hydroxymethylglutaryl-CoA reductase | Lanosterol biosynthesis pathway | IUPHAR/BPS Guide to PHARMACOLOGY

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hydroxymethylglutaryl-CoA reductase

Target not currently curated in GtoImmuPdb

Target id: 639

Nomenclature: hydroxymethylglutaryl-CoA reductase

Family: Lanosterol biosynthesis pathway

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 888 5q13.3-q14 HMGCR 3-hydroxy-3-methylglutaryl-CoA reductase 32
Mouse - 497 13 D1; 13 49.0 cM Hmgcr 3-hydroxy-3-methylglutaryl-Coenzyme A reductase
Rat - 887 2q12 Hmgcr 3-hydroxy-3-methylglutaryl-CoA reductase
Previous and Unofficial Names
beta-hydroxy-beta-methylglutaryl coenzyme A reductase | HMG CoA reductase | HMG1 | HMG2 | HMG2.2 | HMG3.3 | HMG-CoAR | HMGCR | HMGR | HMGR1 | HMGR2 | mevalonate:NADP+ oxidoreductase (acetylating CoA) | NADPH-hydroxymethylglutaryl-CoA reductase | 3H3M
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Complex of the catalytic portion of human HMG-COA reductase with atorvastatin
PDB Id:  1HWK
Ligand:  atorvastatin
Resolution:  2.22Å
Species:  Human
References:  27
Enzyme Reaction
EC Number: 1.1.1.34 (S)-3-hydroxy-3-methylglutaryl-CoA + NADPH -> (R)-mevalonate + coenzyme A + NADP+
Description Reaction Reference
Reaction mechanism: First step: (S)-3-hydroxy-3-methylglutaryl-CoA + NADPH -> mevaldyl-CoA + NADP+
Second step: mevaldyl-CoA + H2O -> (R)-mevalonate + NADP+
23
Substrates and Reaction Kinetics
Substrate Sp. Property Value Units Standard property Standard value Assay description Assay conditions Comments Reference
(S)-3-hydroxy-3-methylglutaryl-CoA Rn Km 4x10-6 M pKm 5.4 Intestinal enzyme, in vitro assay pH 7.5. 37ºC 61
(S)-3-hydroxy-3-methylglutaryl-CoA Rn Km 6x10-6 M pKm 5.2 purified from rat liver microsomes; in vitro assay pH 7 Km value calculated for S-isomer. 300 nmoles of HMG-CoA is a final volume of 50ml. Racemic mixture of 3-hydroxy-3-methylglutaryl-CoA used in assay 31
(S)-3-hydroxy-3-methylglutaryl-CoA Rn Km 1.2x10-5 M pKm 4.9 purified from rat liver microsomes; in vitro assay pH 7 Observed Km value. (S, R) 3-hydroxy-3-methylglutaryl-CoA used in assay. 300 nmoles of HMG-CoA is a final volume of 50ml. 31
(S)-3-hydroxy-3-methylglutaryl-CoA Mm Km 1.43x10-5 M pKm 4.8 Enzyme purified from mouse liver microsomes, in vitro assay pH 7.4, 37ºC Mice sacrified in the dark. Study considers the effects of light-dark cycle on enzyme expression. Concentrations of substrates: 5mM NADPH, 88-528µM HMG-CoA. Paper does not specify whether the S-isomer of 3-hydroxy-3-methylglutaryl-CoA or a racemic mixture was used in the assay. 43
(S)-3-hydroxy-3-methylglutaryl-CoA Mm Km 2.42x10-5 M pKm 4.6 Enzyme purified from mouse liver microsomes, in vitro assay pH 7.4, 37ºC Mice sacrified in the light. Study considers the effects of light-dark cycle on enzyme expression. Concentrations of substrates: 5mM NADPH, 88-528µM HMG-CoA. Paper does not specify whether the S-isomer of 3-hydroxy-3-methylglutaryl-CoA or a racemic mixture was used in the assay. 43
(S)-3-hydroxy-3-methylglutaryl-CoA Hs Km 7x10-5 M pKm 4.2 Recombinant human enzyme- catalytic portion expressed in E.coli, extracted and purified; in vitro assay pH 6.8, 37°C Concentration of substrates: (S)-3-hydroxy-3-methylglutaryl-CoA varied between 0-400µM, NADPH kept constant at 270µM. Paper does not specify whether the S-isomer of 3-hydroxy-3-methylglutaryl-CoA or a racemic mixture was used in the assay 10
NADPH Hs Km 2.1x10-5 M pKm 4.7 Recombinant human enzyme- catalytic portion expressed in E.coli, extracted and purified; in vitro assay pH 6.8, 37°C Concentration of substrates: NADPH varied between 0-500µM, (S)-3-hydroxy-3-methylglutaryl-CoA kept constant at 100µM 10
(S)-3-hydroxy-3-methylglutaryl-CoA Mm Vmax 1.43x10-4 µmol/min/mg Enzyme purified from mouse liver microsomes, in vitro assay pH 7.4, 37ºC Mice sacrificed in the dark. Concentrations of substrates: 5mM NADPH, 88-528µM HMG-CoA. 43
(S)-3-hydroxy-3-methylglutaryl-CoA Mm Vmax 6.25x10-4 µmol/min/mg Enzyme purified from mouse liver microsomes, in vitro assay pH 7.4, 37ºC Mice sacrificed in the light. Concentrations of substrates: 5mM NADPH, 88-528µM HMG-CoA. 43
(S)-3-hydroxy-3-methylglutaryl-CoA Hs Vmax 5.2 micromol/s Recombinant human enzyme- catalytic portion expressed in E.coli, extracted and purified; in vitro assay. 4nM enzyme is assay mixture pH 6.8, 37°C Concentration of substrates: (S)-3-hydroxy-3-methylglutaryl-CoA varied between 0-400µM, NADPH kept constant at 270µM. Paper does not specify whether the S-isomer of 3-hydroxy-3-methylglutaryl-CoA or a racemic mixture was used in the assay 10
NADPH Hs Vmax 0.03 micromol/s Recombinant human enzyme- catalytic portion expressed in E.coli, extracted and purified; in vitro assay. 4nM enzyme is assay mixture pH 6.8, 37°C Concentration of substrates: NADPH varied between 0-500µM, (S)-3-hydroxy-3-methylglutaryl-CoA kept constant at 100µM 10
Cofactors
Cofactor Species Comments Reference
NADPH Human 10,18,26
NADPH Mouse 49
NADPH Rat 25,34
NADP+ Human 59
NADP+ Mouse 43
NADP+ Rat 36

