CYP3A4 cytochrome P450 family 3 subfamily A member 4
ENSG00000160868 · protein coding · Open Targets profile
A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta- estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta- hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C- 4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15- epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate- limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo- monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981). {ECO:0000269|PubMed:10681376, ECO:0000269|PubMed:10759686, ECO:0000269|PubMed:11093772, ECO:0000269|PubMed:11159812, ECO:0000269|PubMed:11555828, ECO:0000269|PubMed:11695850, ECO:0000269|PubMed:12865317, ECO:0000269|PubMed:14559847, ECO:0000269|PubMed:15373842, ECO:0000269|PubMed:15764715, ECO:0000269|PubMed:19965576, ECO:0000269|PubMed:20702771, ECO:0000269|PubMed:21490593, ECO:0000269|PubMed:21576599, ECO:0000269|PubMed:22773874, ECO:0000269|PubMed:2732228, ECO:0000269|PubMed:29461981, ECO:0000269|PubMed:8968357, ECO:0000269|PubMed:9435160}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Approved Drug, Structure with Ligand, High-Quality Ligand, High-Quality Pocket, Druggable Family
- Antibody
- UniProt SigP or TMHMM
- PROTAC
- UniProt Ubiquitination, Database Ubiquitination, Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.7464900016784668 (upper bound 0.9685699939727783). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 43 registry trials, updated in the last three years, of the most advanced drugs against CYP3A4 (cobicistat, tabimorelin), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Adriano LazzarinOspedale San Raffaele · 1 of 1 trials Phase 2+
- Alejandro L CuentasAsociación Civil Selva Amazónica (ACSA) · 1 of 1 trials Phase 2+
- Angela R SmithSyndax Pharmaceuticals · 1 of 1 trials Phase 2+
- Antoine ChéretHôpital Bicêtre · 1 of 1 trials Phase 2+
- DAVID ZUCMANHOPITAL de FOCH · 1 of 1 trials Phase 2+
- FAÏZA AJANACH de TOURCOING · 1 of 1 trials Phase 2+
- Georg BehrensHannover Medical School · 1 of 1 trials Phase 2+
- Gilles PIALOUXHOSPITAL TENON · 1 of 1 trials Phase 2+
- Gilles WandelerInselspital, Bern, Switzerland · 1 of 1 trials Phase 2+
- GWENAEL LE MOALPoitiers University Hospital · 1 of 1 trials Phase 2+
- JEAN - MICHEL MOLINACHU SAINT LOUIS · 1 of 1 trials Phase 2+
- JEAN - PAUL VIARDCH d'HOTEL DIEU · 1 of 1 trials Phase 2+
- Jordan E. LakeHouston AIDS Research Team CRS · 1 of 1 trials Phase 2+
- Jorge A. Gallardo-CartagenaBarranco CRS · 1 of 1 trials Phase 2+
- Julie BotteroBicetre Hospital · 1 of 1 trials Phase 2+
Registry trials of cobicistat, tabimorelin updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 29 of 39 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 4 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
15 trials of drugs against CYP3A4 were stopped early; 2 give no reason
Terminated, withdrawn and suspended interventional trials of cobicistat, tabimorelin, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 15 most recent of 15.
- terminated · 2026-04-08 · National Institute of Allergy and Infectious Diseases (NIAID) · matched by the registry's drug synonyms“Trial terminated by Sponsor.”
- withdrawn · 2025-07-30 · Juan A. Arnaiz · elvitegravir/cobicistat/emtricitabine/tenofovir“No participants enrolled”
- terminated · 2025-03-25 · German Cancer Research Center · Cobicistat Oral Tablet“lack of efficacy paired with high toxicity”
- terminated · 2024-12-03 · Gilead Sciences · Cobicistat“Sponsor's decision to change the clinical development plan of this molecule. This decision is not based on efficacy or safety concerns.”
