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Compound Detail

CHEMBL503

LOVASTATIN
💊 Approved Drug
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💊 Approved Drug
CC[C@H](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

Basic Information

ChEMBL ID CHEMBL503
Name LOVASTATIN
Phase Approved
Structure Type MOL
InChI Key PCZOHLXUXFIOCF-BXMDZJJMSA-N
Therapeutic ✓ Yes
Active Moiety CHEMBL1201373

Known Names

6.alpha.-methylcompactin Altoprev C10AA02 L-154803 Lovastatin Lovastatin component of advicor Lovastatina Lovastatine Mevacor Mevinacor Mevinacor 10 Mevinacor 40 +7 more
32
Targets
95
Activities
4
Assay Types
14
PK Parameters
20
Publications
19
Known Names
20
Indications
1
Mechanisms

Molecular Properties

404.6
MW (Da)
4.20
ALogP
5
HBA
1
HBD
72.8
PSA (Ų)
0.67
QED
0
Ro5 Violations
6
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 1987
Availability Prescription
Chirality Single Enantiomer

Routes of Administration

Oral

Flags

Natural Product First in Class Prodrug
USAN Stem -stat-
USAN Year 1987

Extended Properties

Molecular Formula C24H36O5
MW 404.55
Aromatic Rings 0
Heavy Atoms 29
NP-Likeness 2.34

Mechanism of Action

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

Indications

Atherosclerosis Cardiovascular Diseases Coronary Artery Disease Coronary Disease Hypercholesterolemia Heart Diseases Intermittent Claudication Lipid Metabolism Disorders Myocardial Ischemia Peripheral Vascular Diseases Arthritis, Rheumatoid Breast Neoplasms Carotid Stenosis Cerebrovascular Disorders Cognitive Dysfunction Fragile X Syndrome HIV Infections Intracranial Arteriosclerosis Intracranial Arteriovenous Malformations Learning Disabilities

ATC Classification

C10AA02
lovastatin
Level 1: CARDIOVASCULAR SYSTEM
Level 2: LIPID MODIFYING AGENTS

Activity Summary

IC50 77 meas. best 8.7
Ki 16 meas. best 9.22
EC50 1 meas. best 5.74
Kd 1 meas. best 4.89

