Compound Detail

CHEMBL1064

SIMVASTATIN

💊 Approved Drug

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💊 Approved Drug

CCC(C)(C)C(=O)O[C@H]1C[C@@H](C)C=C2C=C[C@H](C)[C@H](CC[C@@H]3C[C@@H](O)CC(=O)O3)[C@H]21

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL1064
Name	SIMVASTATIN
Phase	Approved
Structure Type	MOL
InChI Key	RYMZZMVNJRMUDD-HGQWONQESA-N
Therapeutic	✓ Yes
Active Moiety	CHEMBL1201391

Known Names

C10AA01 Flolipid Lacersa MK-0733 MK-733 NSC-758706 Ranzolont Simvador Simvastatin Simvastatin component of juvisync Simvastatin component of polycap Simvastatin component of simcor +6 more

Targets

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

418.6

MW (Da)

4.59

ALogP

HBA

HBD

72.8

PSA (Å²)

0.64

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
First Approval	1991
Availability	Prescription
Chirality	Single Enantiomer

Routes of Administration

Oral

Flags

Natural Product Prodrug

USAN Stem	-stat-
USAN Year	1987

Extended Properties

Molecular Formula	C25H38O5
MW	418.57
Aromatic Rings	0
Heavy Atoms	30
NP-Likeness	2.12

Mechanism of Action

Mechanism	Action Type	Target	Direct	Efficacy
HMG-CoA reductase inhibitor	INHIBITOR	3-hydroxy-3-methylglutaryl-coenzyme A reductase	✓	✓

Indications

Cardiovascular Diseases Coronary Artery Disease Coronary Disease Dyslipidemias Hypercholesterolemia Hyperlipidemias Hyperlipoproteinemia Type II Myocardial Infarction Myocardial Infarction Stroke Acute Coronary Syndrome Alzheimer Disease Aortic Valve Stenosis Asthma Atherosclerosis Cholangitis, Sclerosing Colorectal Neoplasms Depressive Disorder, Treatment-Resistant Diabetes Mellitus Diabetes Mellitus, Type 2

ATC Classification

C10AA01

simvastatin

Level 1: CARDIOVASCULAR SYSTEM

Level 2: LIPID MODIFYING AGENTS

Activity Summary

IC50 47 meas. best 9.05

Ki 6 meas. best 8.59

EC50 2 meas. best 5.74

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
3-hydroxy-3-methylglutaryl-coenzyme A reductase CHEMBL3247	IC50	9.05	8.39	0.9	3
3-hydroxy-3-methylglutaryl-coenzyme A reductase CHEMBL402	IC50	9.05	7.5825	0.9	8
Hepatocyte CHEMBL613362	IC50	8.89	8.656	1.3	5
3-hydroxy-3-methylglutaryl-coenzyme A reductase CHEMBL402	Ki	8.59	6.38	2.6	2
L6 CHEMBL614793	IC50	7.57	7.01	27.0	3
HepG2 CHEMBL395	IC50	7.4	7.4	40.0	1
Unchecked CHEMBL612545	IC50	6.82	5.495	150.0	8
Cholinesterase CHEMBL5763	Ki	6.12	5.71	750.0	2
Acetylcholinesterase CHEMBL4078	Ki	5.75	5.75	1800.0	1
dengue virus type 2 CHEMBL613966	EC50	5.74	5.74	1820.0	1
Cytochrome P450 2C8 CHEMBL3721	IC50	5.43	5.43	3700.0	1
Solute carrier organic anion transporter family member 1B1 CHEMBL1697668	IC50	5.36	5.1375	4400.0	4
Nuclear receptor subfamily 4 group A member 2 CHEMBL5002	EC50	5.29	5.29	5100.0	1
ATP-dependent translocase ABCB1 CHEMBL4302	IC50	5.05	4.644	9000.0	5
A549 CHEMBL392	IC50	4.79	4.79	16300.0	1
Bile salt export pump CHEMBL6020	IC50	4.61	4.61	24700.0	3
ATP-binding cassette sub-family C member 2 CHEMBL5748	IC50	4.6	4.6	25000.0	1
Hs68 CHEMBL614578	IC50	4.58	4.58	26400.0	1
MEF CHEMBL614342	IC50	4.43	4.43	36700.0	1
3-hydroxy-3-methylglutaryl-coenzyme A reductase CHEMBL1163121	IC50	4.02	4.02	95200.0	1