- terminated · 2024-02-09 · IRCCS San Raffaele · matched by the registry's drug synonyms“The futility analysis on 24-week results estimated that there was only 2% probability of verifying the study hypothesis of a higher proportion pat. with no residual viremia through 48w in arm E/C/F/TAF”
- terminated · 2023-01-05 · Southampton Healthcare, Inc. · matched by the registry's drug synonyms“Unable to complete enrollment goals due to unanticipated factors of screen failures, covid pandemic, and continued staffing and enrollment difficulties”
- withdrawn · 2021-07-09 · Stanford University · Darunavir/CobicistatNo reason given
- withdrawn · 2021-01-14 · Azienda Ospedaliero-Universitaria di Parma · matched by the registry's drug synonyms“The study was not approved by the Italian Medicines Agency (AIFA).”
- terminated · 2020-11-06 · Giovanni Di Perri · emtricitabine, darunavir/cobicistat, maraviroc“Sloww accrual and COVID-19 related problems (impossible to perform LPs)”
- terminated · 2020-07-07 · Janssen Pharmaceutica N.V., Belgium · Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide FDC, Cobicistat“COVID-19 pandemic impacted the BE assessment of the trial. The clinical team decided to terminate the trial in order to start a new pivotal BE trial”
- withdrawn · 2020-03-18 · Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic · Elvitegravir, Cobicistat, TAF, FTC“Haiti gained access to dolutegravir as first-line ART, so we cancelled the study before any patient was enrolled (we didn't want SOC group to receive EFV)”
- withdrawn · 2019-04-26 · Henry M. Jackson Foundation for the Advancement of Military Medicine · matched by the registry's drug synonyms“Feeder cohort study closed.”
- terminated · 2018-01-02 · St Stephens Aids Trust · matched by the registry's drug synonyms“Insufficient enrolment and "business reasons"”
- terminated · 2017-02-02 · University Hospital, Basel, Switzerland · cobicistat“No additional patients fulfilling the inclusion criteria”
- terminated · 2012-07-26 · Ferrer Internacional S.A. · matched by the registry's drug synonymsNo reason given
Paediatric incentives and obligations for CYP3A4's drugs
For cobicistat, tabimorelin: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · CYP3A4 is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMEA-001825-PIP01-15-M05 (darunavir;cobicistat;emtricitabine;tenofovir alafenamide, Treatment of human immunodeficiency virus type-1 (HIV-1) infection): PM: decision on the application for modification of an agreed PIP, 16 Aug 2024; EMEA-001280-PIP01-12-M06 (darunavir;cobicistat, Treatment of human immunodeficiency virus (HIV-1) infection): PM: decision on the application for modification of an agreed PIP, 14 Jul 2023; EMA/PE/0000221021 (cobicistat;atazanavir (as sulfate), Treatment of human immunodeficiency virus (HIV-1) infection): PM: decision on the application for modification of an agreed PIP, 6 Dec 2024; EMEA-000969-PIP01-10-M06 (cobicistat, Treatment of human immunodeficiency virus (HIV-1) infection): PM: decision on the application for modification of an agreed PIP, 22 Aug 2022; +3 moreRule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: no · No EU orphan designation names cobicistat, tabimorelinRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: yes · Symtuza: authorised since 21 Sept 2017; Rezolsta: authorised since 19 Nov 2014; Genvoya: authorised since 19 Nov 2015; Stribild: authorised since 24 May 2013; +2 moreRule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of cobicistat, tabimorelinRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-12
- Registered studies open to children: yes · 10 interventional studies of cobicistat, tabimorelin include patients under 18; 3 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-12
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 3 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.
| Drug | Type | Highest stage | Indications | Source records |
|---|---|---|---|---|
| COBICISTAT | Small molecule | phase 4 | HIV infectious disease, HIV-1 infection, infection, hepatitis B virus infection, hepatitis C virus infection, malaria, acute myeloid leukemia, acute leukemia, +4 more | Open Targets · ChEMBL |
| TABIMORELIN | Small molecule | phase 2 | – | Open Targets · ChEMBL |
| RITONAVIR | Small molecule | withdrawal | chronic hepatitis C virus infection, HIV infectious disease, HIV-1 infection, hepatitis C virus infection, viral infectious disease, malaria, hyperlipidemia, hepatitis B virus infection, +46 more | Open Targets · ChEMBL |