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
3-hydroxy-3-methylglutaryl-coenzyme A reductase
CHEMBL402
Ki 9.22 9.22 0.6 1
3-hydroxy-3-methylglutaryl-coenzyme A reductase
CHEMBL402
IC50 8.7 7.2454 2.0 13
3-hydroxy-3-methylglutaryl-coenzyme A reductase
CHEMBL3247
IC50 8.66 7.7223 2.2 13
HES
CHEMBL614662
IC50 7.89 7.89 13.0 1
Rattus norvegicus
CHEMBL376
IC50 7.6 7.6 25.0 1
3-hydroxy-3-methylglutaryl-coenzyme A reductase
CHEMBL2764
IC50 7.57 7.57 27.0 1
HepG2
CHEMBL395
IC50 7.54 6.5733 29.0 3
Cholinesterase
CHEMBL5763
Ki 5.96 5.63 1100.0 2
dengue virus type 2
CHEMBL613966
EC50 5.74 5.74 1820.0 1
NON-PROTEIN TARGET
CHEMBL3879801
IC50 5.66 5.085 2200.0 4
Integrin alpha-L/beta-2 (LFA-1)
CHEMBL2364172
IC50 5.62 5.62 2400.0 1
Acetylcholinesterase
CHEMBL4078
Ki 5.57 5.57 2700.0 1
Unchecked
CHEMBL612545
IC50 5.49 5.0567 3265.8 3
Intercellular adhesion molecule (ICAM-1), Integrin alpha-L/beta-2
CHEMBL2096661
IC50 5.42 5.42 3780.0 1
Unchecked
CHEMBL612545
Ki 5.21 5.21 6142.0 1
SW480
CHEMBL612544
IC50 5.15 5.15 7100.0 1
Sodium-dependent dopamine transporter
CHEMBL238
Ki 5.09 5.09 8028.0 1
Sodium-dependent noradrenaline transporter
CHEMBL222
Ki 5.06 5.06 8680.0 1
Sodium-dependent noradrenaline transporter
CHEMBL222
IC50 5.06 5.06 8753.0 1
Substance-K receptor
CHEMBL2327
Ki 5.03 5.03 9408.0 1
ATP-dependent translocase ABCB1
CHEMBL4302
IC50 5.0 4.56 10000.0 4
Sodium-dependent dopamine transporter
CHEMBL238
IC50 5.0 5.0 10104.0 1
Histone deacetylase 1
CHEMBL325
IC50 4.95 4.93 11214.0 3
A549
CHEMBL392
IC50 4.94 4.94 11400.0 1
Leishmania infantum
CHEMBL612848
IC50 4.89 4.645 12900.0 6
Integrin alpha-L
CHEMBL1803
Kd 4.89 4.89 12900.0 1
Adenosine receptor A1
CHEMBL226
Ki 4.81 4.81 15586.0 1
Histone deacetylase 6
CHEMBL1865
IC50 4.79 4.79 16283.0 3
Acyl-CoA:cholesterol acyltransferase
CHEMBL6141
IC50 4.78 4.78 16800.0 1
Bile salt export pump
CHEMBL6020
IC50 4.71 4.71 19300.0 2
Androgen receptor
CHEMBL3072
Ki 4.7 4.7 20110.0 1
Hs68
CHEMBL614578
IC50 4.63 4.63 23200.0 1
Histone deacetylase 2
CHEMBL1937
IC50 4.59 4.59 25933.0 3
Adenosine receptor A1
CHEMBL226
IC50 4.57 4.57 26720.0 1
Solute carrier organic anion transporter family member 1B1
CHEMBL1697668
IC50 4.55 4.55 28000.0 1
Substance-K receptor
CHEMBL2327
IC50 4.55 4.55 28224.0 1
Androgen receptor
CHEMBL3072
IC50 4.52 4.52 30164.0 1
MEF
CHEMBL614342
IC50 4.46 4.46 35000.0 1
HT-29
CHEMBL384
IC50 4.33 4.33 46800.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 96.28 ng.hr.mL-1 Homo sapiens
AUC 245.2 - Chlorocebus sabaeus
CL 7.2 mL.min-1.kg-1 Homo sapiens
CL 6.5 mL.min-1.kg-1 Homo sapiens
CL 7.2 mL.min-1.kg-1 Homo sapiens
CL 7.2 mL.min-1.kg-1 Homo sapiens
Cmax 25.0 nM Homo sapiens
F 20.0 % Homo sapiens
F 5.0 % Homo sapiens
Fu 0.043 - Homo sapiens
Fu 0.043 - Homo sapiens
Fu 0.22 - Homo sapiens
MRT 1.3 hr Homo sapiens
T1/2 1.4 hr 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 Ki = 0.6 nM 9.22 Inhibition of human HMGCoA reductase -
3-hydroxy-3-methylglutaryl-coenzyme A reductase IC50 = 2.0 nM 8.7 Inhibition of human HMGCoA reductase -
3-hydroxy-3-methylglutaryl-coenzyme A reductase IC50 = 2.2 nM 8.66 Inhibition of rat liver HMG-CoA reductase pre incubated for 5 mins followed by s... 30243589
3-hydroxy-3-methylglutaryl-coenzyme A reductase IC50 = 2.2 nM 8.66 Inhibition of HMG-CoA reductase (unknown origin) using [14C]-HMG-CoA as substrat... 28850227
3-hydroxy-3-methylglutaryl-coenzyme A reductase IC50 = 3.0 nM 8.52 Inhibition of rat liver microsomal HMG-CoA reductase 8246234
3-hydroxy-3-methylglutaryl-coenzyme A reductase IC50 = 7.0 nM 8.15 Tested for inhibition of rat liver microsomal HMG-CoA reductase 7932551
3-hydroxy-3-methylglutaryl-coenzyme A reductase IC50 = 8.0 nM 8.1 In vitro inhibition of HMG-CoA reductase of rat liver 2153213
3-hydroxy-3-methylglutaryl-coenzyme A reductase IC50 = 8.0 nM 8.1 In vitro inhibition of HMG-CoA reductase in solubilized rat liver. 1656041
3-hydroxy-3-methylglutaryl-coenzyme A reductase IC50 = 8.0 nM 8.1 In vitro inhibition of rat liver HMG-CoA reductase 2296036
3-hydroxy-3-methylglutaryl-coenzyme A reductase IC50 = 11.0 nM 7.96 Inhibition of microsomal rat liver HMG-CoA reductase -
HES IC50 = 13.0 nM 7.89 Concentration required to inhibit HMG-CoA reductase by 50% was determined in HES... 1527791
3-hydroxy-3-methylglutaryl-coenzyme A reductase IC50 = 20.0 nM 7.7 Tested in vitro for the inhibition of HMG-CoA reductase from partially purified ... 1597859
3-hydroxy-3-methylglutaryl-coenzyme A reductase IC50 = 20.0 nM 7.7 DRUGMATRIX: HMG-CoA Reductase enzyme inhibition (substrate: [14C]HMG-CoA) -
Rattus norvegicus IC50 = 25.0 nM 7.6 Compound was tested for its Cholesterol Synthesis Inhibition ability in rats. 1992138
3-hydroxy-3-methylglutaryl-coenzyme A reductase IC50 = 27.0 nM 7.57 In vitro inhibitory activity was measured against rat liver HMG-CoA reductase 2231596
3-hydroxy-3-methylglutaryl-coenzyme A reductase IC50 = 27.0 nM 7.57 In vitro inhibitory activity against isolated enzyme HMG-CoA reductase -
3-hydroxy-3-methylglutaryl-coenzyme A reductase IC50 = 28.0 nM 7.55 Compound was evaluated for the inhibition of HMG-CoA reductase (COR) in rats. 1992138
HepG2 IC50 = 29.0 nM 7.54 Tested for inhibition of cholesterol biosynthesis in HEP G2 cells 7932551
3-hydroxy-3-methylglutaryl-coenzyme A reductase IC50 = 29.5 nM 7.53 Reductase Activity Assay: The HMGR activity was performed using HMG-CoA reductas... -
3-hydroxy-3-methylglutaryl-coenzyme A reductase IC50 = 29.5 nM 7.53 Reductase Activity Assay: The HMGR activity was performed using HMG-CoA reductas... -