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Inhibitors
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Ligand Sp. Action Value Parameter Reference
o-hydroxyatorvastatin Rn Inhibition 7.6 pKd 48
pKd 7.6 (Kd 2.74x10-8 M) [48]
lovastatin Hs Competitive 9.2 pKi 2
pKi 9.2 (Ki 6x10-10 M) [2]
Description: Inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: 200µM NADPH, HMG-CoA concentration varied- 17.5µM, 34.8µM or 52.1µM
mevastatin Rn Competitive 8.9 – 9.0 pKi 16,21
pKi 9.0 (Ki 1x10-9 M) [16]
Description: in vitro inhibition of HMG-CoA reductase
Conditions: Assay used the acid form of mevastatin
pKi 8.9 (Ki 1.4x10-9 M) [21]
Conditions: Substrate concentrations: 20µM HMG CoA, 2.1 mM NADP
rosuvastatin Hs Competitive 8.6 pKi 10
pKi 8.6 (Ki 2.3x10-9 M) [10]
Conditions: pH 6.8, concentrations of substrates: 100µM HMG-CoA, 270µM NADPH.
compound 2 [Dreyer et al., 1991] Hs Inhibition 8.5 pKi 14
pKi 8.5 (Ki 3x10-9 M) [14]
cerivastatin Hs Competitive 8.2 pKi 10
pKi 8.2 (Ki 5.7x10-9 M) [10]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: pH 6.8, concentrations of substrates: 100µM HMG-CoA, 270µM NADPH. Human HMG-COA reductase catalytic domain was expressed in Escherichia coli BL(DE3) cells and purified using a GST affinity column.
atorvastatin Hs Competitive 7.8 pKi 10
pKi 7.8 (Ki 1.4x10-8 M) [10]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: pH 6.8, 37°C concentrations of substrates: 100µM HMG-CoA, 270µM NADPH. Human HMG-COA reductase catalytic domain was expressed in Escherichia coli BL(DE3) cells and purified using a GST affinity column.
compound 3 [Dreyer et al., 1991] Hs Inhibition 7.8 pKi 14
pKi 7.8 (Ki 1.6x10-8 M) [14]
DFGYVAE Hs Competitive 7.3 pKi 35
pKi 7.3 (Ki 5.1x10-8 M) [35]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: Varying concentrations of HMG-CoA and NADPH varied at 72, 96, 120 and 144µM.
fluvastatin Hs Competitive 6.6 – 7.6 pKi 10,23
pKi 7.6 (Ki 2.8x10-8 M) [23]
pKi 6.6 (Ki 2.56x10-7 M) [10]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: 100µM HMG-CoA and 270µM NADPH. Human HMG-COA reductase catalytic domain was expressed in Escherichia coli BL(DE3) cells and purified using a GST affinity column.
pravastatin Hs Competitive 7.0 pKi 10
pKi 7.0 (Ki 1.03x10-7 M) [10]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: pH 6.8, concentrations of substrates: 100µM HMG-CoA, 270µM NADPH. Human HMG-COA reductase catalytic domain was expressed in Escherichia coli BL(DE3) cells and purified using a GST affinity column.
pitavastatin Rn Inhibition 5.1 pKi 63
pKi 5.1 (Ki 8.9x10-6 M) [63]
Description: Note this assay used the pitavastatin calcium salt.
pravastatin Rn Competitive 8.4 pEC50 56
pEC50 8.4 (IC50 4.2x10-9 M) [56]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: In vitro HMG-CoA reductase inhibitory activity to inhibit sterol synthesis in cell free system in rat
rosuvastatin Rn Competitive 9.8 pIC50 33
pIC50 9.8 (IC50 1.6x10-10 M) [33]
Description: Inhibition of cholesterol systhesis
Conditions: Inhibition of cholesterol synthesis in primary rat hepatocytes
compound 33 [PMID: 17574412] Hs Inhibition 9.7 pIC50 42
pIC50 9.7 (IC50 2x10-10 M) [42]
Description: Inhibition of HMG-CoA reductase
compound 2d [PMID: 2153213] Hs Inhibition 9.6 pIC50 28
pIC50 9.6 (IC50 2.7x10-10 M) [28]
Description: Inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: NADP 50mM, 0.91 mM HMG-CoA. In cultures of hepatic cells (HEP G2, a human hepatoma cell line)
compound 3h [PMID: 8246234] Rn Inhibition 9.5 pIC50 44
pIC50 9.5 (IC50 3x10-10 M) [44]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: Rat liver microsomal preparation
compound 41 [PMID: 17574411] Hs Inhibition 9.5 pIC50 41
pIC50 9.5 (IC50 3x10-10 M) [41]
Description: Inhibition of HMG-CoA reductase
compound 13b [PMID: 18412317] Rn Inhibition 9.3 pIC50 1
pIC50 9.3 (IC50 5x10-10 M) [1]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: Rat hepatic microsomes, measuring [14C]HMG-CoA to [14C]mevalonic acid
compound 11jj [PMID: 1656041] Hs Inhibition 9.3 pIC50 29
pIC50 9.3 (IC50 5x10-10 M) [29]
Description: Inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: 0.91mM HMG-CoA, 50mM NADP. Inhibition of the incorporation of sodium [14C]-acetate into cholesterol in HEP G2 cells.
compound 4p [PMID: 1895299] Rn Inhibition 9.3 pIC50 45
pIC50 9.3 (IC50 5.5x10-10 M) [45]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: 2.7mM NADPH, 0.05µCi HMG-CoA.
compound 2c [PMID: 2153213] Hs Inhibition 9.2 pIC50 28
pIC50 9.2 (IC50 5.7x10-10 M) [28]
Description: Inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: NADP 50mM, 0.91 mM HMG-CoA. In cultures of hepatic cells (HEP G2, a human hepatoma cell line)
compound 1a [PMID: 2153213] Hs Inhibition 9.1 pIC50 28
pIC50 9.1 (IC50 8.3x10-10 M) [28]
Description: Inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: NADP 50mM, 0.91 mM HMG-CoA. In cultures of hepatic cells (HEP G2, a human hepatoma cell line)
compound 29f [PMID: 17560788] Rn Inhibition 9.1 pIC50 9
pIC50 9.1 (IC50 8.5x10-10 M) [9]
Description: Inhibition of HMG-CoA reductase
Conditions: assessed by measuring cholesterol synthesis after 30 mins
compound 2g [PMID: 2296036] Rn Inhibition 9.0 pIC50 6
pIC50 9.0 (IC50 1x10-9 M) [6]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: Concentration of substrates: NADP=50mM HMG-CoA=0.91mM. Rat liver enzyme
compound 74 [PMID: 1656041] Rn Inhibition 9.0 pIC50 29
pIC50 9.0 (IC50 1x10-9 M) [29]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: 0.91mM HMG-CoA, 50mM NADP. Crude rat liver (solubilized enzyme )
compound 28 [PMID: 8246233] Rn Inhibition 9.0 pIC50 11
pIC50 9.0 (IC50 1x10-9 M) [11]
Description: Inhibition of HMG-CoA reductase
Conditions: 225nmol of NADP+ and 2.5nmol HMG-CoA in a volume of 25µL. Inhibitory activity against washed rat liver microsomal HMG-CoA reductase (HMGR)
compound 5ab [PMID: 8246233] Rn Inhibition 9.0 pIC50 11
pIC50 9.0 (IC50 1x10-9 M) [11]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: 225nmol of NADP+ and 2.5nmol HMG-CoA in a volume of 25µL. Washed rat liver microsomal HMG-CoA reductase
compound 16f [PMID: 18155906] Rn Inhibition 9.0 pIC50 37
pIC50 9.0 (IC50 1x10-9 M) [37]
Description: Inhibition of HMGCoA reductase
Conditions: Inhibition of rat microsomal HMGCoA reductase
5-ketodihydromevinolin Rn Inhibition 9.0 pIC50 21
pIC50 9.0 (IC50 1x10-9 M) [21]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: 21mM NADP, 20µM HMG-CoA. Inhibition of HMG-CoA reductase in rat liver microsomes
atorvastatin Rn Competitive 8.9 pIC50 33
pIC50 8.9 (IC50 1.16x10-9 M) [33]
Description: in vitro inhibition of cholesterol synthesis
Conditions: Inhibition IC50 values measured in primary rat hepatocytes