Pharmacokinetic Data

Parameter	Value	Units	Species
Absorption	-	-	Rattus norvegicus
Absorption	-	-	Canis lupus familiaris
Absorption	-	-	Homo sapiens
AUC	316.0	ng.eq.h.ml-1	Homo sapiens
AUC	636.0	ng.eq.h.ml-1	Homo sapiens
AUC	1533.0	ng.eq.h.ml-1	Homo sapiens
AUC	410.0	ng.hr.mL-1	Mus musculus
AUC	3700.0	ng.hr.mL-1	Mus musculus
AUC	500.0	ng.hr.mL-1	Mus musculus
AUC	2300.0	ng.hr.mL-1	Mus musculus
AUC	5200.0	ng.hr.mL-1	Mus musculus
AUC	4400.0	ng.hr.mL-1	Rattus norvegicus
AUC	10000.0	ng.hr.mL-1	Rattus norvegicus
AUC	14000.0	ng.hr.mL-1	Rattus norvegicus
AUC	16000.0	ng.hr.mL-1	Rattus norvegicus
AUC	1100.0	ng.hr.mL-1	Canis lupus familiaris
AUC	3300.0	ng.hr.mL-1	Canis lupus familiaris
AUC	12000.0	ng.hr.mL-1	Canis lupus familiaris
AUC	4000.0	ng.hr.mL-1	Canis lupus familiaris
AUC	5400.0	ng.hr.mL-1	Canis lupus familiaris
AUC	77.61	ng.hr.mL-1	Homo sapiens
AUC	83.89	ng.hr.mL-1	Homo sapiens
AUC	98.5	ng.hr.mL-1	Homo sapiens
AUC	101.92	ng.hr.mL-1	Homo sapiens
AUC	31.6	ng.hr.mL-1	Homo sapiens
AUC	18.5	ng.hr.mL-1	Homo sapiens
AUC	112.5	ng.hr.mL-1	Homo sapiens
AUC	62.0	ng.hr.mL-1	Homo sapiens
AUC	88.74	ng.hr.mL-1	Homo sapiens
Cmax	120.0	nM	Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
3-hydroxy-3-methylglutaryl-coenzyme A reductase	IC50	=	0.9	nM	9.05	Inhibition of HMG-CoA reductase (unknown origin) using [14C]-HMG-CoA as substrat...	28850227
3-hydroxy-3-methylglutaryl-coenzyme A reductase	IC50	=	0.9	nM	9.05	Inhibition of rat liver HMG-CoA reductase pre incubated for 5 mins followed by s...	30243589
Hepatocyte	IC50	=	1.3	nM	8.89	Inhibition of cholesterol synthesis in rat liver hepatocytes after 4 hrs	17560788
Hepatocyte	IC50	=	1.3	nM	8.89	Inhibition of cholesterol synthesis in rat hepatocyte	17574412
Hepatocyte	IC50	=	1.3	nM	8.89	Inhibition of cholesterol synthesis in rat hepatocyte	18155906
3-hydroxy-3-methylglutaryl-coenzyme A reductase	Ki	=	2.6	nM	8.59	Inhibitory constant against HMG-CoA reductase	15686898
3-hydroxy-3-methylglutaryl-coenzyme A reductase	IC50	=	3.39	nM	8.47	DRUGMATRIX: HMG-CoA Reductase enzyme inhibition (substrate: [14C]HMG-CoA)	-
Hepatocyte	IC50	=	4.0	nM	8.4	Inhibition of cholesterol synthesis in rat hepatocytes	17574411
3-hydroxy-3-methylglutaryl-coenzyme A reductase	IC50	=	4.3	nM	8.37	Inhibition of HMGR in rat hepatic microsomes assessed as conversion of [14C]HMG-...	18412317
Hepatocyte	IC50	=	6.2	nM	8.21	Inhibition of cholesterol synthesis in rat hepatocytes assessed as incorporation...	18412317
3-hydroxy-3-methylglutaryl-coenzyme A reductase	IC50	=	11.0	nM	7.96	Inhibitory concentration against 3-hydroxy-3-methylglutaryl-CoA reductase	15686906
3-hydroxy-3-methylglutaryl-coenzyme A reductase	IC50	=	11.2	nM	7.95	Inhibitory concentration against HMG-CoA reductase	15686898
3-hydroxy-3-methylglutaryl-coenzyme A reductase	IC50	=	18.0	nM	7.75	Inhibition of rat microsomal HMG-CoA reductase assessed as inhibition of cholest...	17560788
L6	IC50	=	27.0	nM	7.57	Inhibition of cholesterol synthesis in rat L6 cells assessed as incorporation of...	18412317
3-hydroxy-3-methylglutaryl-coenzyme A reductase	IC50	=	39.81	nM	7.4	Inhibition of human HMG-CoA reductase after 30 mins	25311563
HepG2	IC50	=	40.0	nM	7.4	In vitro inhibitory activity was evaluated on cholesterol biosynthesis in HepG2 ...	14741258
3-hydroxy-3-methylglutaryl-coenzyme A reductase	IC50	=	49.0	nM	7.31	Inhibition of HMGCoA reductase	17574411
3-hydroxy-3-methylglutaryl-coenzyme A reductase	IC50	=	49.0	nM	7.31	Inhibition of HMG-CoA reductase	17574412
Unchecked	IC50	=	150.0	nM	6.82	Inhibition of cholesterol synthesis in rat myocyte	17574412
L6	IC50	=	150.0	nM	6.82	Inhibition of cholesterol synthesis in rat L6 myocyte	18155906

