hydroxymethylglutaryl-CoA reductase

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Lanosterol biosynthesis pathway
hydroxymethylglutaryl-CoA reductase

Target not currently curated in GtoImmuPdb

Target id: 639

Nomenclature: hydroxymethylglutaryl-CoA reductase

Family: Lanosterol biosynthesis pathway

Gene and Protein Information
Species	TM	AA	Chromosomal Location	Gene Symbol	Gene Name	Reference
Human	7	888	5q13.3	HMGCR	3-hydroxy-3-methylglutaryl-CoA reductase	32
Mouse	7	887	13 50.65 cM	Hmgcr	3-hydroxy-3-methylglutaryl-Coenzyme A reductase
Rat	7	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
Alphafold	P04035 (Hs), Q01237 (Mm), P51639 (Rn)
BRENDA	1.1.1.34
CATH/Gene3D	3.30.70.420, 3.90.770.10, 1.10.3270.10
ChEMBL Target	CHEMBL402 (Hs), CHEMBL2764 (Mm), CHEMBL3247 (Rn)
DrugBank Target	P04035 (Hs)
Ensembl Gene	ENSG00000113161 (Hs), ENSMUSG00000021670 (Mm), ENSRNOG00000016122 (Rn)
Entrez Gene	3156 (Hs), 15357 (Mm), 25675 (Rn)
Human Protein Atlas	ENSG00000113161 (Hs)
KEGG Enzyme	1.1.1.34
KEGG Gene	hsa:3156 (Hs), mmu:15357 (Mm), rno:25675 (Rn)
OMIM	142910 (Hs)
Pharos	P04035 (Hs)
RefSeq Nucleotide	NM_001130996 (Hs), NM_000859 (Hs), NM_008255 (Mm), NM_013134 (Rn)
RefSeq Protein	NP_001124468 (Hs), NP_000850 (Hs), NP_032281 (Mm), NP_037266 (Rn)
UniProtKB	P04035 (Hs), Q01237 (Mm), P51639 (Rn)
Wikipedia	HMGCR (Hs)

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	K_m	4x10^-6	M	pK_m	5.4	Intestinal enzyme, in vitro assay	pH 7.5. 37ºC		61
(S)-3-hydroxy-3-methylglutaryl-CoA	Rn	K_m	6x10^-6	M	pK_m	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	K_m	1.2x10^-5	M	pK_m	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	K_m	1.43x10^-5	M	pK_m	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	K_m	2.42x10^-5	M	pK_m	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	K_m	7x10^-5	M	pK_m	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	K_m	2.1x10^-5	M	pK_m	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	V_max	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	V_max	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	V_max	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	V_max	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	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

Key to terms and symbols

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Ligand		Sp.	Action	Value	Parameter	Reference
o-hydroxyatorvastatin		Rn	Inhibition	7.6	pK_d	48
⤷	pK_d 7.6 (K_d 2.74x10^-8 M) [48]
lovastatin		Hs	Competitive	9.2	pK_i	2
⤷	pK_i 9.2 (K_i 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	pK_i	16,21
⤷	pK_i 9.0 (K_i 1x10^-9 M) [16] Description: in vitro inhibition of HMG-CoA reductase Conditions: Assay used the acid form of mevastatin pK_i 8.9 (K_i 1.4x10^-9 M) [21] Conditions: Substrate concentrations: 20µM HMG CoA, 2.1 mM NADP
rosuvastatin		Hs	Competitive	8.6	pK_i	10
⤷	pK_i 8.6 (K_i 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	pK_i	14
⤷	pK_i 8.5 (K_i 3x10^-9 M) [14]
cerivastatin		Hs	Competitive	8.2	pK_i	10
⤷	pK_i 8.2 (K_i 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	pK_i	10
⤷	pK_i 7.8 (K_i 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	pK_i	14
⤷	pK_i 7.8 (K_i 1.6x10^-8 M) [14]
DFGYVAE		Hs	Competitive	7.3	pK_i	35
⤷	pK_i 7.3 (K_i 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	pK_i	10,23
⤷	pK_i 7.6 (K_i 2.8x10^-8 M) [23] pK_i 6.6 (K_i 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	pK_i	10
⤷	pK_i 7.0 (K_i 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	pK_i	63
⤷	pK_i 5.1 (K_i 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, 37^oC 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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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 USA, 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. DOI: 10.1016/S0960-894X(00)80665-4

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. DOI: 10.1016/S0960-894X(01)81069-6

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. Bioorg Med Chem Lett, 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. DOI: 10.1016/S0960-894X(01)80788-5

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]

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