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Simvastatin

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Also known as C10AA01FlolipidLacersaMK-0733MK-733NSC-758706RanzolontSimvadorSimvastatin component of juvisyncSimvastatin component of polycapSimvastatin component of simcorSimvastatin component of vytorinSimvastatinaSimvastatineSynvinolinZocorZocor heart-proSID50086525SID496592

Summary

Simvastatin (CHEMBL1064) is an approved small-molecule EC 3.4.24.83 (anthrax lethal factor endopeptidase) inhibitor (ATC C10AA01) targeting HMGCR; indicated across 108 conditions including cardiovascular disorder and familial hypercholesterolemia.

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: C10AA01
  • Targets: 1 (HMGCR)
  • Indications: 108 conditions
  • Clinical trials: 450
  • Chemistry: 418.6 Da · C25H38O5

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL1064
NameSimvastatin
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID54454
ChEBICHEBI:9150
ATCC10AA01
Molecular formulaC25H38O5
Molecular weight418.6
InChIKeyRYMZZMVNJRMUDD-HGQWONQESA-N

SMILES: CCC(C)(C)C(=O)O[C@H]1C[C@H](C=C2[C@H]1[C@H]([C@H](C=C2)C)CC[C@@H]3C[C@H](CC(=O)O3)O)C

IUPAC name: [(1S,3R,7S,8S,8aR)-8-[2-[(2R,4R)-4-hydroxy-6-oxooxan-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl] 2,2-dimethylbutanoate

ChEBI definition: A member of the class of hexahydronaphthalenes that is lovastatin in which the 2-methylbutyrate ester moiety has been replaced by a 2,2-dimethylbutyrate ester group. It is used as a cholesterol-lowering and anti-cardiovascular disease drug.

Pharmacological roles (ChEBI): EC 3.4.24.83 (anthrax lethal factor endopeptidase) inhibitor, prodrug, EC 1.1.1.34/EC 1.1.1.88 (hydroxymethylglutaryl-CoA reductase) inhibitor, ferroptosis inducer, geroprotector.

Also known as: C10AA01, Flolipid, Lacersa, MK-0733, MK-733, NSC-758706, Ranzolont, Simvador, Simvastatin, Simvastatin component of juvisync, Simvastatin component of polycap, Simvastatin component of simcor

Patent coverage: 37,438 distinct patent families (123,163 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

GeneTargetActionpAffinityCancer dependencyUniProt
HMGCRhydroxymethylglutaryl-CoA reductaseCompetitive7.9284.4%P04035

Broader ChEMBL bioactivity targets: 39 (assay-derived). Sample: 3-hydroxy-3-methylglutaryl-coenzyme A reductase, Ferritin light chain, Solute carrier organic anion transporter family member 1B1, 5-hydroxytryptamine receptor 2B, Alpha-2C adrenergic receptor, Alpha-2B adrenergic receptor, Beta-lactamase, Glucocorticoid receptor, Bile acid receptor, D(1A) dopamine receptor.

Bioactivity

ChEMBL activities: 38 potent at pChembl ≥ 5 of 71 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
HMGCR9.05IC500.9nMCHEMBL_ACT_18168811
P516399.05IC500.9nMCHEMBL_ACT_25041352
P516399.05IC500.9nMCHEMBL_ACT_29284799
HMGCR8.59Ki2.6nMCHEMBL_ACT_1436563
HMGCR8.47IC503.39nMCHEMBL_ACT_7822360
P516398.37IC504.3nMCHEMBL_ACT_2218034
HMGCR7.96IC5011nMCHEMBL_ACT_1439881
HMGCR7.95IC5011.2nMCHEMBL_ACT_1436564
P516397.75IC5018nMCHEMBL_ACT_1974261
HMGCR7.4IC5039.81nMCHEMBL_ACT_15088046
HMGCR7.31IC5049nMCHEMBL_ACT_1907613
HMGCR7.31IC5049nMCHEMBL_ACT_2036414
NR1I36.24AC50570nMCHEMBL_ACT_25164334
NR1H46.24AC50570nMCHEMBL_ACT_25234612
P819086.12Ki750nMCHEMBL_ACT_12481282
O422755.75Ki1800nMCHEMBL_ACT_12481279
DRD15.75AC501800nMCHEMBL_ACT_25180995
NR1I25.66AC502196nMCHEMBL_ACT_25188525
HTR2A5.64AC502300nMCHEMBL_ACT_25225616
Q639215.55AC502800nMCHEMBL_ACT_25173867
CYP2C85.43IC503700nMCHEMBL_ACT_15447378
NR1I25.42AC503800nMCHEMBL_ACT_25224005
HTR2B5.42AC503800nMCHEMBL_ACT_25227986
SLCO1B15.36IC504400nMCHEMBL_ACT_15448313
ADRB35.33AC504700nMCHEMBL_ACT_25153421
P819085.3Ki5012nMCHEMBL_ACT_12481296
NR4A25.29EC505100nMCHEMBL_ACT_24824515
TBXA2R5.27AC505373nMCHEMBL_ACT_25198311
SLCO1B15.22IC506000nMCHEMBL_ACT_15448321
SLC6A35.22AC506067nMCHEMBL_ACT_25125426

