guanylate cyclase Inhibitors
7 drugsAbout guanylate cyclase
Guanylate cyclase (GC) catalyzes cyclic GMP (cGMP) production, a second messenger involved in various physiological processes. It plays a significant role in vasodilation, platelet aggregation, and other cellular functions.
Human genetic studies provide strong validation for targeting guanylate cyclase, with variants in GUCY1A1 linked to coronary artery disease (score 0.85) and Moyamoya disease (score 0.83). Gain-of-function variants are protective against coronary artery disease, suggesting activation may be beneficial.
Guanylate cyclase is targeted by 7 FDA-approved small molecule drugs, including NITROGLYCERIN, ADEMPAS and GENOSYL. These drugs are primarily used in cardiovascular indications, with some applications in other therapeutic areas.
guanylate cyclase Genetic Evidence Strong
Strong genetic evidence supports guanylate cyclase as a drug target, with a max genetic score of 0.85.
The strong genetic support suggests a higher probability of clinical success for guanylate cyclase-targeting drugs.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 50% directional consistency across 2 traits
- • Strong signal in cardiovascular disease, gastrointestinal disease, nervous system disease pathways
Cross-Disease Effects
Trade-off: ModerateDirection of Effect
50% alignedEvidence Across Diseases
20 totalGWAS and other genetic studies link GUCY1A1 to 26 diseases.
Activating this target may be therapeutic
Loss-of-function causes disease; activation may help
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for GUCY1A1 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 guanylate cyclase Drugs
Seven companies have approved drugs targeting guanylate cyclase, including RUBICON RESEARCH and Bayer.
The relatively low number of companies suggests moderate barriers to entry in this market.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| NITROMIST | EVUS | 2006 | 2 |
| NITROLINGUAL PUMPSPRAY | POHL BOSKAMP | 1985 | 2 |
| GENOSYL | VERO BIOTECH INC | 2019 | 2 |
| RECTIV | AbbVie | 2011 | 1 |
guanylate cyclase Drug Modality Landscape
Modalities
Routes of Administration
guanylate cyclase is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like biologics could offer a competitive advantage in this space.
guanylate cyclase Clinical Trials 184 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on guanylate cyclase. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 42 | 32 | 6 | 4 | 84% |
| Phase 2 | 83 | 46 | 31 | 6 | 60% |
| Phase 3 | 31 | 18 | 7 | 6 | 72% |
| Phase 4 | 28 | 16 | 5 | 6 | 76% |
Top Sponsors
By Modality
Top Conditions
guanylate cyclase Drug Approval Timeline (1981 - 2019)
The first drug was approved in 1981, and the most recent in 2019, spanning 39 years.
The approval timeline indicates a mature market, but opportunities may exist for novel therapies.
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Deep insights for drug target analysis
Competitive Landscape
- • 7 companies competing
- • Market share by company
Full Drug Portfolio
- • All 7 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 7-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 103 (20 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 guanylate cyclase. A trial counts if an approved drug acting on guanylate cyclase 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.