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL3885881 Rattus norvegicus 760
- 10.6019/CHEMBL4689842 HEK-293T 346
- 10.6019/CHEMBL4689842 U2OS 344
- 10.6019/CHEMBL4689842 Fibroblast 342
- 10.5281/zenodo.13943903 ADMET 87
17472962 10.1074/jbc.m610350200 SW480 22
24556504 10.1016/j.bmc.2014.01.051 MDA-MB-231 20
16472241 10.2174/1570163043334794 Hepatotoxicity 18
8340925 10.1021/jm00067a022 Cricetinae gen. sp. 18
22194678 10.1371/journal.pcbi.1002310 Hepatotoxicity 14
15646539 10.1016/s0399-8320(04)95062-2 Unchecked 11
20088515 10.1021/jm901685n Mus musculus 9
20070106 10.1021/jm901371v Homo sapiens 8
15646539 10.1016/s0399-8320(04)95062-2 NON-PROTEIN TARGET 8
21872367 10.1016/j.ejmech.2011.08.012 3-hydroxy-3-methylglutaryl-coenzyme A reductase 7
1597859 10.1021/jm00089a022 Canis familiaris 6
33479686 10.1039/d0md00073f Leishmania infantum 6
17502414 10.1128/aac.01330-06 Plasmodium falciparum 6
21550257 10.1016/j.bmc.2011.04.019 Unchecked 6
15454225 10.1016/j.bmcl.2004.08.015 Rattus norvegicus 6

Data from ChEMBL 36 via Core Engine