Target pathways

Aggregated over 1 target gene(s): HMGCR.

Top Reactome pathways

5 total, by targets touching each:

PathwayTargetsGenes
Cholesterol biosynthesis1HMGCR
PPARA activates gene expression1HMGCR
Activation of gene expression by SREBF (SREBP)1HMGCR
EGR2 and SOX10-mediated initiation of Schwann cell myelination1HMGCR
Lanosterol biosynthesis1HMGCR

Dominant GO biological processes

GO termTargets
cholesterol biosynthetic process1
isoprenoid biosynthetic process1
visual learning1
coenzyme A metabolic process1
sterol biosynthetic process1
negative regulation of protein catabolic process1
negative regulation of protein secretion1
long-term synaptic potentiation1
regulation of ERK1 and ERK2 cascade1
negative regulation of amyloid-beta clearance1
lipid metabolic process1
steroid biosynthetic process1
steroid metabolic process1
cholesterol metabolic process1

Indications & clinical

Indications

108 indications (9 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

IndicationTrial phaseMONDOEFO
cardiovascular disorder4MONDO:0004995EFO:0000319
familial hypercholesterolemia4MONDO:0005439EFO:0004911
myocardial infarction4MONDO:0005068EFO:0000612
stroke disorder4MONDO:0005098EFO:0000712
coronary artery disorder4MONDO:0005010EFO:0001645
acute myocardial infarction4MONDO:0004781EFO:0008583
hyperlipidemia4MONDO:0021187MONDO:0021187
chronic obstructive pulmonary disease3MONDO:0005002EFO:0000341
hypertriglyceridemia3MONDO:0005347EFO:0004211
pneumonia3MONDO:0005249EFO:0003106
relapsing-remitting multiple sclerosis3MONDO:0005314EFO:0003929
subarachnoid hemorrhage3MONDO:0005099EFO:0000713
chronic kidney disease3MONDO:0005300EFO:0003884
polycystic ovary syndrome3MONDO:0008487EFO:0000660
atherosclerosis3MONDO:0005311EFO:0003914
hypertensive disorder3MONDO:0005044EFO:0000537
diabetic retinopathy3MONDO:0005266EFO:0003770
cirrhosis of liver3MONDO:0005155EFO:0001422
acute coronary syndrome3MONDO:0005542EFO:0005672
myocardial ischemia3MONDO:0024644EFO:1001375
diabetic kidney disease3MONDO:0005016EFO:0000401
sclerosing cholangitis3MONDO:0018646EFO:0004268
secondary progressive multiple sclerosis3MONDO:0000450EFO:0008522
portal hypertension3MONDO:0005080EFO:0000666
gastric neoplasm3MONDO:0021085MONDO:0001056
intestinal cancer3MONDO:0005814MONDO:0021118
diabetes mellitus3MONDO:0005015EFO:0000400
optic neuritis3MONDO:0005885EFO:0007405
severe acute respiratory syndrome3MONDO:0005091MONDO:0100096
influenza3MONDO:0005812EFO:0007328
essential hypertension3MONDO:0001134MONDO:0001134
Alzheimer disease3MONDO:0004975MONDO:0004975
asthma3MONDO:0004979MONDO:0004979
type 2 diabetes mellitus3MONDO:0005148MONDO:0005148
multiple sclerosis3MONDO:0005301MONDO:0005301
