HMGCR 3-hydroxy-3-methylglutaryl-CoA reductase
ENSG00000113161 · protein coding · Open Targets profile
Catalyzes the conversion of (3S)-hydroxy-3-methylglutaryl-CoA (HMG-CoA) to mevalonic acid, the rate-limiting step in the synthesis of cholesterol and other isoprenoids, thus plays a critical role in cellular cholesterol homeostasis (PubMed:21357570, PubMed:2991281, PubMed:36745799, PubMed:6995544). HMGCR is the main target of statins, a class of cholesterol-lowering drugs (PubMed:11349148, PubMed:18540668, PubMed:36745799). {ECO:0000269|PubMed:11349148, ECO:0000269|PubMed:18540668, ECO:0000269|PubMed:21357570, ECO:0000269|PubMed:2991281, ECO:0000269|PubMed:36745799, ECO:0000269|PubMed:6995544}.
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 Withdrawn means the drug was pulled from the market or from development.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
- Literature, UniProt Ubiquitination, Database Ubiquitination, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.3223699927330017 (upper bound 0.43299999833106995). 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 400 registry trials, updated in the last three years, of the most advanced drugs against HMGCR (rosuvastatin calcium, lovastatin, pitavastatin, pitavastatin magnesium, pravastatin, atorvastatin calcium, pitavastatin calcium, atorvastatin, simvastatin, fluvastatin, rosuvastatin), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Bolanle A OmotosoObafemi Awolowo University /Teaching Hospital, Ile- Ife, Osun State, Nigeria · 2 of 2 trials Phase 2+
- Clifton FullerM.D. Anderson Cancer Center · 2 of 2 trials Phase 2+
- khadija glalassistant lecturer · 2 of 2 trials Phase 2+
- Linn H SteffensenUniversity Hospital Northern Norway · 2 of 2 trials Phase 2+
- Marte-Helene BjørkHaukeland University Hospital · 2 of 2 trials Phase 2+
- mohamed G. Zeinhomneurology department kafr el-sheikh university · 2 of 2 trials Phase 2+
- Olanisun O AdewoleObafemi Awolowo University / Teaching Hospital, Ile Ife, Nigeria · 2 of 2 trials Phase 2+
- Maged CostantineOhio State University · 1 of 2 trials Phase 2+
- Sophia ZoungasMonash University · 1 of 2 trials Phase 2+
- Teresa ChenBeijing Inno Medicine Co., Ltd. · 1 of 2 trials Phase 2+
- Abdullah Al Shafi MajumderProfessor, Dept. of Cardiology, Popular Medical College, Dhaka. · 1 of 1 trials Phase 2+
- Abigail SmithNorthwestern University · 1 of 1 trials Phase 2+
- Adam CohenInova Health Care Services · 1 of 1 trials Phase 2+
- Aet Elken (Saar)Heart Clinic, Tartu University Hospital · 1 of 1 trials Phase 2+
- Aflak RasheedShaikh Zayed Hospital, Lahore · 1 of 1 trials Phase 2+
Registry trials of rosuvastatin calcium, lovastatin, pitavastatin, pitavastatin magnesium, pravastatin, atorvastatin calcium, pitavastatin calcium, atorvastatin, simvastatin, fluvastatin, rosuvastatin 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; 342 of 376 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. 24 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
248 trials of drugs against HMGCR were stopped early; 24 of the 200 most recent give no reason
Terminated, withdrawn and suspended interventional trials of rosuvastatin calcium, lovastatin, pitavastatin, pitavastatin magnesium, pravastatin, atorvastatin calcium, pitavastatin calcium, atorvastatin, simvastatin, fluvastatin, rosuvastatin, 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 25 most recent of 248.
- withdrawn · 2026-10-07 · Dr. Md. Alimur Reza · Atorvastatin 10 mg and ezetimibe 10 mg, Atorvastatin 20 mg“Withdrawn by the sponsor before any participant was enrolled. Protocol-specified screening and randomization were not initiated at the study site. Not related to participant safety.”
- withdrawn · 2026-10-05 · The George Institute · Atorvastatin“Funding issues.”
- withdrawn · 2026-09-08 · Eli Lilly and Company · Simvastatin“The sponsor made a business decision to withdraw the trial.”
- terminated · 2026-08-06 · Chang Gung Memorial Hospital · Simvastatin“Slow recruitment and exhaustion of available study funding.”
- terminated · 2026-05-22 · Henan Institute of Cardiovascular Epidemiology · Rosuvastatin 20 mg“Slow patient enrollment and lack of financial support”
- withdrawn · 2026-05-12 · Bayer · Rosuvastatin“The study is no longer required.”
- terminated · 2026-05-07 · Columbia University · Atorvastatin“The study was terminated early due to recruitment limitations, particularly difficulty enrolling statin-naïve patients”
- terminated · 2026-04-27 · Seoul National University Hospital · matched by the registry's drug synonyms“The study was terminated early due to slow recruitment and the Principal Investigator's retirement.”
