period 2 multiple ascending doses (MAD), respectively.

Gene Therapy for Alpha 1- Antitrypsin Deficiency Recruiting
NCT06996756 Phase: 1 Started: 2025-02-26

This is a study of gene therapy to treat alpha 1-antitrypsin (AAT) deficiency. This study aims to treat AAT deficiency with a single administration of AAV8hAAT(AVL), a gene therapy that codes for an oxidation resistant form of the AAT protein, which if safe and if efficacious, will protect the lung ...

A Study to Evaluate the Safety and Efficacy of BEAM-302 in Adult Patients With Alpha-1 Antitrypsin Deficiency (AATD) Recruiting
NCT06389877 Phase: 1/2 Started: 2024-06-19

This is a Phase 1/2, multicenter, open-label study conducted in 3 parts (Part A, Part B, and Part C) to evaluate the safety, tolerability, PK/PD, and efficacy of BEAM-302 in adult patients with AATD-associated lung disease and/or liver disease. Parts A and B are designed to evaluate safety and toler...

A Study of TSRA-196 in Adults With PiZZ Alpha-1 Antitrypsin Deficiency (AATD) Recruiting
NCT07227207 Phase: 1/2 Started: 2026-04-21

This is a Phase 1/2, open-label, multi-center, dose escalation (Part 1), dose expansion (Part 2), and single repeat dose (Part 3) study to evaluate the safety, tolerability, efficacy, and PK/PD parameters of TSRA-196 in adults with the PiZZ genotype who have lung and/or liver disease associated with...

Study of BMN 349 Single Dose in PiZZ and PiMZ/MASH Adult Participants Active Not Recruiting
NCT06738017 Phase: 1 Started: 2025-02-21

The goal of this clinical trial is to assess the safety and tolerability of a single oral dose of BMN 349 in participants with PiZZ or PiMZ/MASH. Primary outcome measures include incidence of any adverse events (including serious adverse events, dose limit toxicities, and adverse events of special i...

Long-term, Open-label Study of SAR447537 (INBRX-101) in Adults With Alpha-1 Antitrypsin Deficiency Emphysema Active Not Recruiting
NCT05897424 Phase: 2 Started: 2024-06-20

Phase 2 open label extension study to evaluate SAR447537 (INBRX-101) in adults with AATD emphysema

A Phase 1 Research Study to Evaluate Safety, Tolerability, and Pharmacokinetics of WVE-006 in Healthy Participants With Wild-type AAT Expression (RestorAATion-1) Completed
NCT06186492 Phase: 1 Started: 2023-11-14

This study is the first study in the RestorAATion clinical program. The purpose of this first-in human (FIH), double-blind, randomized, placebo-controlled, single ascending dose (SAD) and multiple-dose Phase 1 study is to assess the safety, tolerability, and pharmacokinetics (PK) of WVE-006 compared...

Study of ARO-AAT in Normal Adult Volunteers Completed
NCT03362242 Phase: 1 Started: 2018-03-12

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single- and multiple-ascending doses of ARO-AAT in healthy adult volunteers.

Safety, Tolerability and Pharmacodynamic Effect of Fazirsiran (TAK-999, ARO-AAT) Completed
NCT03945292 Phase: 2 Started: 2019-08-07

The purpose of AROAAT2001 (SEQUOIA) is to evaluate the safety, efficacy and tolerability of multiple doses of the investigational product, Fazirsiran Injection, administered subcutaneously to participants with alpha-1 antitrypsin deficiency (AATD).

Study of Fazirsiran (TAK-999, ARO-AAT) in Patients With Alpha-1 Antitrypsin Deficiency Associated Liver Disease (AATD) Completed
NCT03946449 Phase: 2 Started: 2019-10-31

The purpose of this study is to evaluate the the safety and efficacy of the investigational product, fazirsiran (TAK-999, ARO-AAT), administered subcutaneously to patients with alpha-1 antitrypsin deficiency associated liver disease (AATD).

Study of YOLT-202 in the Treatment of Alpha-1 Antitrypsin Deficiency (AATD) Active Not Recruiting
NCT07193615 Phase: Early 1 Started: 2025-06-18

This is a single-arm, open-label, single-dose, dose-escalation exploratory study to evaluate the safety and tolerability of a single dose of YOLT-202 in patients with AATD and determine the optimal biologically active dose (OBD) of YOLT-202.