compound 3j [PMID: 2231594] Rn Inhibition 8.9 pIC50 30
pIC50 8.9 (IC50 1.2x10-9 M) [30]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: Concentration of substrates: 100µM HMGCoA and 2.7 mM NADPH. Inhibition of rat microsomal HMG-CoA reductase activity by 50%
compound 6v [PMID: 1895299] Rn Inhibition 8.9 pIC50 45
pIC50 8.9 (IC50 1.2x10-9 M) [45]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: 2.7mM NADPH, 0.05µCi HMG-CoA.
compound 7 [PMID: 2909732] Rn Inhibition 8.9 pIC50 20
pIC50 8.9 (IC50 1.3x10-9 M) [20]
Description: Inhibition of HMG-CoA reductase
Conditions: rat liver microsomes
compound 50 [PMID: 18072721] Rn Inhibition 8.8 pIC50 40
pIC50 8.8 (IC50 1.5x10-9 M) [40]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: 0.024µCi, 15mM NADPH. Inhibition of HMG-CoA redcutase in Sprague-Dawley rat liver microsomes
compound 4ff [PMID: 1656041] Hs Inhibition 8.8 pIC50 29
pIC50 8.8 (IC50 1.8x10-9 M) [29]
Description: Inhibition of cellular activity
Conditions: Substrate concentrations: 0.91mM HMG-CoA, 50mM NADP. Inhibition of the incorporation of sodium [14C]-acetate into cholesterol in HEP G2 cells.
compound 3q [PMID: 2231594] Rn Inhibition 8.7 pIC50 30
pIC50 8.7 (IC50 1.9x10-9 M) [30]
Description: Inhibition of HMG-CoA reductase
Conditions: Concentration of substrates: 100µM HMGCoA and 2.7 mM NADPH. Inhibition of rat microsomal HMG-CoA reductase activity by 50%
compound 42 [PMID: 17574411] Hs Inhibition 8.7 pIC50 41
pIC50 8.7 (IC50 1.9x10-9 M) [41]
Description: Inhibition of HMG-CoA reductase
compound 3u [PMID: 2231594] Rn Inhibition 8.7 pIC50 30
pIC50 8.7 (IC50 2.1x10-9 M) [30]
Description: Inhibition of HMG-CoA reductase
Conditions: Concentration of substrates: 100µM HMGCoA and 2.7 mM NADPH. Inhibition of rat microsomal HMG-CoA reductase activity by 50%
compound 13g [PMID: 2153213] Rn Inhibition 8.6 pIC50 28
pIC50 8.6 (IC50 2.5x10-9 M) [28]
Description: Inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: NADP 50mM, 0.91 mM HMG-CoA. Rat liver HMG-CoA reductase
compound 35 [PMID: 8246233] Rn Inhibition 8.6 pIC50 11
pIC50 8.6 (IC50 2.6x10-9 M) [11]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: 225nmol of NADP+ and 2.5nmol HMG-CoA in a volume of 25µL. Washed rat liver microsomal HMG-CoA reductase
compound 11ff [PMID: 1656041] Rn Inhibition 8.6 pIC50 29
pIC50 8.6 (IC50 2.7x10-9 M) [29]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: 0.91mM HMG-CoA, 50mM NADP. In vitro inhibition of HMG-CoA reductase in solubilized rat liver.
compound 4d [PMID: 2296036] Rn Inhibition 8.5 pIC50 6
pIC50 8.5 (IC50 3x10-9 M) [6]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: Concentration of substrates: NADP=50mM HMG-CoA=0.91mM. Rat liver enzyme
compound 18t [PMID: 8246237] Rn Inhibition 8.5 pIC50 12
pIC50 8.5 (IC50 3x10-9 M) [12]
Description: Inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: 2.8mM NADPH, 0.1 mM HMG-CoA. Inhibitory activity against partially purified rat liver HMG-CoA reductase in vitro.
compound 13b [PMID: 2153213] Rn Inhibition >8.5 pIC50 28
pIC50 >8.5 (IC50 <3x10-9 M) [28]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: NADP 50mM, 0.91 mM HMG-CoA.. Cellular HMG-CoA reductase in cultures of hepatic cells (HEP G2, a human hepatoma cell line)
fluvastatin Rn Competitive 8.4 – 8.6 pIC50 12,24,29,33
pIC50 8.6 (IC50 2.5x10-9 M) [12]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: 2.8mM NADPH, 0.1 mM HMG-CoA. Partially purified microsomal preparations
pIC50 8.6 (IC50 2.5x10-9 M) [29]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: Crude rat liver (solubilized enzyme )
pIC50 8.5 (IC50 3x10-9 M) [24]
Description: in vitro inhibition of HMG-CoA reductase
Conditions: DL-[3-14C]3-hydroxy-3-methylglutaryl-CoA (0.37 MBq) and 10 mg protein of microsomal fraction incubated at 37°C for 30 min The reaction was terminated by addition of 2 M HCl aq and the metabolites were converted to mevalonolactone. The metabolite mixture was separated by means of thin layer chromatography (Merck 20 TLC plates Silica Gel 60 F254) with acetone/benzene (1:1 v/v). The radioactivity of each spot on the plate was measured with a bioimaging analyzer (FLA-7000, Fuji Film, Japan).
pIC50 8.4 (IC50 3.78x10-9 M) [33]
Description: in vitro inhibition of cholesterol synthesis
Conditions: Inhibition IC50 values measured in primary rat hepatocytes
dalvastatin Rn Inhibition 8.5 pIC50 3
pIC50 8.5 (IC50 3.4x10-9 M) [3]
Description: Rat liver HMG-CoA reductase inhibition assay.
cerivastatin Rn Competitive 8.4 pIC50 33
pIC50 8.4 (IC50 3.54x10-9 M) [33]
Description: in vitro inhibition of cholesterol synthesis
Conditions: Inhibition IC50 values measured in primary rat hepatocytes
compound 3k [PMID: 2231594] Rn Inhibition 8.4 pIC50 30
pIC50 8.4 (IC50 3.8x10-9 M) [30]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: Concentration of substrates: 100µM HMGCoA and 2.7 mM NADPH. Inhibition of rat microsomal HMG-CoA reductase activity by 50%
compound 1 [PMID: 1895299] Rn Inhibition 8.4 pIC50 45
pIC50 8.4 (IC50 4x10-9 M) [45]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: 2.7mM NADPH, 0.05µCi HMG-CoA. The compound was tested in vitro for inhibition of rat hepatic HMG-CoA reductase.
rosuvastatin Hs Competitive 8.3 – 8.5 pIC50 27,33,42
pIC50 8.5 (IC50 3.1x10-9 M) [42]
Description: Inhibition of HMG-CoA reductase
pIC50 8.3 (IC50 5x10-9 M) [27]
pIC50 8.3 (IC50 5.4x10-9 M) [33]
Description: in vitro inhibition of cholesterol synthesis
Conditions: Inhibition IC50 values measured in primary rat hepatocytes
compound 2t [PMID: 2296036] Hs Inhibition 8.3 pIC50 6
pIC50 8.3 (IC50 4.8x10-9 M) [6]
Description: Inhibition of HMG-CoA reductase
Conditions: Concentration of substrates: NADP=50mM HMG-CoA=0.91mM. Inhibition of cellular HMG-CoA reductase in cultures of human HEP G2 cells, determined by decreased incorporation of sodium [14C]-acetate into cholesterol.
compound 18 [PMID: 1875346] Rn Inhibition 8.3 pIC50 15
pIC50 8.3 (IC50 5x10-9 M) [15]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: In vitro ability to inhibit solubilized, partially purified, rat liver HMG-CoA reductase
compound 9 [PMID: 1992149] Rn Inhibition 8.2 pIC50 47
pIC50 8.2 (IC50 6.6x10-9 M) [47]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: Rat liver HMG-CoA reductase
atorvastatin lactone Rn Inhibition 8.2 pIC50 46
pIC50 8.2 (IC50 6.99x10-9 M) [46]
Description: Inhibition of HMG-CoA reductase
Conditions: Inhibition of HMG-CoA reductase activity in partially purified rat liver
compound 9 [PMID: 1992149] Hs Inhibition 8.2 pIC50 51
pIC50 8.2 (IC50 6.99x10-9 M) [51]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: 0.45µM HMG-CoA, 4mM NADPH. Partially purified microsomal preparations
