Carbonic Anhydrase II Inhibitors
8 drugsAbout Carbonic Anhydrase II
Carbonic Anhydrase II (CA-II) is a zinc metalloenzyme that catalyzes the interconversion of carbon dioxide and water to bicarbonate and protons, crucial for various physiological processes.
CA-II is a therapeutic target with strong genetic support (max score 0.87) linking loss-of-function variants to osteopetrosis and renal tubular acidosis. Activation of CA-II is likely beneficial based on genetic evidence.
Eight FDA-approved small molecule drugs target CA-II, including BRINZOLAMIDE and TIMOLOL MALEATE, primarily for ophthalmological and cardiovascular applications.
Carbonic Anhydrase II Genetic Evidence Strong
CA2 has strong genetic support with a max score of 0.87 linking it to osteopetrosis and renal tubular acidosis.
Strong genetic support suggests that clinical trials targeting CA2 in genetically predisposed individuals may have a higher success rate.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 100% directional consistency across 3 traits
- • Strong signal in urinary system disease, genetic, familial or congenital disease, musculoskeletal or connective tissue disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
5 totalGWAS and other genetic studies link CA2 to 5 diseases.
Loss-of-function causes disease; activation may help
Loss-of-function causes disease; activation may help
🔗 Colocalization Evidence 19 strong
max H4: 0.99eQTL/pQTL signals for CA2 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 Carbonic Anhydrase II Drugs
Five companies have approved drugs targeting CA-II, with Novartis and Bausch & Lomb among the top players.
The presence of established companies suggests a moderately competitive market, requiring differentiated strategies for new entrants.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| DORZOLAMIDE HYDROCHLORIDE AND TIMOLOL MALEATE | Teva | 2008 | 2 |
| COSOPT PF | THEA PHARMA | 2012 | 2 |
| BRINZOLAMIDE | WATSON LABS | 2020 | 2 |
| DORZOLAMIDE HYDROCHLORIDE | Novartis | 2008 | 2 |
| TIMOLOL | EPIC PHARMA LLC | 2016 | 2 |
Carbonic Anhydrase II Drug Modality Landscape
Modalities
Routes of Administration
Carbonic Anhydrase II is druggable by small molecules, though no oral formulations are currently approved.
The absence of other modalities like antibodies or biologics represents a whitespace opportunity for novel therapeutic development.
Carbonic Anhydrase II Clinical Trials 187 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on Carbonic Anhydrase II. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 19 | 13 | 3 | 3 | 81% |
| Phase 2 | 40 | 32 | 3 | 5 | 91% |
| Phase 3 | 57 | 44 | 8 | 5 | 85% |
| Phase 4 | 71 | 57 | 12 | 2 | 83% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Carbonic Anhydrase II Drug Approval Timeline (1998 - 2020)
The first drug targeting CA-II was approved in 1989 (TIMOLOL MALEATE), with the most recent approval in 2020 (BRINZOLAMIDE), spanning 32 years.
The continued approvals indicate sustained interest in CA-II as a target, but the slowing pace suggests potential market saturation.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 5 companies competing
- • Market share by company
Full Drug Portfolio
- • All 8 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 8-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 80 (35 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 Carbonic Anhydrase II. A trial counts if an approved drug acting on Carbonic Anhydrase II 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.