Noonan syndrome3MONDO:0018997MONDO:0018997
aortic valve stenosis3MONDO:0042981HP:0001650
colorectal neoplasm3MONDO:0005335MONDO:0005575
atrial fibrillation2MONDO:0004981EFO:0000275
breast carcinoma2MONDO:0004989EFO:0000305
intracerebral hemorrhage2MONDO:0013792EFO:0005669
non-small cell lung carcinoma2MONDO:0005233EFO:0003060
peripheral arterial disease2MONDO:0005386EFO:0004265
toxic shock syndrome2MONDO:0001881EFO:0006834
pulmonary arterial hypertension2MONDO:0015924EFO:0001361
vitiligo2MONDO:0008661EFO:0004208
sinusitis2MONDO:0005961EFO:0007486
periodontitis2MONDO:0005076EFO:0000649
rectal cancer2MONDO:0006519EFO:1000657
uveitis2MONDO:0020283EFO:1001231
small cell lung carcinoma2MONDO:0008433EFO:0000702
uterine corpus leiomyoma2MONDO:0007886EFO:0000731
plasma cell myeloma2MONDO:0009693EFO:0001378
prostate carcinoma2MONDO:0005159EFO:0001663
exocrine pancreatic carcinoma2MONDO:0005192EFO:0002618
intermittent vascular claudication2MONDO:0005295EFO:0003876
prediabetes syndrome2MONDO:0006920EFO:1001121
mucositis2MONDO:0020579EFO:1001898
dilated cardiomyopathy2MONDO:0005021EFO:0000407
Waldenstrom macroglobulinemia2MONDO:0100280EFO:0009441
carotid artery disorder2MONDO:0005269EFO:0009783
acute pancreatitis2MONDO:0006515EFO:1000652
pulmonary hypertension2MONDO:0005149MONDO:0005149
breast neoplasm2MONDO:0021100MONDO:0007254
lung neoplasm2MONDO:0021117MONDO:0008903
type 1 diabetes mellitus2MONDO:0005147MONDO:0005147
Parkinson disease2MONDO:0005180MONDO:0005180
migraine disorder2MONDO:0005277MONDO:0005277
Smith-Lemli-Opitz syndrome2MONDO:0010035MONDO:0010035
sickle cell disease2MONDO:0011382MONDO:0011382
hepatocellular carcinoma2MONDO:0007256EFO:0000182
malignant pancreatic neoplasm2MONDO:0009831EFO:1000359
bipolar disorder2MONDO:0004985MONDO:0004985
hepatitis B virus infection1MONDO:0005344EFO:0004197
HIV infectious disease1MONDO:0005109EFO:0000764
B-cell chronic lymphocytic leukemia1MONDO:0004948EFO:0000095
alopecia areata1MONDO:0005340EFO:0004192
epilepsy1MONDO:0005027EFO:0000474
rheumatoid arthritis1MONDO:0008383EFO:0000685
vascular disorder1MONDO:0005385EFO:0004264
sleep disorder1MONDO:0100081EFO:0008568
cystic fibrosis1MONDO:0009061MONDO:0009061
choroideremia1MONDO:0010557MONDO:0010557
systemic lupus erythematosus1MONDO:0007915MONDO:0007915
obesity disorder1MONDO:0011122EFO:0001073
dental caries1MONDO:0005276EFO:0003819
heart failure0MONDO:0005252EFO:0003144
lymphoma0MONDO:0005062EFO:0000574
ovarian cancer0MONDO:0008170MONDO:0008170
chronic pancreatitis0MONDO:0005003EFO:0000342
exposure, dental pulp0MONDO:0020812EFO:1001782
neoplasm0MONDO:0005070MONDO:0004992
hemangioma0MONDO:0006500EFO:1000635

15 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 450.