atorvastatin Hs Competitive 8.1 pIC50 27
pIC50 8.1 (IC50 8x10-9 M) [27]
compound 1 [Patel et al., 1991] Hs Inhibition 8.1 pIC50 38
pIC50 8.1 (IC50 8x10-9 M) [38]
Description: In vitro inhibition of HMG-CoA reductase
pravastatin Rn Competitive 7.9 – 8.3 pIC50 33,40,44
pIC50 8.3 (IC50 5x10-9 M) [44]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: Sodium salt of pravastatin was tested for the inhibition of rat liver microsomal HMG-CoA reductase.
pIC50 8.2 (IC50 6.93x10-9 M) [33]
Description: in vitro inhibition of cholesterol synthesis
Conditions: Inhibition IC50 values measured in primary rat hepatocytes
pIC50 7.9 (IC50 1.3x10-8 M) [40]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: Concentration of substrate: 0.024µCi HMG-CoA, 15mM NADPH. Inhibition of HMG-CoA redcutase in Sprague-Dawley rat liver microsomes
cerivastatin Hs Competitive 8.0 pIC50 57
pIC50 8.0 (IC50 1x10-8 M) [57]
Description: Inhibition of HMG-CoA reductase
Conditions: Inhibitory concentration against 3-hydroxy-3-methylglutaryl-CoA reductase (check paper for primary source )
simvastatin Hs Competitive 7.9 – 8.0 pIC50 19,27
pIC50 8.0 (IC50 1.1x10-8 M) [27]
pIC50 7.9 (IC50 1.21x10-8 M) [19]
Description: In vitro inhibition of HMG-CoA reductase
simvastatin Rn Competitive 6.8 – 9.1 pIC50 22,33,42
pIC50 9.1 (IC50 9x10-10 M) [22]
Description: Inhibition of HMG-CoA reductase
Conditions: Concentration of substrate:12.5 µM HMG-CoA. Inhibition of solubilized, purified rat liver HMG-CoA reductase.
pIC50 8.9 (IC50 1.3x10-9 M) [42]
Description: In vitro inhibition of cellular cholesterol synthesis
Conditions: Assay measuring sterol biosynthesis (cell assay) in rat hepatocytes at 37°C
pIC50 8.6 (IC50 2.74x10-9 M) [33]
Description: in vitro inhibition of cholesterol synthesis
Conditions: Inhibition IC50 values measured in primary rat hepatocytes
pIC50 7.3 (IC50 4.9x10-8 M) [42]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: Assay using purified enzyme, 37oC
pIC50 6.8 (IC50 1.5x10-7 M) [42]
Description: In vitro inhibition of cellular cholesterol synthesis
Conditions: Assay measuring sterol biosynthesis (cell assay) in rat myocytes at 37°C
BMY-21950 Rn Inhibition 7.9 pIC50 47
pIC50 7.9 (IC50 1.3x10-8 M) [47]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: Rat liver HMG-CoA reductase
compound 2f [PMID: 2153213] Hs Inhibition 7.7 pIC50 28
pIC50 7.7 (IC50 1.8x10-8 M) [28]
Description: Inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: NADP 50mM, 0.91 mM HMG-CoA. In cultures of hepatic cells (HEP G2, a human hepatoma cell line)
mevastatin Hs Competitive 7.6 pIC50 57
pIC50 7.6 (IC50 2.3x10-8 M) [57]
Conditions: this is a modelling paper and data may have extracted from another source- please check
BMY 22089 Rn Inhibition 7.6 pIC50 50
pIC50 7.6 (IC50 2.4x10-8 M) [50]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: 0.33 mM, NADPH 3.0mM. In vitro inhibitory activity was measured against rat liver HMG-CoA reductase using [2-14C]-acetate incorporation
compound 8b [PMID: 1992138] Rn Inhibition 7.6 pIC50 52
pIC50 7.6 (IC50 2.5x10-8 M) [52]
Description: Inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: 0.45 microM HMG-CoA, 4mM NADPH. Compound was evaluated for the inhibition of HMG-CoA reductase (COR) in rats.
lovastatin Mm Competitive 7.6 pIC50 7
pIC50 7.6 (IC50 2.7x10-8 M) [7]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: Isolated enzyme HMG-CoA reductase
fluvastatin Hs Competitive 7.6 pIC50 27
pIC50 7.6 (IC50 2.8x10-8 M) [27]
Description: Inhibition of HMG-CoA reductase
compound 25 [PMID: 2296027] Rn Inhibition 7.5 pIC50 53
pIC50 7.5 (IC50 3.2x10-8 M) [53]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: 0.45µM HMG-CoA, 4mM NADPH. In vitro inhibitory activity against HMG-CoA reductase by employing a crude liver homogenate derived from rats fed a chow diet containing 5% cholestyramine
lovastatin Hs Competitive 7.3 – 7.7 pIC50 28,51
pIC50 7.7 (IC50 2x10-8 M) [51]
Description: in vitro inhition of HMG-CoA reductase
Conditions: Inhibitory activity assay used partially purified microsomal preparations.
pIC50 7.3 (IC50 5x10-8 M) [28]
Description: in vitro inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: NADP 50mM, 0.91 mM HMG-CoA. Inhibition of cellular HMG-CoA reductase in cultures of hepatic cells (HEP G2, a human hepatoma cell line)
lovastatin Rn Competitive 6.3 – 8.5 pIC50 7,13,28-29,44,52
pIC50 8.5 (IC50 3x10-9 M) [44]
Description: in vitro inhition of HMG-CoA reductase
Conditions: Inhibition of rat liver microsomal HMG-CoA reductase. Sodium salt preparation used.
pIC50 8.1 (IC50 8x10-9 M) [28]
Description: in vitro inhibition of HMG-CoA reductase
Conditions: In vitro inhibition of HMG-CoA reductase in solubilized rat liver.
pIC50 8.1 (IC50 8x10-9 M) [29]
Description: in vitro inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: 0.91mM HMG-CoA, 50mM NADP. Inhibition of HMG-CoA reductase in solubilized rat liver.
pIC50 8.0 (IC50 1.1x10-8 M) [7]
Description: in vitro inhibition of HMG-CoA reductase
Conditions: Inhibition of microsomal rat liver HMG-CoA reductase
pIC50 7.6 (IC50 2.7x10-8 M) [52]
Description: in vitro inhition of HMG-CoA reductase
Conditions: Substrate concentrations: 0.45 µM HMG-CoA, 4mM NADPH. Compound was evaluated for the inhibition of HMG-CoA reductase (COR) in rats.
pIC50 6.8 (IC50 1.6x10-7 M) [13]
Description: in vitro inhition of HMG-CoA reductase
Conditions: The Na+ salt of mevinoline was tested for HMG-CoA reductase inhibitory activity in a microsomal preparation
pIC50 6.3 (IC50 5.3x10-7 M) [13]
Description: in vitro inhition of HMG-CoA reductase
Conditions: The lactone form of lovastatin was tested for HMG-CoA reductase inhibitory activity in a microsomal preparation
compound 1e [PMID: 2153213] Hs Inhibition 7.3 pIC50 28
pIC50 7.3 (IC50 5x10-8 M) [28]
Description: Inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: NADP 50mM, 0.91 mM HMG-CoA.. In cultures of hepatic cells (HEP G2, a human hepatoma cell line)
compound 11nn [PMID: 1656041] Rn Inhibition 7.3 pIC50 29
pIC50 7.3 (IC50 5x10-8 M) [29]
Description: Inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: 0.91mM HMG-CoA, 50mM NADP. In vitro inhibition of HMG-CoA reductase in solubilized rat liver.
compound 17 [PMID: 3701793] Rn Inhibition 7.1 pIC50 54
pIC50 7.1 (IC50 8.5x10-8 M) [54]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: Substrate concentration: 12.5µM HMG-CoA. HMG-CoA rat liver HMG-CoA reductase
compound 29 [PMID: 15686906] Hs Inhibition 7.0 pIC50 57
pIC50 7.0 [57]
Description: Inhibition of HMG-CoA reductase
mevastatin Rn Competitive 5.9 – 8.0 pIC50 5,13,24,46,52,55
pIC50 8.0 (IC50 1x10-8 M) [55]
Description: in vitro inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: 3mM NADP, 0.2mM HMG-CoA. The sodium salt of compactin was tested using HMG-CoA enzyme purified from rat microsomal preparations.
pIC50 7.6 (IC50 2.5x10-8 M) [52]
Description: in vitro inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: 0.45 µM HMG-CoA, 4mM NADPH
pIC50 7.5 (IC50 3x10-8 M) [46]
Description: in vitro inhibition of HMG-CoA reductase
Conditions: Inhibition of HMG-CoA reductase activity in partially purified rat liver
pIC50 7.4 (IC50 4x10-8 M) [24]
Description: in vitro inhibition of HMG-CoA reductase
Conditions: DL-[3-14C]3-hydroxy-3-methylglutaryl-CoA (0.37 MBq) and 10 mg protein of microsomal fraction incubated at 37°C for 30 min The reaction was terminated by addition of 2 M HCl aq and the metabolites were converted to mevalonolactone. The metabolite mixture was separated by means of thin layer chromatography (Merck 20 TLC plates Silica Gel 60 F254) with acetone/benzene (1:1 v/v). The radioactivity of each spot on the plate was measured with a bioimaging analyzer (FLA-7000, Fuji Film, Japan).
pIC50 7.0 (IC50 1.1x10-7 M) [13]
Description: in vitro inhibition of HMG-CoA reductase
Conditions: Compactin (as a Na+ salt) was tested in an in vitro assay for the HMG-CoA reductase inhibitory activity in a microsomal preparation
pIC50 6.0 (IC50 1x10-6 M) [5]
Conditions: Inhibition of HMG-CoA reductase from rat liver
pIC50 6.0 (IC50 1x10-6 M) [5]
Description: in vitro inhibition of HMG-CoA reductase
Conditions: Inhibition of rat liver microsomal HMG-CoA reductase
pIC50 5.9 (IC50 1.15x10-6 M) [13]
Description: in vitro inhibition of HMG-CoA reductase
Conditions: Compactin (as lactone) was tested in an in vitro assay for the HMG-CoA reductase inhibitory activity in a microsomal preparation
compound 1f [PMID: 2153213] Hs Inhibition 7.0 pIC50 28
pIC50 7.0 (IC50 1.06x10-7 M) [28]
Description: Inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: NADP 50mM, 0.91 mM HMG-CoA. In cultures of hepatic cells (HEP G2, a human hepatoma cell line)
compound 25d [PMID: 19502059] Rn Inhibition 6.8 pIC50 24
pIC50 6.8 (IC50 1.5x10-7 M) [24]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: Inhibition of rat HMG-CoA reductase using 0.37 MBq DL-[3-14C]HMG-CoA
compound 29 [PMID: 2296027] Rn Inhibition 6.8 pIC50 53
pIC50 6.8 (IC50 1.58x10-7 M) [53]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: 0.45µM HMG-CoA, 4mM NADPH. In vitro inhibitory activity against HMG-CoA reductase by employing a crude liver homogenate derived from rats fed a chow diet containing 5% cholestyramine
DFGYVAE Hs Competitive 6.8 pIC50 35
pIC50 6.8 (IC50 1.6x10-7 M) [35]
Description: Inhibition of HMG-CoA reductase
Conditions: Varying concentrations of HMG-CoA and NADPH varied at 72, 96, 120 and 144µM. Inhibition of HMG-CoA reductase by spectrophotometry
compound 9 [PMID: 7932551] Rn Inhibition 6.7 pIC50 58
pIC50 6.7 (IC50 2x10-7 M) [58]
Description: Inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: 36 nCi (1.3 kBq) HMG-CoA, NADP 3mM. Rat liver microsomes
pravastatin Hs Competitive 5.9 – 7.5 pIC50 51,56
pIC50 7.5 (IC50 3x10-8 M) [51]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: Concentrations of substrates: 0.45 µM HMG-CoA, 4mM NADPH. Tested in vitro for the inhibition of HMG-CoA reductase from partially purified microsomal preparations.
pIC50 5.9 (IC50 1.37x10-6 M) [56]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: cellular assay testing the inhibition of steroidogenesis in Hep G2 cells (human hepatoma cell line)
compound 11nn [PMID: 1656041] Hs Inhibition 6.6 pIC50 29
pIC50 6.6 (IC50 2.5x10-7 M) [29]
Description: Inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: 0.91mM HMG-CoA, 50mM NADP. Inhibition of the incorporation of sodium [14C]-acetate into cholesterol in HEP G2 cells.
compound 4i [PMID: 2296036] Hs Inhibition 6.4 pIC50 6
pIC50 6.4 (IC50 3.7x10-7 M) [6]
Description: Inhibition of HMG-CoA reductase
Conditions: Concentration of substrates: NADP=50mM HMG-CoA=0.91mM. Inhibition of cellular HMG-CoA reductase in cultures of human HEP G2 cells, determined by decreased incorporation of sodium [14C]-acetate into cholesterol.
compound 11dd [PMID: 1656041] Rn Inhibition 6.4 pIC50 29
pIC50 6.4 (IC50 3.8x10-7 M) [29]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: 0.91mM HMG-CoA, 50mM NADP. Solubilized rat liver
compound 13 [PMID: 1992149] Rn Inhibition 6.3 pIC50 47
pIC50 6.3 (IC50 4.8x10-7 M) [47]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: Ability to inhibit microsomal preparation of HMG-CoA reductase in rat liver.
compound 6a [Patil et al., 1989] Hs Inhibition 6.3 pIC50 39
pIC50 6.3 (IC50 5x10-7 M) [39]
Description: Inhibition of HMGCoA reductase
compound 18 [PMID: 8426367] Hs Inhibition 6.0 pIC50 17
pIC50 6.0 (IC50 1x10-6 M) [17]
Description: Inhibition of HMG-CoA reductase
Conditions: HMG-coA expressed in CHO cells
compound 4rr [PMID: 1656041] Rn Inhibition <6.0 pIC50 29
pIC50 <6.0 (IC50 >1x10-6 M) [29]
Description: Inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: 0.91mM HMG-CoA, 50mM NADP. Solubilized rat liver
compound 29 [PMID: 1527791] Hs Inhibition 5.8 pIC50 8
pIC50 5.8 (IC50 1.4x10-6 M) [8]
Description: Inhibition of HMG-CoA reductase
Conditions: Concentration required to inhibit HMG-CoA reductase by 50% was determined in Hep G2 cell line
FPYVAE peptide [PMID: 20494585] Hs Inhibition 5.8 pIC50 35
pIC50 5.8 (IC50 1.47x10-6 M) [35]
Description: In vitro inhibition of HMG-CoA reductase
Conditions: Varying concentrations of HMG-CoA and NADPH varied at 72, 96, 120 and 144µM. Spectrophotometric assay used.
compound 17 [PMID: 15686906] Hs Inhibition 5.7 pIC50 57
pIC50 5.7 [57]
Description: Inhibition of HMG-CoA reductase
compound 4 [Balasubramanian et al., 1992] Rn Inhibition 5.4 pIC50 4
pIC50 5.4 (IC50 4.1x10-6 M) [4]
compound 9a [Patil et al., 1989] Hs Inhibition 5.3 pIC50 39
pIC50 5.3 (IC50 5x10-6 M) [39]
Description: Inhibition of HMG-CoA reductase
GLPDGG peptide [PMID: 20494585] Hs Inhibition 4.7 pIC50 35
pIC50 4.7 (IC50 2.231x10-5 M) [35]
Description: Inhibition of HMG-CoA reductase
Conditions: Varying concentrations of HMG-CoA and NADPH used at concentrations of 72, 96, 120 and 144 µM. Inhibition of HMG-CoA reductase by spectrophotometry
View species-specific inhibitor tables
Inhibitor Comments
The inhibition of HMG-CoA reductase by rosuvastatin is competitive with respect to the substrate HMG-CoA , and noncompetitive with respect to co-substrate NADPH [33]. IC50 values of rosuvastatin have been shown to vary according to whether a cell-free system of cell-culture based assay is used [56].

Some of the inhibitors above have been selected as representative structures from sets of stucturally similar compounds with bioactivity data at this target on ChEMBLdb.

Click here for a summary of the ChEMBL bioactivity data 


Tissue Distribution
Gallbladder
Species:  Human
Technique:  Microarray analysis
References:  62
Liver, brain, heart, spleen, kidney
Species:  Human
Technique:  RT-PCR
References:  60

References

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1. Ahmad S, Madsen CS, Stein PD, Janovitz E, Huang C, Ngu K, Bisaha S, Kennedy LJ, Chen BC, Zhao R et al.. (2008) (3R,5S,E)-7-(4-(4-fluorophenyl)-6-isopropyl-2-(methyl(1-methyl-1h-1,2,4-triazol-5-yl)amino)pyrimidin-5-yl)-3,5-dihydroxyhept-6-enoic acid (BMS-644950): a rationally designed orally efficacious 3-hydroxy-3-methylglutaryl coenzyme-a reductase inhibitor with reduced myotoxicity potential. J. Med. Chem., 51 (9): 2722-33. [PMID:18412317]

2. Alberts AW, Chen J, Kuron G, Hunt V, Huff J, Hoffman C, Rothrock J, Lopez M, Joshua H, Harris E et al.. (1980) Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agent. Proc. Natl. Acad. Sci. U.S.A., 77 (7): 3957-61. [PMID:6933445]

3. Amin D, Gustafson SK, Weinacht JM, Cornell SA, Neuenschwander K, Kosmider B, Scotese AC, Regan JR, Perrone MH. (1993) RG 12561 (dalvastatin): a novel synthetic inhibitor of HMG-CoA reductase and cholesterol-lowering agent. Pharmacology, 46 (1): 13-22. [PMID:8434028]

4. Balasubramanian N, Brown PJ, Parker RA, Wright JJ. (1992) HMG-CoA Reductase Inhibitors 4. Tetrazole series: Conformational contraints and structural requirements at the hydrophobic domain. Bioorg. Med. Chem. Lett, 2 (1): 99-104.

5. Baran JS, Laos I, Langford DD, Miller JE, Jett C, Taite B, Rohrbacher E. (1985) 3-Alkyl-3-hydroxyglutaric acids: a new class of hypocholesterolemic HMG CoA reductase inhibitors. 1. J. Med. Chem., 28 (5): 597-601. [PMID:3989819]

6. Beck G, Kesseler K, Baader E, Bartmann W, Bergmann A, Granzer E, Jendralla H, von Kerekjarto B, Krause R, Paulus E. (1990) Synthesis and biological activity of new HMG-CoA reductase inhibitors. 1. Lactones of pyridine- and pyrimidine-substituted 3,5-dihydroxy-6-heptenoic (-heptanoic) acids. J. Med. Chem., 33 (1): 52-60. [PMID:2296036]

7. Bone EA, Cunningham EM, Davidson AH, Galloway WA, Lewis CN, Morrice EM, Reeve M, Todd RS, White IM. (1992) The design and biological evaluation of a series of 3-hydroxy-3-methylglutaryl coenzyme a (HMG-CoA) reductase inhibitors related to dihydromevinolin. Bioorg. Med. Chem. Lett., 2 (3): 223-228.

8. Bone EA, Davidson AH, Lewis CN, Todd RS. (1992) Synthesis and biological evaluation of dihydroeptastatin, a novel inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. J. Med. Chem., 35 (18): 3388-93. [PMID:1527791]

9. Bratton LD, Auerbach B, Choi C, Dillon L, Hanselman JC, Larsen SD, Lu G, Olsen K, Pfefferkorn JA, Robertson A et al.. (2007) Discovery of pyrrole-based hepatoselective ligands as potent inhibitors of HMG-CoA reductase. Bioorg. Med. Chem., 15 (16): 5576-89. [PMID:17560788]

10. Carbonell T, Freire E. (2005) Binding thermodynamics of statins to HMG-CoA reductase. Biochemistry, 44 (35): 11741-8. [PMID:16128575]

11. Chan C, Bailey EJ, Hartley CD, Hayman DF, Hutson JL, Inglis GG, Jones PS, Keeling SE, Kirk BE, Lamont RB. (1993) Inhibitors of cholesterol biosynthesis. 1. 3,5-Dihydroxy-7-(N-imidazolyl)-6-heptenoates and -heptanoates, a novel series of HMG-CoA reductase inhibitors. J. Med. Chem., 36 (23): 3646-57. [PMID:8246233]

12. Connolly PJ, Westin CD, Loughney DA, Minor LK. (1993) HMG-CoA reductase inhibitors: design, synthesis, and biological activity of tetrahydroindazole-substituted 3,5-dihydroxy-6-heptenoic acid sodium salts. J. Med. Chem., 36 (23): 3674-85. [PMID:8246237]

13. Coppola GM, Damon RE, Yu H, Engstrom RG, Scallen TJ. (1997) Design and biological evaluation of a series of thiophene-based 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors. Bioorganic & Medicinal Chemistry Letters, 7 (4): 549-554.

14. Dreyer GB, Garvie CT, Metcalf BW, Meek TD, Mayer RJ. (1991) Phosphinic acid inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme a reductase. Bioorg. Med. Chem. Lett., 1 (3): 152-154.

15. Duggan ME, Alberts AW, Bostedor R, Chao YS, Germershausen JI, Gilfillan JL, Halczenko W, Hartman GD, Hunt V, Imagire JS. (1991) 3-Hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors. 7. Modification of the hexahydronaphthalene moiety of simvastatin: 5-oxygenated and 5-oxa derivatives. J. Med. Chem., 34 (8): 2489-95. [PMID:1875346]

16. Endo A. (1985) Compactin (ML-236B) and related compounds as potential cholesterol-lowering agents that inhibit HMG-CoA reductase. J. Med. Chem., 28 (4): 401-5. [PMID:3981532]

17. Frye LL, Cusack KP, Leonard DA. (1993) 32-Methyl-32-oxylanosterols: dual-action inhibitors of cholesterol biosynthesis. J. Med. Chem., 36 (3): 410-6. [PMID:8426367]

18. Gueguen Y, Ferrari L, Souidi M, Batt AM, Lutton C, Siest G, Visvikis S. (2007) Compared effect of immunosuppressive drugs cyclosporine A and rapamycin on cholesterol homeostasis key enzymes CYP27A1 and HMG-CoA reductase. Basic Clin. Pharmacol. Toxicol., 100 (6): 392-7. [PMID:17516993]

19. Hartman GD, Halczenko W, Duggan ME, Imagire JS, Smith RL, Pitzenberger SM, Fitzpatrick SL, Alberts AW, Bostedor R, Chao YS. (1992) 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. 9. The synthesis and biological evaluation of novel simvastatin analogs. J. Med. Chem., 35 (21): 3813-21. [PMID:1433193]