Study of SAR447537 (INBRX-101) Compared to Plasma-derived A1PI Therapy in Adults With AATD Emphysema Completed
NCT05856331 Phase: 2 Started: 2023-10-12

Phase 2 study to compare SAR447537 (INBRX-101) to plasma derived A1PI therapy in adults with AATD emphysema

A Study of KB408 for the Treatment of Alpha-1 Antitrypsin Deficiency Recruiting
NCT06049082 Phase: 1 Started: 2024-02-15

The Sponsor is developing KB408, a replication-defective, non-integrating herpes simplex virus type 1 (HSV-1)-derived vector engineered to deliver functional full-length human SERPINA1 to the airways of people with alpha-1 antitrypsin deficiency (AATD) via nebulization. This study is designed to eva...

Agents Found By Disease-Level Search

Searched directly from “Alpha-1 Antitrypsin Deficiency (AATD)” via ClinicalTrials.gov interventions and Open Targets' disease→drug data — independent of the 9-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).

53 agents shown (approved or with trial evidence) — 52 not found by the gene-target search above.

Alpha1-proteinase inhibitorNOT in gene-target list

· 4 trials · source: ClinicalTrials.gov
NCT01651351 NCT00261833 NCT01370018

Alpha1- proteinase inhibitor [human]

Approved · 4 trials · source: ClinicalTrials.gov, Open Targets
NCT00670007 NCT00295061 NCT00301366

Alpha-1 MPNOT in gene-target list

· 4 trials · source: ClinicalTrials.gov
NCT00295061 NCT02870309 NCT01983241

Fazirsiran InjectionNOT in gene-target list

· 3 trials · source: ClinicalTrials.gov
NCT05899673 NCT06165341 NCT05677971

Blood drawNOT in gene-target list

· 2 trials · source: ClinicalTrials.gov
NCT01810458 NCT01851642

SAR447537NOT in gene-target list

· 2 trials · source: ClinicalTrials.gov
NCT05897424 NCT05856331

Prolastin-CNOT in gene-target list

· 2 trials · source: ClinicalTrials.gov
NCT02282527 NCT02947087

rAAV1-CB-hAATNOT in gene-target list

· 2 trials · source: ClinicalTrials.gov
NCT01054339 NCT00430768

Alpha-1 15%NOT in gene-target list

· 2 trials · source: ClinicalTrials.gov
NCT07555483 NCT04722887

WVE-006NOT in gene-target list

· 2 trials · source: ClinicalTrials.gov
NCT06186492 NCT06405633

Aerosolized, Recombinant Alpha 1-AntitrypsinNOT in gene-target list

· 2 trials · source: ClinicalTrials.gov
NCT00157092 NCT00161707

History and physicalNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT01810458

MidazolamNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT01810458

FentanylNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT01810458

LidocaineNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT01810458

AcetaminophenNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT01810458

LorazepamNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT01810458

Oxycodone/AcetaminophenNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT01810458

OndansetronNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT01810458

Dose of 60 mg/kg Fraction IV-1 Alpha1-Proteinase InhibitorNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT00242385

Dose of 60 mg/kg alpha1-proteinase inhibitorNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT00242385

BEAM-302NOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT06389877

YOLT-202NOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT07193615

ADVM-043NOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT02168686

Alpha 1-Antitrypsin (AAT, Aralast NP)NOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT01319331

Group ANOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT03383939

Group BNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT03383939

INBRX-101/rhAAT-FcNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT03815396

Kamada-AAT for Inhalation, 80mgNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT02001688

Kamada-AAT for Inhalation, 160mgNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT02001688

AIR-001 SAD dose level 1NOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT07431112

AIR-001 SAD dose level 2NOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT07431112

AIR-001 SAD dose level 3NOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT07431112

AIR-001 SAD dose level 4NOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT07431112

AIR-001 MD dose level 1NOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT07431112

AIR-001 MD dose level 2NOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT07431112

AIR-001 MD dose level 3NOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT07431112

AIR-001 MD dose level 4NOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT07431112

AIR-001 MD dose level 5NOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT07431112

AIR-001 MD dose level 6NOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT07431112

Liquid Alpha₁-PINOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT02282527

Alpha-1 Antitrypsin (human)NOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT01669421

Alpha-1 Antitrypsin GenotypeNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT00500123

BMN 349NOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT06738017

20-valent pneumococcal conjugate vaccineNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT07135427

History and physical exam.NOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT01851642

Albuterol inhaler.NOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT01851642

PatientsNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT03470857

GLASSIANOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT02525861

Prolastin-C, 60 mg/kgNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT01213043

Prolastin-C, 120 mg/kgNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT01213043

Genetic SequencingNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT02810327

ARO-AAT InjectionNOT in gene-target list

· 1 trial · source: ClinicalTrials.gov
NCT03362242

Generated by the Open Source Medicine Foundation Biomarker Pipeline — 2026-10-08. Data sources: DGIdb, Open Targets, ChEMBL, PubMed, ClinicalTrials.gov. Not medical advice.