FKBP-12 Inhibitors
15 drugsAbout FKBP-12
FKBP-12 (FK506 binding protein 12) is an intracellular protein regulating cellular processes. It is a drug target with immunosuppressants modulating its activity.
Genetic evidence offers moderate support for FKBP-12 as a therapeutic target (max score 0.51). Loss-of-function variants are protective against Sjogren syndrome, suggesting inhibition may be beneficial.
FKBP-12 is targeted by 15 FDA-approved small molecule drugs, including TACROLIMUS (PROGRAF) and SIROLIMUS. These drugs are marketed by 11 companies, including Novartis and Astellas, across oncology and immunology.
FKBP-12 Genetic Evidence Moderate
Genetic evidence shows moderate support with a max score of 0.51 linking FKBP-12 to alcohol drinking.
Further research into the genetic associations could reveal novel therapeutic opportunities.
💡 Why inhibition?
- • Loss-of-function variants reduce disease risk (OR < 1)
- • 100% directional consistency across 1 traits
- • Strong signal in gastrointestinal disease, immune system disease, disorder of visual system pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
3 totalGWAS and other genetic studies link FKBP1A to 3 diseases.
🔗 Colocalization Evidence 2 strong
max H4: 1.00eQTL/pQTL signals for FKBP1A colocalize with these GWAS traits, providing causal evidence that gene expression changes drive disease risk.
Understanding these scores
Association Score (0-1): Combines all evidence types (genetic, literature, drugs, animal models). Higher = more evidence linking target to disease. This is a ranking heuristic, not a confidence score.
L2G Score: Open Targets uses a machine learning model (Locus-to-Gene) to predict which gene is causal at each GWAS locus. L2G=0.5 means ~50% probability of being the causal gene. Only associations with L2G > 0.05 are included.
Odds Ratio (OR): From gene burden studies (UK Biobank, AstraZeneca PheWAS). Measures how loss-of-function variants affect disease risk. OR<1 = protective (inhibiting target may help), OR>1 = risk (losing function causes disease).
Beta (β): Effect size for continuous traits. β<0 = protective, β>0 = risk.
Clinical Translation (~1.8x): Based on Nelson et al. 2015: drug targets with genetic evidence have ~2x higher success rates in clinical trials. We estimate: Strong support (score ≥0.7) → ~1.8x, Moderate (0.3-0.7) → ~1.3x, Weak → baseline.
Colocalization (H4): Tests whether a GWAS signal and an eQTL/pQTL signal share the same causal variant. H4 is the posterior probability that both traits are associated AND share a causal variant. H4 > 0.8 = strong evidence that gene expression/protein levels drive disease risk. This links genetic variation → gene expression → disease, supporting the target-disease connection.
Top FKBP-12 Drugs
Eleven companies have approved drugs targeting FKBP-12, with Accord Hlthcare and Astellas among the top players.
The presence of multiple companies suggests a competitive market, requiring a differentiated strategy for new entrants.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| AFINITOR DISPERZ | Novartis | 2012 | 7 |
| SIROLIMUS | Apotex | 2014 | 2 |
| PROGRAF | ASTELLAS | 1994 | 1 |
| TEMSIROLIMUS | ACCORD HLTHCARE | 2018 | 1 |
| FYARRO | AADI | 2021 | 1 |
| ASTAGRAF XL | ASTELLAS | 2013 | 1 |
| ENVARSUS XR | VELOXIS PHARMS INC | 2015 | 1 |
| ZORTRESS | Novartis | 2010 | 1 |
| ELIDEL | BAUSCH | 2001 | 1 |
| PIMECROLIMUS | GLENMARK PHARMS LTD | 2018 | 1 |
| PROTOPIC | LEO PHARMA AS | 2000 | 1 |
| TACROLIMUS | Viatris | 2009 | - |
FKBP-12 Drug Modality Landscape
Modalities
Routes of Administration
FKBP-12 is amenable to small molecule drugs, with oral options available for convenient dosing.
Given the modality concentration, exploring alternative modalities like antibodies could provide a competitive advantage.
FKBP-12 Clinical Trials 1,434 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on FKBP-12. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 449 | 275 | 81 | 90 | 77% |
| Phase 2 | 617 | 305 | 137 | 172 | 69% |
| Phase 3 | 151 | 84 | 22 | 45 | 79% |
| Phase 4 | 217 | 160 | 27 | 30 | 86% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Phase 3 Readout Calendar Pro
8 Phase 3 trials testing approved FKBP-12 drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting FKBP-12. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
FKBP-12 Drug Approval Timeline (1994 - 2021)
The first drug targeting FKBP-12 was approved in 1994 (PROGRAF), and the most recent was in 2021 (FYARRO).
The continued approvals indicate sustained interest, but market saturation warrants careful consideration.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 11 companies competing
- • Market share by company
Full Drug Portfolio
- • All 15 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 15-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 515 (108 companies)
- • Completion rates by condition
Full summary • All drugs • Genetic evidence • Trials • Timeline
How We Count Trials
- Trials: phase 1-4 interventional trials on ClinicalTrials.gov that started in 2008 or later and test an FDA-approved drug acting on FKBP-12. A trial counts if an approved drug acting on FKBP-12 is in any arm, including as a comparator, and a trial that tests two such drugs counts once. Trials that test only unapproved drugs are not counted. A trial listed as phase 1/2 counts as phase 1, and phase 2/3 as phase 2.
- Active: recruiting, not yet recruiting, enrolling by invitation, or active and no longer recruiting.
- Completion rate: of the trials that have ended, the share marked Completed rather than Terminated or Withdrawn. Completed means the trial ended as planned; it does not mean the drug worked. Suspended trials are not counted as ended.
- Stopped: terminated or withdrawn. Trials stop for many reasons, including slow enrolment and business decisions, not only safety or efficacy.
- Sponsors: the lead sponsor of each trial. Companies are the sponsors ClinicalTrials.gov classes as industry; the rest are universities, hospitals, cooperative groups, government bodies and individuals.