20. Heathcock CH, Davis BR, Hadley CR. (1989) Synthesis and biological evaluation of a monocyclic, fully functional analogue of compactin. J. Med. Chem., 32 (1): 197-202. [PMID:2909732]

21. Heathcock CH, Hadley CR, Rosen T, Theisen PD, Hecker SJ. (1987) Total synthesis and biological evaluation of structural analogues of compactin and dihydromevinolin. J. Med. Chem., 30 (10): 1858-73. [PMID:3656359]

22. Hoffman WF, Alberts AW, Anderson PS, Chen JS, Smith RL, Willard AK. (1986) 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. 4. Side chain ester derivatives of mevinolin. J. Med. Chem., 29 (5): 849-52. [PMID:3634830]

23. Holdgate GA, Ward WH, McTaggart F. (2003) Molecular mechanism for inhibition of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase by rosuvastatin. Biochem. Soc. Trans., 31 (Pt 3): 528-31. [PMID:12773150]

24. Hosoda S, Matsuda D, Tomoda H, Hashimoto M, Aoyama H, Hashimoto Y. (2009) Application of a 3,3-diphenylpentane skeleton as a multi-template for creation of HMG-CoA reductase inhibitors. Bioorg. Med. Chem. Lett., 19 (15): 4228-31. [PMID:19502059]

25. Ingebritsen TS, Parker RA, Gibson DM. (1981) Regulation of liver hydroxymethylglutaryl-CoA reductase by a bicyclic phosphorylation system. J. Biol. Chem., 256 (3): 1138-44. [PMID:6256385]

26. Istvan ES, Deisenhofer J. (2000) The structure of the catalytic portion of human HMG-CoA reductase. Biochim. Biophys. Acta, 1529 (1-3): 9-18. [PMID:11111074]

27. Istvan ES, Deisenhofer J. (2001) Structural mechanism for statin inhibition of HMG-CoA reductase. Science, 292 (5519): 1160-4. [PMID:11349148]

28. Jendralla H, Baader E, Bartmann W, Beck G, Bergmann A, Granzer E, von Kerekjarto B, Kesseler K, Krause R, Schubert W. (1990) Synthesis and biological activity of new HMG-CoA reductase inhibitors. 2. Derivatives of 7-(1H-pyrrol-3-yl)-substituted-3,5-dihydroxyhept-6(E)-enoic (-heptanoic) acids. J. Med. Chem., 33 (1): 61-70. [PMID:2153213]

29. Jendralla H, Granzer E, von Kerekjarto B, Krause R, Schacht U, Baader E, Bartmann W, Beck G, Bergmann A, Kesseler K. (1991) Synthesis and biological activity of new HMG-CoA reductase inhibitors. 3. Lactones of 6-phenoxy-3,5-dihydroxyhexanoic acids. J. Med. Chem., 34 (10): 2962-83. [PMID:1656041]

30. Karanewsky DS, Badia MC, Ciosek CP, Robl JA, Sofia MJ, Simpkins LM, DeLange B, Harrity TW, Biller SA, Gordon EM. (1990) Phosphorus-containing inhibitors of HMG-CoA reductase. 1. 4-[(2-arylethyl)hydroxyphosphinyl]-3-hydroxy-butanoic acids: a new class of cell-selective inhibitors of cholesterol biosynthesis. J. Med. Chem., 33 (11): 2952-6. [PMID:2231594]

31. Kawachi T, Rudney H. (1970) Solubilization and purification of beta-hydroxy-beta-methylglutaryl coenzyme A reductase from rat liver. Biochemistry, 9 (8): 1700-5. [PMID:4985697]

32. Lindgren V, Luskey KL, Russell DW, Francke U. (1985) Human genes involved in cholesterol metabolism: chromosomal mapping of the loci for the low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl-coenzyme A reductase with cDNA probes. Proc. Natl. Acad. Sci. U.S.A., 82 (24): 8567-71. [PMID:3866240]

33. McTaggart F, Buckett L, Davidson R, Holdgate G, McCormick A, Schneck D, Smith G, Warwick M. (2001) Preclinical and clinical pharmacology of Rosuvastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. Am. J. Cardiol., 87 (5A): 28B-32B. [PMID:11256847]

34. Ness GC, Eales SJ, Pendleton LC, Smith M. (1985) Activation of rat liver microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase by NADPH. Effects of dietary treatments. J. Biol. Chem., 260 (23): 12391-3. [PMID:3850089]

35. Pak VV, Koo M, Kwon DY, Shakhidoyatov KM, Yun L. (2010) Peptide fragmentation as an approach in modeling of an active peptide and designing a competitive inhibitory peptide for HMG-CoA reductase. Bioorg. Med. Chem., 18 (12): 4300-9. [PMID:20494585]

36. Pallottini V, Martini C, Bassi AM, Romano P, Nanni G, Trentalance A. (2006) Rat HMGCoA reductase activation in thioacetamide-induced liver injury is related to an increased reactive oxygen species content. J. Hepatol., 44 (2): 368-74. [PMID:16140414]

37. Park WK, Kennedy RM, Larsen SD, Miller S, Roth BD, Song Y, Steinbaugh BA, Sun K, Tait BD, Kowala MC et al.. (2008) Hepatoselectivity of statins: design and synthesis of 4-sulfamoyl pyrroles as HMG-CoA reductase inhibitors. Bioorg. Med. Chem. Lett., 18 (3): 1151-6. [PMID:18155906]

38. Patel DV, Gordon EM. (1991) C-2 desmethyl seco-mevinic acids. Monocyclic HMG-CoA reductase inhibitors. Bioorganic & Medicinal Chemistry Letters, 1 (10): 509-512.

39. Patil AD, ChanJA, Lois-Flamberg P, Mayer RJ, Westley JW. (1989) Novel Acetylenic Acids from the Root Bark of Paramacrolobium caeruleum: Inhibitors of 3-Hydroxy-3-methyl-glutaryl Coenzyme A Reductase. J. Nat. Prod., 52: 153-161.

40. Pfefferkorn JA, Choi C, Larsen SD, Auerbach B, Hutchings R, Park W, Askew V, Dillon L, Hanselman JC, Lin Z et al.. (2008) Substituted pyrazoles as hepatoselective HMG-CoA reductase inhibitors: discovery of (3R,5R)-7-[2-(4-fluoro-phenyl)-4-isopropyl-5-(4-methyl-benzylcarbamoyl)-2H-pyrazol-3-yl]-3,5-dihydroxyheptanoic acid (PF-3052334) as a candidate for the treatment of hypercholesterolemia. J. Med. Chem., 51 (1): 31-45. [PMID:18072721]

41. Pfefferkorn JA, Choi C, Song Y, Trivedi BK, Larsen SD, Askew V, Dillon L, Hanselman JC, Lin Z, Lu G et al.. (2007) Design and synthesis of novel, conformationally restricted HMG-CoA reductase inhibitors. Bioorg. Med. Chem. Lett., 17 (16): 4531-7. [PMID:17574411]

42. Pfefferkorn JA, Song Y, Sun KL, Miller SR, Trivedi BK, Choi C, Sorenson RJ, Bratton LD, Unangst PC, Larsen SD et al.. (2007) Design and synthesis of hepatoselective, pyrrole-based HMG-CoA reductase inhibitors. Bioorg. Med. Chem. Lett., 17 (16): 4538-44. [PMID:17574412]

43. Polo M, de Bravo MG, Carbone C. (1999) 3-Hydroxy-3-methylglutaryl coenzyme a reductase activity in liver of athymic mice with or without an implanted human carcinoma. Comp. Biochem. Physiol. B, Biochem. Mol. Biol., 122 (4): 433-7. [PMID:10392455]

44. Procopiou PA, Draper CD, Hutson JL, Inglis GG, Ross BC, Watson NS. (1993) Inhibitors of cholesterol biosynthesis. 2. 3,5-Dihydroxy-7-(N-pyrrolyl)-6-heptenoates, a novel series of HMG-CoA reductase inhibitors. J. Med. Chem., 36 (23): 3658-62. [PMID:8246234]

45. Robl JA, Duncan LA, Pluscec J, Karanewsky DS, Gordon EM, Ciosek CP, Rich LC, Dehmel VC, Slusarchyk DA, Harrity TW. (1991) Phosphorus-containing inhibitors of HMG-CoA reductase. 2. Synthesis and biological activities of a series of substituted pyridines containing a hydroxyphosphinyl moiety. J. Med. Chem., 34 (9): 2804-15. [PMID:1895299]

46. Roth BD, Blankley CJ, Chucholowski AW, Ferguson E, Hoefle ML, Ortwine DF, Newton RS, Sekerke CS, Sliskovic DR, Stratton CD. (1991) Inhibitors of cholesterol biosynthesis. 3. Tetrahydro-4-hydroxy-6-[2-(1H-pyrrol-1-yl)ethyl]-2H-pyran-2-one inhibitors of HMG-CoA reductase. 2. Effects of introducing substituents at positions three and four of the pyrrole nucleus. J. Med. Chem., 34 (1): 357-66. [PMID:1992137]

47. Roth BD, Bocan TM, Blankley CJ, Chucholowski AW, Creger PL, Creswell MW, Ferguson E, Newton RS, O'Brien P, Picard JA. (1991) Relationship between tissue selectivity and lipophilicity for inhibitors of HMG-CoA reductase. J. Med. Chem., 34 (1): 463-6. [PMID:1992149]

48. Sarver RW, Bills E, Bolton G, Bratton LD, Caspers NL, Dunbar JB, Harris MS, Hutchings RH, Kennedy RM, Larsen SD et al.. (2008) Thermodynamic and structure guided design of statin based inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase. J. Med. Chem., 51 (13): 3804-13. [PMID:18540668]

49. Schiefelbein D, Goren I, Fisslthaler B, Schmidt H, Geisslinger G, Pfeilschifter J, Frank S. (2008) Biphasic regulation of HMG-CoA reductase expression and activity during wound healing and its functional role in the control of keratinocyte angiogenic and proliferative responses. J. Biol. Chem., 283 (22): 15479-90. [PMID:18390541]

50. Sit SY, Parker RA, Motoc I, Han W, Balasubramanian N, Catt JD, Brown PJ, Harte WE, Thompson MD, Wright JJ. (1990) Synthesis, biological profile, and quantitative structure-activity relationship of a series of novel 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. J. Med. Chem., 33 (11): 2982-99. [PMID:2231596]

51. Sliskovic DR, Blankley CJ, Krause BR, Newton RS, Picard JA, Roark WH, Roth BD, Sekerke C, Shaw MK, Stanfield RL. (1992) Inhibitors of cholesterol biosynthesis. 6. trans-6-[2-(2-N-heteroaryl-3,5-disubstituted- pyrazol-4-yl)ethyl/ethenyl]tetrahydro-4-hydroxy-2H-pyran-2-ones. J. Med. Chem., 35 (11): 2095-103. [PMID:1597859]

52. Sliskovic DR, Picard JA, Roark WH, Roth BD, Ferguson E, Krause BR, Newton RS, Sekerke C, Shaw MK. (1991) Inhibitors of cholesterol biosynthesis. 4. trans-6-[2-(substituted-quinolinyl)ethenyl/ethyl]tetrahydro-4-hydroxy-2 H-pyran-2-ones, a novel series of HMG-CoA reductase inhibitors. J. Med. Chem., 34 (1): 367-73. [PMID:1992138]

53. Sliskovic DR, Roth BD, Wilson MW, Hoefle ML, Newton RS. (1990) Inhibitors of cholesterol biosynthesis. 2. 1,3,5-trisubstituted [2-(tetrahydro-4-hydroxy-2-oxopyran-6-yl)ethyl]pyrazoles. J. Med. Chem., 33 (1): 31-8. [PMID:2296027]

54. Stokker GE, Alberts AW, Gilfillan JL, Huff JW, Smith RL. (1986) 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. 5. 6-(Fluoren-9-yl)- and 6-(fluoren-9-ylidenyl)-3,5-dihydroxyhexanoic acids and their lactone derivatives. J. Med. Chem., 29 (5): 852-5. [PMID:3701793]

55. Stokker GE, Hoffman WF, Alberts AW, Cragoe EJ, Deana AA, Gilfillan JL, Huff JW, Novello FC, Prugh JD, Smith RL. (1985) 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. 1. Structural modification of 5-substituted 3,5-dihydroxypentanoic acids and their lactone derivatives. J. Med. Chem., 28 (3): 347-58. [PMID:3973903]

56. Suzuki M, Iwasaki H, Fujikawa Y, Sakashita M, Kitahara M, Sakoda R. (2001) Synthesis and biological evaluations of condensed pyridine and condensed pyrimidine-based HMG-CoA reductase inhibitors. Bioorg. Med. Chem. Lett., 11 (10): 1285-8. [PMID:11392538]

57. Thilagavathi R, Kumar R, Aparna V, Sobhia ME, Gopalakrishnan B, Chakraborti AK. (2005) Three-dimensional quantitative structure (3-D QSAR) activity relationship studies on imidazolyl and N-pyrrolyl heptenoates as 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) inhibitors by comparative molecular similarity indices analysis (CoMSIA). Bioorg. Med. Chem. Lett., 15 (4): 1027-32. [PMID:15686906]

58. Wess G, Kramer W, Han XB, Bock K, Enhsen A, Glombik H, Baringhaus KH, Böger G, Urmann M, Hoffmann A. (1994) Synthesis and biological activity of bile acid-derived HMG-CoA reductase inhibitors. The role of 21-methyl in recognition of HMG-CoA reductase and the ileal bile acid transport system. J. Med. Chem., 37 (20): 3240-6. [PMID:7932551]

59. Wysocka-Kapcinska M, Lutyk-Nadolska J, Kiliszek M, Plochocka D, Maciag M, Leszczynska A, Rytka J, Burzynska B. (2009) Functional expression of human HMG-CoA reductase in Saccharomyces cerevisiae: a system to analyse normal and mutated versions of the enzyme in the context of statin treatment. J. Appl. Microbiol., 106 (3): 895-902. [PMID:19187128]

60. Yasojima K, McGeer EG, McGeer PL. (2001) 3-hydroxy-3-methylglutaryl-coenzyme A reductase mRNA in Alzheimer and control brain. Neuroreport, 12 (13): 2935-8. [PMID:11588606]

61. Young NL, Saudek CD, Crawford SA, Zuckerbrod SL. (1982) Recovery and activation of hydroxymethylglutaryl coenzyme A reductase from rat small intestine. J. Lipid Res., 23 (2): 257-65. [PMID:7077140]

62. Yuan ZB, Han TQ, Jiang ZY, Fei J, Zhang Y, Qin J, Tian ZJ, Shang J, Jiang ZH, Cai XX et al.. (2005) Expression profiling suggests a regulatory role of gallbladder in lipid homeostasis. World J. Gastroenterol., 11 (14): 2109-16. [PMID:15810076]

63. Zhao S, Zhou W, Liu J. (2009) Synthesis and HMG-CoA reductase inhibition of 2-cyclopropyl-4-thiophenyl-quinoline mevalonolactones. Bioorg. Med. Chem., 17 (23): 7915-23. [PMID:19879766]

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Helen E. Benson.
Lanosterol biosynthesis pathway: hydroxymethylglutaryl-CoA reductase. Last modified on 04/04/2016. Accessed on 19/08/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=639.