Literature References

PubMed	DOI	Target Context	# Activities
-	10.6019/CHEMBL3885861	Rattus norvegicus	1483
-	10.6019/CHEMBL3885881	Rattus norvegicus	613
-	10.1101/2024.03.28.586928	ADMET	100
16472241	10.2174/1570163043334794	Hepatotoxicity	18
15206993	10.1111/j.1365-2125.2004.02095.x	Homo sapiens	16
22194678	10.1371/journal.pcbi.1002310	Hepatotoxicity	14
15646539	10.1016/s0399-8320(04)95062-2	Unchecked	11
15646539	10.1016/s0399-8320(04)95062-2	NON-PROTEIN TARGET	8
25740159	10.1016/j.bmcl.2015.02.013	No relevant target	8
38112492	10.1021/acs.jmedchem.3c01634	Mus musculus	6
37468498	10.1038/s41467-023-40064-9	Alpha-1A adrenergic receptor	6
38739840	10.1021/acs.jmedchem.3c01267	Syrian golden hamster	6
17502414	10.1128/aac.01330-06	Plasmodium falciparum	6
36786607	10.1021/acs.jmedchem.2c01643	Mus musculus	5
25311563	10.1016/j.bmc.2014.09.022	Mus musculus	4
18268089	10.1128/aac.01428-07	Plasmodium berghei	4
18412317	10.1021/jm800001n	Cavia porcellus	4
37468498	10.1038/s41467-023-40064-9	5-hydroxytryptamine receptor 1A	4
16107159	10.1021/jm050373g	Canis familiaris	4
37468498	10.1038/s41467-023-40064-9	Alpha-2A adrenergic receptor	4

Data from ChEMBL 36 via Core Engine