- suspended · 2026-04-23 · Sclnow Biotechnology Co., Ltd. · Aspirin Enteric-coated Tablets & Atorvastatin Calcium“Others”
- terminated · 2026-04-13 · Dr. B. Catharine. Craven · Rosuvastatin Calcium“COVID-19 Pandemic”
- terminated · 2025-12-23 · The George Washington University Biostatistics Center · Pravastatin“participants are no longer being examined or receiving intervention”
- terminated · 2025-11-25 · Universitaire Ziekenhuizen KU Leuven · Rosuvastatin 10mg“Due to the university's termination of its contract with the online questionnaire platform, we decided to discontinue the study before reaching the anticipated sample size.”
- withdrawn · 2025-04-22 · ViiV Healthcare · matched by the registry's drug synonyms“Sponsor decision”
- withdrawn · 2025-04-01 · Turning Point Therapeutics, Inc. · Rosuvastatin Calcium“Insufficient enrollment”
- terminated · 2025-03-20 · Enrique de-Madaria · Simvastatin 40mg“Slow recruitment”
- withdrawn · 2025-03-17 · University of Louisville · matched by the registry's drug synonyms“study withdrawn, no participants enrolled, changes in the study design planned”
- terminated · 2025-01-30 · Penn State University · Atorvastatin“COVID halting human subjects research and preliminary data from this proposal were used to submit an NIH grant. The NIH grant was funded and 3 other protocols were launched.”
- withdrawn · 2025-01-13 · Montefiore Medical Center · Atorvastatin 80 Mg Oral Tablet, Pravastatin 40 Mg Oral Tablet“Study never submitted. Study team instead conducted a retrospective study which did not qualify for registration.”
- withdrawn · 2024-12-18 · Piedmont Healthcare · matched by the registry's drug synonyms“Lack of patient population”
- terminated · 2024-11-15 · Pfizer · Rosuvastatin“The decision to terminate clinical development of lotiglipron is based on pharmacokinetic data from Phase 1 drug-drug-interaction studies and laboratory measurements of elevated transaminases in these Phase 1 studies as well as a Phase 2 study.”
- terminated · 2024-11-08 · paresh Dandona · Simvastatin 40mg“Lack of recruitment- Fellow responsible for study graduated”
- terminated · 2024-10-09 · National Heart, Lung, and Blood Institute (NHLBI) · Rosuvastatin, Atorvastatin“Principal Investigator resigned and closed program”
- terminated · 2024-10-02 · M.D. Anderson Cancer Center · Atorvastatin“Due to slow accrual”
- terminated · 2024-09-19 · Juan D. Maya · 40 mg Atorvastatin/day for 120 days P.O., Atorvastatin 80“The recruitment rate in all centers was extremely low. The number of participants failed to reach a statistically significant minimum.”
- terminated · 2024-08-15 · Organon and Co · MK0653A, ezetimibe (+) simvastatin / Duration of Treatment: 6 Weeks, Comparator: atorvastatin / Duration of Treatment: 6 Weeks“This study was terminated early due to poor recruitment.”
Paediatric incentives and obligations for HMGCR's drugs
For rosuvastatin calcium, lovastatin, pitavastatin, pitavastatin magnesium, pravastatin, atorvastatin calcium, pitavastatin calcium, atorvastatin, simvastatin, fluvastatin, rosuvastatin: 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 · HMGCR 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 · EMA/PE/0000257220 (bempedoic acid;ezetimibe;atorvastatin, Treatment of mixed dyslipidaemia): W: decision granting a waiver in all age groups for all conditions or indications, 10 Jul 2025; EMA/PE/0000257216 (bempedoic acid;ezetimibe;atorvastatin, Treatment of elevated cholesterol): W: decision granting a waiver in all age groups for all conditions or indications, 10 Jul 2025; EMA/PE/0000230564 (ezetimibe;rosuvastatin, Treatment of cardiovascular disease): W: decision granting a waiver in all age groups for all conditions or indications, 21 Mar 2025; EMA/PE/0000228360 (ezetimibe;rosuvastatin, Treatment of hypercholesterolaemia): W: decision granting a waiver in all age groups for all conditions or indications, 28 Jan 2025; +111 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: yes · EU/3/22/2714 positive 11 Nov 2022: Treatment of familial cerebral cavernous malformations; EU/3/10/748 positive 9 Jun 2010: Treatment of Hutchinson-Gilford progeriaRule: 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 · Cholib: authorised since 26 Aug 2013; Pravafenix: authorised since 14 Apr 2011Rule: 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 rosuvastatin calcium, lovastatin, pitavastatin, pitavastatin magnesium, pravastatin, atorvastatin calcium, pitavastatin calcium, atorvastatin, simvastatin, fluvastatin, rosuvastatinRule: 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 · 158 interventional studies of rosuvastatin calcium, lovastatin, pitavastatin, pitavastatin magnesium, pravastatin, atorvastatin calcium, pitavastatin calcium, atorvastatin, simvastatin, fluvastatin, rosuvastatin include patients under 18; 15 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 16 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.