Phase distribution

PhaseTrials
PHASE398
PHASE497
PHASE178
PHASE274
Not specified64
PHASE2/PHASE314
EARLY_PHASE113
PHASE1/PHASE212

Top trials by phase / activity

NCTPhaseStatusTitle
NCT05059626PHASE4RECRUITINGEndometriosis and Microvascular Dysfunction; Simvastatin and Duavee
NCT06399783PHASE4NOT_YET_RECRUITINGTopical Simvastatin Versus Topical Steroid in Treatment of Alopecia Areata
NCT00079638PHASE4COMPLETEDComparative Efficacy Evaluation of Lipids When Treated With Niaspan & Statin or Other Lipid-Modifying Therapies-COMPELL
NCT00125593PHASE4COMPLETEDStudy of Heart and Renal Protection
NCT00141141PHASE4COMPLETEDEfficacy And Safety Study Of Atorvastatin Versus Simvastatin In Type 2 Diabetic Subjects With Hypercholesterolemia
NCT00146068PHASE4COMPLETEDEARLY IFNB-1a and Simvastatin Combination Therapy in Clinically Isolated Syndrome Suggestive of Multiple Sclerosis
NCT00159835PHASE4COMPLETEDAtorvastatin Versus Simvastatin In The Prevention Of Coronary Heart Disease (CHD) In Patients With Known CHD
NCT00166530PHASE4COMPLETEDEASEGO Study: Doubling of Atorvastatin/Simvastatin or INEGY in Patients With Hypercholesterolemia and Coronary Artery Disease(CAD)(0653A-089)
NCT00185107PHASE4COMPLETEDEffect of Combination Therapy With Two Drugs (Colesevelam and Ezetimibe) in Patients With High Cholesterol
NCT00189085PHASE4COMPLETEDEffects of Ezetimibe on Postprandial Hyperlipidemia and Endothelial Function
NCT00259441PHASE4COMPLETEDPROMISS: Simvastatin Prevents the Contrast Induced Acute Renal Failure in Patients With Renal Insufficiency Undergoing Coronary Angiography
NCT00291863PHASE4UNKNOWNSimvastatin Effect on End Stage Renal Failure Patients Treated by Peritoneal Dialysis
NCT00303277PHASE4COMPLETEDDo HMG CoA Reductase Inhibitors Affect Abeta Levels?
NCT00306826PHASE4WITHDRAWNPioglitazone in Impaired Glucose Tolerance
NCT00317993PHASE4COMPLETEDLDL Receptor Under Ezetimibe and Simvastatin
NCT00330980PHASE4COMPLETEDEffects of Statin Medications on Mental Processes, Behavior, and Serotonin Levels
NCT00404599PHASE4UNKNOWNOxidative Stress Lowering Effect of Simvastatin and Atorvastatin.
NCT00423579PHASE4COMPLETEDThe Effects of Ezetimibe/Simvastatin 10/20 mg Versus Simvastatin 40 mg in High Cholesterol and Coronary Heart Disease Study (P04039AM2)(COMPLETED)
NCT00450840PHASE4UNKNOWNSimvastatin in Patients With Septic Shock
NCT00451828PHASE4COMPLETEDCholesterol and Pharmacogenetic Study
NCT00466401PHASE4COMPLETEDEffect of Ezetimibe on Platelet Aggregation and LDL Tendency to Peroxidation
NCT00481351PHASE4COMPLETEDEffects of Statin and Ezetimibe Association on Kinetics of Artificial Chilomicrons
NCT00492765PHASE4COMPLETEDSimvastatin as an Add-on Treatment to Interferon-beta-1a for the Treatment of Relapsing-Remitting Multiple Sclerosis
NCT00506961PHASE4COMPLETEDEvaluate the Efficacy and Safety of Rosuvastatin Versus Simvastatin in Type 2 Diabetic Patients With Dyslipidemia
NCT00522158PHASE4COMPLETEDEffects of Achieving Very Low LDL-Cholesterol After Treatment With Statins on Steroidogenesis and Cognition
NCT00535925PHASE4COMPLETEDNephropathy In Type 2 Diabetes and Cardio-renal Events
NCT00560170PHASE4COMPLETEDVascular Effects of Ezetimibe/Simvastatin and Simvastatin on Atherosclerosis
NCT00650663PHASE4COMPLETEDEzetimibe Plus Simvastatin Versus Simvastatin Alone in African-American Subjects With Primary Hypercholesterolemia (P03377)
NCT00652444PHASE4COMPLETEDEffect Of Ezetimibe Coadministration With Simvastatin In A Middle Eastern Population: A Prospective, Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial (0653-151)
NCT00652717PHASE4COMPLETEDStudy To Assess The Efficacy Of A Cholesterol Lowering Drug On Top Of Statins In Patients After Myocardial Infarction (MI)(0653A-150)
NCT00653835PHASE4COMPLETEDEzetimibe Plus Simvastatin Versus Simvastatin in Untreated Subjects With High Cholesterol (P03435)
NCT00656292PHASE4COMPLETEDAssessing the Role of Statin Therapy and Perioperative Inflammatory Response in Patients Undergoing Major Orthopedic Surgery
NCT00669435PHASE4UNKNOWNLosartan and Simvastatin in Hypertensive Obeses With Liver Steatosis
NCT00672464PHASE4WITHDRAWNCardio Risk of Acute Schizophrenia Olanzapine Duke
NCT00678743PHASE4COMPLETEDAn Open-label Extension to Assess the Continued Efficacy of Omacor Plus Simvastatin
NCT00680641PHASE4UNKNOWNSimvastatin in Chronic Obstructive Pulmonary Disease (COPD)
NCT00699023PHASE4COMPLETEDEzetimibe and Statins on Postprandial Lipemia in Type 2 Diabetes
NCT00704548PHASE4UNKNOWNAntihypertensive Effect of Simvastatin in Hypertensive Patients
NCT00712049PHASE4UNKNOWNEffects of Nicotinic Acid Plus Simvastatin Versus Simvastatin Alone on Carotid and Femoral Intima-Media Thickness in Patients With Peripheral Artery Disease (NASCIT)
NCT00736463PHASE4UNKNOWNCrossover of Higher Dose Statins in Patients With Low High-density Lipoproteins Cholesterol (HDLc)

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

PharmGKB dosing guidelines (5) — CPIC / DPWG genotype-guided dosing for this drug (drug × pharmacogene):

GuidelineSourceGene(s)DosingRecommendation
Annotation of CPIC Guideline for simvastatin and SLCO1B1CPICSLCO1B1yesyes
Annotation of DPWG Guideline for simvastatin and SLCO1B1DPWGSLCO1B1yesyes
Annotation of RNPGx Guideline for hmg coa reductase inhibitors, simvasRNPGxSLCO1B1yesyes
Annotation of CPIC Guideline for atorvastatin, fluvastatin, lovastatinCPICABCG2
Annotation of CPIC Guideline for atorvastatin, fluvastatin, lovastatinCPICCYP3A4;CYP3A5;HMGCR

PharmGKB also curates 55 clinical and 213 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

13 molecules share ≥1 primary target. Top 13 by shared-target count:

MoleculeSourceStatusShared targets
ATORVASTATINChEMBL + PubChemPhase 4 (approved)HMGCR
LOVASTATINChEMBL + PubChemPhase 4 (approved)HMGCR
PITAVASTATINChEMBL + PubChemPhase 4 (approved)HMGCR
PRAVASTATINChEMBL + PubChemPhase 4 (approved)HMGCR
ROSUVASTATINChEMBL + PubChemPhase 4 (approved)HMGCR
CERIVASTATINChEMBLPhase 4 (approved)HMGCR
CISAPRIDEChEMBLPhase 4 (approved)HMGCR
FLUVASTATINChEMBLPhase 4 (approved)HMGCR
TANNIC ACIDChEMBLPhase 4 (approved)HMGCR
GLENVASTATINChEMBLPhase 2HMGCR
MEGLUTOLChEMBLPhase 2HMGCR
MEVASTATINChEMBLPhase 2HMGCR
VorinostatPubChemApprovedHMGCR

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 30

This page pulls from 30 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmeshmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot