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squalene synthase

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Target not currently curated in GtoImmuPdb

Target id: 645

Nomenclature: squalene synthase

Family: Lanosterol biosynthesis pathway

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 2 417 8p23.1 FDFT1 farnesyl-diphosphate farnesyltransferase 1 30
Mouse 2 416 14 33.24 cM Fdft1 farnesyl diphosphate farnesyl transferase 1
Rat 2 416 15p12 Fdft1 farnesyl diphosphate farnesyl transferase 1
Previous and Unofficial Names Click here for help
farnesyltransferase | FDFT1 | presqualene synthase | presqualene-diphosphate synthase | SQS | squalene synthetase | SSase | FPP:FPP farnesyltransferase
Database Links Click here for help
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KEGG Gene
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RefSeq Protein
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Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the human squalene synthase
PDB Id:  3VJ8
Resolution:  1.52Å
Species:  Human
References:  21
Image of receptor 3D structure from RCSB PDB
Description:  Human squalene synthase in complex with 2-(1-{2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl}-4-piperidinyl)acetic acid
PDB Id:  3V66
Ligand:  compound 15a [PMID: 22464687]
Resolution:  1.8Å
Species:  Human
References:  14
Enzyme Reaction Click here for help
EC Number: 2.5.1.21 2trans,trans-farnesyl diphosphate -> presqualene diphosphate + diphosphate
presqualene diphosphate + NAD(P)H + H+ -> squalene + diphosphate + NAD(P)+
Substrates and Reaction Kinetics Click here for help
Substrate Sp. Property Value Units Standard property Standard value Assay description Assay conditions Comments Reference
NADPH Substrate is endogenous in the given species Rn Km 4x10-5 M pKm 4.4 in vitro assay pH 7.4, 37ºC Concentration of substrates: 2.0mM NADPH, 10µM FPP, 5.0mM MgCl2 in a total volume of 100µl 35
trans,trans-farnesyl diphosphate Substrate is endogenous in the given species Rn Km 1x10-6 M pKm 6.0 in vitro assay pH 7.4, 37ºC Concentration of substrates: 2.0mM NADPH, 10µM FPP, 5.0mM MgCl2 in a total volume of 100µl 35
trans,trans-farnesyl diphosphate Substrate is endogenous in the given species Rn Km 1.8x10-6 M pKm 5.7 recombinant enzyme expressed in E coli, isolated, in vitro assay pH 7.5 Concentration of FPP: 0.4-10µM 40
trans,trans-farnesyl diphosphate Substrate is endogenous in the given species Hs Km 2.3x10-6 M pKm 5.6 recombinant enzyme expressed in E coli, isolated, in vitro assay pH 7.5 Concentration of FPP: 0.4-10µM 40
NADH Substrate is endogenous in the given species Rn Km 8x10-4 M pKm 3.1 in vitro assay pH 7.4, 37ºC Concentration of substrates: 2.0mM NADPH, 10µM FPP, 5.0mM MgCl2 in a total volume of 100µl 35
trans,trans-farnesyl diphosphate Substrate is endogenous in the given species Rn Vmax 1.2 µmol/min/mg in vitro assay pH 7.4, 37ºC Concentration of substrates: 2.0mM NADPH, 10µM FPP, 5.0mM MgCl2 in a total volume of 100µl 35
Cofactors Click here for help
Cofactor Species Comments Reference
Mg2+ Human 32
NADPH Human 32
NADH Human 32

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
zaragozic acid B Small molecule or natural product Rn Inhibition 10.5 pKi 1
pKi 10.5 (Ki 2.9x10-11 M) [1]
Conditions: Concentration of substrates: 0.2-10µM FPP, 10mM NADPH. pH 7.5, 30°C
zaragozic acid C Small molecule or natural product Rn Inhibition 10.4 pKi 1,10
pKi 10.4 (Ki 4.5x10-11 M) [1,10]
Description: Inhibition of rat squalene synthase
Conditions: Concentration of substrates: 0.2-10µM FPP, 10mM NADPH. pH 7.5, 30°C (8419946)
zaragozic acid A Small molecule or natural product Ligand has a PDB structure Rn Inhibition 10.1 pKi 1
pKi 10.1 (Ki 7.8x10-11 M) [1]
Description: Compound was tested for inhibition of squalene synthase in rat liver.
Conditions: Concentration of substrates: 0.2-10µM FPP, 10mM NADPH. pH 7.5, 30°C
zaragozic acid A Small molecule or natural product Ligand has a PDB structure Hs Inhibition 9.6 pKi 37
pKi 9.6 (Ki 2.5x10-10 M) [37]
Description: Human enzyme expressed in yeast, in vitro assay
Conditions: pH 7.4, 37°C
compound 1e [Brown et al., 1997] Small molecule or natural product Rn Inhibition 8.7 pKi 7
pKi 8.7 (Ki 2x10-9 M) [7]
Description: Tested for its inhibitory activity against rat microsomal quinuclidine squalene synthase (SQS)
compound 6 [Biller et al., 1991] Small molecule or natural product Rn Inhibition 7.4 pKi 3
pKi 7.4 (Ki 3.7x10-8 M) [3]
Description: Tested for inhibitory potency against rat liver microsomal squalene synthase
compound 1c [Brown et al., 1997] Small molecule or natural product Hs Inhibition 7.4 pKi 7
pKi 7.4 (Ki 4.3x10-8 M) [7]
Description: Tested for its inhibitory activity against human microsomal quinuclidine squalene synthase (SQS)
compound 15 [PMID: 19456099] Small molecule or natural product Hs Inhibition 6.5 pKi 39
pKi 6.5 (Ki 3x10-7 M) [39]
Description: Inhibition of human recombinant squalene synthase expressed in Escherichia coli cells assessed as conversion of [3H]FPP to squalene by liquid scintillation
Conditions: Substrate concentrations: 0.25mM NADPH, 0.1nmol FPP in a volume of 200µL. pH 7.4, 37°C
BPH-830 Small molecule or natural product Hs Inhibition 6.3 pKi 39
pKi 6.3 (Ki 5.3x10-7 M) [39]
Description: Inhibition of human recombinant squalene synthase expressed in Escherichia coli cells assessed as conversion of [3H]FPP to squalene by liquid scintillation
Conditions: Substrate concentrations: 0.25mM NADPH, 0.1nmol FPP in a volume of 200µL. pH 7.4, 37°C
compound 13 [PMID: 19456099] Small molecule or natural product Hs Inhibition 6.3 pKi 39
pKi 6.3 (Ki 5.2x10-7 M) [39]
Description: Inhibition of human recombinant squalene synthase expressed in Escherichia coli cells assessed as conversion of [3H]FPP to squalene by liquid scintillation
Conditions: Substrate concentrations: 0.25mM NADPH, 0.1nmol FPP in a volume of 200µL. pH 7.4, 37°C
SQ-109 Small molecule or natural product Guide to Malaria Pharmacology Ligand Hs Inhibition 6.1 pKi 20
pKi 6.1 (Ki 7.4x10-7 M) [20]
compound 21 [PMID: 7473541] Small molecule or natural product Ligand has a PDB structure Rn Inhibition 11.4 pIC50 5
pIC50 11.4 [5]
Description: Inhibition of rat microsomal squalene synthase
Conditions: Concentration of substrates: 20µM FPP, 0.9 mM NADPH. 37°C
compound 5d [PMID: 7966163] Small molecule or natural product Rn Inhibition 10.4 pIC50 27
pIC50 10.4 (IC50 4x10-11 M) [27]
Description: Tested for inhibition against squalene synthase enzyme in rat liver
Conditions: Substrate concentration: 5µM FPP
compound 5d [PMID: 7966163] Small molecule or natural product Rn Inhibition 10.4 pIC50 27
pIC50 10.4 (IC50 4x10-11 M) [27]
Description: Tested for inhibition against squalene synthase enzyme in rat liver
Conditions: Substrate concentration: 5µM FPP
compound 19 [PMID: 7473541] Small molecule or natural product Rn Inhibition 10.3 pIC50 5
pIC50 10.3 (IC50 5x10-11 M) [5]
Description: Inhibition of rat microsomal squalene synthase
Conditions: Concentration of substrates: 20µM FPP, 0.9 mM NADPH. 37°C
compound 6g [PMID: 7966163] Small molecule or natural product Rn Inhibition 10.2 pIC50 27
pIC50 10.2 (IC50 6x10-11 M) [27]
Description: Tested for inhibition against squalene synthase enzyme in rat liver
Conditions: Substrate concentration: 5µM FPP
compound 4e [PMID: 7966163] Small molecule or natural product Rn Inhibition 10.1 pIC50 27
pIC50 10.1 (IC50 7x10-11 M) [27]
Description: Tested for inhibition against squalene synthase enzyme in rat liver
Conditions: Substrate concentration: 5µM FPP
compound 6d [PMID: 7966163] Small molecule or natural product Rn Inhibition 10.1 pIC50 27
pIC50 10.1 (IC50 9x10-11 M) [27]
Description: Tested for inhibition against squalene synthase enzyme in rat liver
Conditions: Substrate concentration: 5µM FPP
compound 6c [PMID: 7966163] Small molecule or natural product Rn Inhibition 9.9 pIC50 27
pIC50 9.9 (IC50 1.2x10-10 M) [27]
Description: Tested for inhibition against squalene synthase enzyme in rat liver
Conditions: Substrate concentration: 5µM FPP
compound 3f [PMID: 7966163] Small molecule or natural product Rn Inhibition 9.9 pIC50 27
pIC50 9.9 (IC50 1.3x10-10 M) [27]
Description: Tested for inhibition against squalene synthase enzyme in rat liver
Conditions: Substrate concentration: 5µM FPP
L-735021 Small molecule or natural product Rn Inhibition 9.9 pIC50 27
pIC50 9.9 (IC50 1.4x10-10 M) [27]
Description: Tested for inhibition against squalene synthase enzyme in rat liver
Conditions: Substrate concentration: 5µM FPP
compound 28 [PMID: 7473541] Small molecule or natural product Rn Inhibition 9.7 pIC50 5
pIC50 9.7 (IC50 2x10-10 M) [5]
Description: Inhibition of rat microsomal squalene synthase
Conditions: Concentration of substrates: 20µM FPP, 0.9 mM NADPH. 37°C
compound 20 [PMID: 7473541] Small molecule or natural product Rn Inhibition 9.2 pIC50 5
pIC50 9.2 (IC50 6x10-10 M) [5]
Description: Inhibition of rat microsomal squalene synthase
Conditions: Concentration of substrates: 20µM FPP, 0.9 mM NADPH. 37°C
J-104118 Small molecule or natural product Hs Inhibition 9.1 – 9.3 pIC50 16
pIC50 9.3 (IC50 5.2x10-10 M) [16]
Description: Inhibitory activity against HepG2 Squalene Synthase (SQS)
pIC50 9.1 (IC50 7.3x10-10 M) [16]
Description: Inhibitory activity against HepG2 Squalene Synthase (SQS)
zaragozic acid A Small molecule or natural product Ligand has a PDB structure Hs Inhibition 9.1 pIC50 40
pIC50 9.1 (7x10-10 M) [40]
Description: in vitro, soluable microsomal enzymes purified from rat and human liver microsomes
Conditions: Concentration of FPP: 20µM
compound 6 [PMID: 7629799] Small molecule or natural product Rn Inhibition 9.1 pIC50 23-24
pIC50 9.1 (IC50 7x10-10 M) [24]
Description: Inhibition rat liver microsomal squalene synthase. In vivo assay
pIC50 9.1 (IC50 7x10-10 M) [23]
Description: Inhibitory activity against rat liver microsomal squalene synthase was determined using [3H]-FPP as radioligand
compound 6 [PMID: 7629799] Small molecule or natural product Hs Inhibition 9.0 pIC50 38
pIC50 9.0 (IC50 1x10-9 M) [38]
Description: Inhibition of human recombinant squalene synthase expressed in Escherichia coli BL21 (DE3) cells assessed as formation of 1,10-dioic acid metabolite by liquid scintillation
Conditions: Substrate concentrations: 0.25mM NADPH, 0.1nmol FPP in a volume of 200µL. pH 7.4, 37°C
SQ-34919 Small molecule or natural product Rn Inhibition 9.0 pIC50 23-24
pIC50 9.0 (IC50 1x10-9 M) [24]
Description: Inhibition rat liver microsomal squalene synthase
pIC50 9.0 (IC50 1x10-9 M) [23]
Description: Inhibitory activity against rat liver microsomal squalene synthase was determined using [3H]-FPP as radioligand
Conditions: compound is a tetrasodium salt
compound 15a [PMID: 22464687] Small molecule or natural product Ligand has a PDB structure Hs Inhibition 8.9 pIC50 14
pIC50 8.9 (IC50 1.3x10-9 M) [14]
E5700 Small molecule or natural product Hs Inhibition 8.8 pIC50 31
pIC50 8.8 (IC50 1.5x10-9 M) [31]
Description: Inhibition of human recombinant squalene synthase
Conditions: Substrate concentration: 0.5µM FPP. pH 7.4, 37°C
compound 32 [PMID: 19191557] Small molecule or natural product Hs Inhibition 8.7 pIC50 38
pIC50 8.7 (IC50 2x10-9 M) [38]
Description: Inhibition of human recombinant squalene synthase expressed in Escherichia coli BL21 (DE3) cells assessed as formation of 1,10-dioic acid metabolite by liquid scintillation
Conditions: Substrate concentrations: 0.25mM NADPH, 0.1nmol FPP in a volume of 200µL. pH 7.4, 37°C
compound 2e [PMID: 7629799] Small molecule or natural product Rn Inhibition 8.6 pIC50 24
pIC50 8.6 (IC50 2.5x10-9 M) [24]
Description: Inhibition rat liver microsomal squalene synthase
J-104123 Small molecule or natural product Hs Inhibition 8.6 pIC50 17
pIC50 8.6 (IC50 2.5x10-9 M) [17]
Description: Inhibitory activity against squalene synthase (SQS) obtained from HepG2 cells
compound 2d [PMID: 7629799] Small molecule or natural product Rn Inhibition 8.6 pIC50 24
pIC50 8.6 (IC50 2.6x10-9 M) [24]
Description: Inhibition rat liver microsomal squalene synthase
compound 23 [PMID: 8709131] Small molecule or natural product Rn Inhibition 8.5 pIC50 6
pIC50 8.5 (IC50 3x10-9 M) [6]
Description: In vitro inhibition against rat microsomal squalene synthase (SS)
Conditions: Concentration of substrates: 20µM FPP, 0.9 mM NADPH. 37°C
compound 3 [PMID: 19191557] Small molecule or natural product Hs Inhibition 8.5 pIC50 38
pIC50 8.5 (IC50 3x10-9 M) [38]
Description: Inhibition of human recombinant squalene synthase expressed in Escherichia coli BL21 (DE3) cells assessed as formation of 1,10-dioic acid metabolite by liquid scintillation
Conditions: Substrate concentrations: 0.25mM NADPH, 0.1nmol FPP in a volume of 200µL. pH 7.4, 37°C
compound 8 [PMID: 19191557] Small molecule or natural product Hs Inhibition 8.5 pIC50 38
pIC50 8.5 (IC50 3x10-9 M) [38]
Description: Inhibition of human recombinant squalene synthase expressed in Escherichia coli BL21 (DE3) cells assessed as formation of 1,10-dioic acid metabolite by liquid scintillation
Conditions: Substrate concentrations: 0.25mM NADPH, 0.1nmol FPP in a volume of 200µL. pH 7.4, 37°C
compound 15 [PMID: 8709131] Small molecule or natural product Rn Inhibition 8.4 pIC50 6
pIC50 8.4 (IC50 4x10-9 M) [6]
Description: In vitro inhibition against rat microsomal squalene synthase (SS)
Conditions: Concentration of substrates: 20µM FPP, 0.9 mM NADPH. 37°C
compound 7 [PMID: 8496919] Small molecule or natural product Rn Inhibition 8.4 pIC50 29
pIC50 8.4 (IC50 4x10-9 M) [29]
Description: Tested for inhibitory activity against squalene synthetase in the presence of inorganic pyrophosphate (PPi)
Conditions: Concentration of substrate: 10mM FPP. pH 7.4, 37°C
compound 35 [PMID: 19191557] Small molecule or natural product Hs Inhibition 8.4 pIC50 38
pIC50 8.4 (IC50 4x10-9 M) [38]
Description: Inhibition of human recombinant squalene synthase expressed in Escherichia coli BL21 (DE3) cells assessed as formation of 1,10-dioic acid metabolite by liquid scintillation
Conditions: Substrate concentrations: 0.25mM NADPH, 0.1nmol FPP in a volume of 200µL. pH 7.4, 37°C
compound 17 [PMID: 8709131] Small molecule or natural product Rn Inhibition 8.3 pIC50 6
pIC50 8.3 (IC50 5x10-9 M) [6]
Description: In vitro inhibition against rat microsomal squalene synthase (SS)
Conditions: Concentration of substrates: 20µM FPP, 0.9 mM NADPH. 37°C
compound 21 [PMID: 19191557] Small molecule or natural product Hs Inhibition 8.3 pIC50 38
pIC50 8.3 (IC50 5x10-9 M) [38]
Description: Inhibition of human recombinant squalene synthase expressed in Escherichia coli BL21 (DE3) cells assessed as formation of 1,10-dioic acid metabolite by liquid scintillation
Conditions: Substrate concentrations: 0.25mM NADPH, 0.1nmol FPP in a volume of 200µL. pH 7.4, 37°C
compound 2a (+) [PMID: 8709131] Small molecule or natural product Rn Inhibition 8.1 pIC50 6
pIC50 8.1 (IC50 7x10-9 M) [6]
Description: In vitro inhibition against rat microsomal squalene synthase (SS)
Conditions: Concentration of substrates: 20µM FPP, 0.9 mM NADPH. 37°C
compound 8 [Brinkman et al., 1996] Small molecule or natural product Rn Inhibition 8.1 pIC50 4
pIC50 8.1 (IC50 9x10-9 M) [4]
Description: Compound was tested for inhibitory activity against squalene synthase using rat liver microsomal assay
Conditions: Substrate concentration: 10µM FPP. pH 7.4, 37°C
compound 7 [Brinkman et al., 1996] Small molecule or natural product Rn Inhibition 8.1 pIC50 4
pIC50 8.1 (IC50 9x10-9 M) [4]
Description: Compound was tested for inhibitory activity against squalene synthase using rat liver microsomal assay
Conditions: Substrate concentration: 10µM FPP. pH 7.4, 37°C
compound 4 [Brinkman et al., 1996] Small molecule or natural product Rn Inhibition 8.0 pIC50 4
pIC50 8.0 (IC50 1x10-8 M) [4]
Description: Compound was tested for inhibitory activity against squalene synthase using rat liver microsomal assay
Conditions: Substrate concentration: 10µM FPP. pH 7.4, 37°C
compound 4 [PMID: 8709131] Small molecule or natural product Rn Inhibition 8.0 pIC50 6
pIC50 8.0 (IC50 1.1x10-8 M) [6]
Description: In vitro inhibition against rat microsomal squalene synthase (SS)
Conditions: Concentration of substrates: 20µM FPP, 0.9 mM NADPH. 37°C
compound 16a [Sharratt et al., 1994] Small molecule or natural product Rn Inhibition 8.0 pIC50 33
pIC50 8.0 (IC50 1.1x10-8 M) [33]
Description: In vitro inhibitory concentration against squalene synthase from male rat liver microsomes
compound 5j [PMID: 9216829] Small molecule or natural product Rn Inhibition 7.9 pIC50 11
pIC50 7.9 (IC50 1.3x10-8 M) [11]
Description: In vitro inhibitory activity against Squalene Synthase. Enzyme from rat liver microsomes.
compound 5m [PMID: 9216829] Small molecule or natural product Rn Inhibition 7.8 pIC50 11
pIC50 7.8 (IC50 1.4x10-8 M) [11]
Description: In vitro inhibitory activity against Squalene Synthase
compound 3a [PMID: 12238936] Small molecule or natural product Hs Inhibition 7.8 pIC50 25
pIC50 7.8 (IC50 1.5x10-8 M) [25]
Description: Inhibition of squalene synthase from human hepatoma cells (HepG2). *this value also obtained for rat liver enzyme for this compound
Conditions: Substrate concentrations: 5µM FPP, 1mM NADPH. pH 7.4, 37°C
compound 3f [PMID: 12238936] Small molecule or natural product Hs Inhibition 7.8 pIC50 25
pIC50 7.8 (IC50 1.5x10-8 M) [25]
Description: Inhibition of squalene synthase from human hepatoma cells (HepG2)
Conditions: Substrate concentrations: 5µM FPP, 1mM NADPH. pH 7.4, 37°C
compound 4 [PMID: 8576905] Small molecule or natural product Rn Inhibition 7.8 pIC50 23
pIC50 7.8 (IC50 1.5x10-8 M) [23]
Description: Inhibitory activity against rat liver microsomal squalene synthase was determined using [3H]-FPP as radioligand
compound 1 [Overhand et al., 1997] Small molecule or natural product Hs Inhibition 7.7 pIC50 26
pIC50 7.7 (IC50 1.8x10-8 M) [26]
Description: Inhibition of Squalene Synthase
NB-598 Small molecule or natural product Ligand has a PDB structure Hs Inhibition 7.7 pIC50 12
pIC50 7.7 (IC50 2x10-8 M) [12]
Description: In vitro ability to inhibit cholesterol biosynthesis in HepG2 cells in culture from [14C]-acetate
Conditions: IC50 calculated from % cholesterol inhibition
1-allyl-2-[3-(isopropylamino)propoxy]-9H-carbazole Small molecule or natural product Hs Inhibition 7.5 pIC50 15
pIC50 7.5 (IC50 3.2x10-8 M) [15]
Description: in vitro. Rat and human liver microsomes assayed using the Amin technique.
Conditions: Substrate concentrations: 5µM FPP, 1mM NADPH. pH 7.5, 30°C. IC50 values determined by a single experimental run in duplicate.
compound 4q [PMID: 7650673] Small molecule or natural product Hs Inhibition 7.2 pIC50 12
pIC50 7.2 (IC50 6x10-8 M) [12]
Description: In vitro ability to inhibit cholesterol biosynthesis in HepG2 cells in culture from [14C]-mevalonate.
Conditions: IC50 calculated from % cholesterol inhibition
YM-75440 Small molecule or natural product Hs Inhibition 7.2 pIC50 15
pIC50 7.2 (6.3x10-8 M) [15]
Description: in vitro . Rat and human liver microsomes assayed using the Amin techinique
Conditions: Substrate concentrations: 5µM FPP, 1mM NADPH. pH 7.5, 30°C. IC50 values determined by a single experimental run in duplicate
1-allyl-2-[3-(isopropylamino)propoxy]-9H-carbazole Small molecule or natural product Rn Inhibition 7.2 pIC50 15
pIC50 7.2 (IC50 6.6x10-8 M) [15]
Description: in vitro. Rat and human liver microsomes assayed using the Amin technique.
Conditions: Substrate concentrations: 5µM FPP, 1mM NADPH. pH 7.5, 30°C. IC50 values determined by a single experimental run in duplicate.
1-allyl-2-[3-(isopropylamino)propoxy]-9H-xanthen-9-one Small molecule or natural product Hs Inhibition 6.9 pIC50 15
pIC50 6.9 (IC50 1.2x10-7 M) [15]
Description: in vitro. Rat and human liver microsomes assayed using the Amin technique.
Conditions: Substrate concentrations: 5µM FPP, 1mM NADPH. pH 7.5, 30°C. IC50 values determined by a single experimental run in duplicate.
1-allyl-2-[3-(isopropylamino)propoxy]-9H-xanthen-9-one Small molecule or natural product Rn Inhibition 6.9 pIC50 15
pIC50 6.9 (IC50 1.2x10-7 M) [15]
Description: in vitro. Rat and human liver microsomes assayed using the Amin technique.
Conditions: Substrate concentrations: 5µM FPP, 1mM NADPH. pH 7.5, 30°C, IC50 values determined by a single experimental run in duplicate.
compound 15 [Biller et al., 1993] Small molecule or natural product Rn Inhibition 6.9 pIC50 2
pIC50 6.9 (IC50 1.25x10-7 M) [2]
Description: Tested for inhibitory potency against rat liver microsomal squalene synthase
CP-294838 Small molecule or natural product Rn Inhibition 6.9 pIC50 40
pIC50 6.9 (1.3x10-7 M) [40]
Description: in vitro, soluable microsomal enzymes purified from rat and human liver microsomes
Conditions: Concentration of FPP: 20µM
compound 12 [Wattanasin et al.,1997] Small molecule or natural product Rn Inhibition 6.6 – 6.8 pIC50 41
pIC50 6.8 (IC50 1.7x10-7 M) [41]
Description: The compound was tested for inhibition of purified rat hepatic squalene synthase in the presence of 1.2 mM NADPH and 1.0 mM inorganic pyrophosphate. In vitro assay.
pIC50 6.6 (IC50 2.3x10-7 M) [41]
Description: Inhibitory activity against squalene synthase using rat liver microsomal assay
compound 14 [PMID: 9871507] Small molecule or natural product Rn Inhibition 6.6 pIC50 36
pIC50 6.6 (IC50 2.4x10-7 M) [36]
Description: Compound was tested for inhibition of squalene synthase from rat liver microsomes using [3H]-Farnesyl pyrophosphate (FPP) as substrate
Conditions: pH 7.4
L-731120 Small molecule or natural product Rn Inhibition 6.6 pIC50 13
pIC50 6.6 (IC50 2.6x10-7 M) [13]
Description: In vitro inhibitory activity against rat squalene synthase
ibandronic acid Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Inhibition 6.2 pIC50 22
pIC50 6.2 (IC50 6.4x10-7 M) [22]
Description: Inhibition of squalene synthase in rat liver microsomes assessed as conversion of [1-3H]FPP to [3H]squalene level after 60 mins by liquid scintillation counting
Conditions: 0.02µCi FPP, 2mM NADPH. 30°C, assay performed in duplicate
compound 4g [PMID: 17709461] Small molecule or natural product Hs Inhibition 6.2 pIC50 8
pIC50 6.2 (IC50 6.6x10-7 M) [8]
Description: Inhibition of human recombinant squalene synthase expressed in Escherichia coli BL21(DE3 pLysS) by liquid scintillation counter
Conditions: Substrate concentration: 0.5µM FPP, 0.25mM NADPH. pH 7.4, 37°C
L-731128 Small molecule or natural product Rn Inhibition 6.1 pIC50 13
pIC50 6.1 (IC50 7.67x10-7 M) [13]
Description: In vitro inhibitory activity against rat squalene synthase
compound 1 [PMID: 8496942] Small molecule or natural product Rn Inhibition 5.2 – 7.0 pIC50 28
pIC50 7.0 (IC50 1x10-7 M) [28]
Description: Inhibitory activity against squalene synthetase in the presence of inorganic pyrophosphate in rat liver microsomal assay
pIC50 5.2 (IC50 6.9x10-6 M) [28]
Description: Inhibitory activity against squalene synthetase in rat liver microsomal assay
compound 9 [PMID: 18754614] Small molecule or natural product Rn Inhibition 6.0 pIC50 19
pIC50 6.0 (IC50 1x10-6 M) [19]
Description: Inhibition of squalene synthase in rat liver microsome measured by convertion of [3H]FPP to squalene
Conditions: Substrate concentrations: 0.5mM NADPH, 0.5µM FPP. pH 7.4, 37°C
compound 11 [PMID: 7473541] Small molecule or natural product Rn Inhibition 5.8 pIC50 5
pIC50 5.8 (IC50 1.4x10-6 M) [5]
Description: Inhibition of rat microsomal squalene synthase
Conditions: Concentration of substrates: 20µM FPP, 0.9 mM NADPH. 37°C
compound 17 [Shechter et al., 1996] Small molecule or natural product Rn Inhibition 5.7 pIC50 34
pIC50 5.7 (IC50 2x10-6 M) [34]
Description: Inhibitory activity against rat hepatic squalene synthase
compound 8 [PMID: 18754614] Small molecule or natural product Rn Inhibition 5.7 pIC50 19
pIC50 5.7 (IC50 2x10-6 M) [19]
Description: Inhibition of squalene synthase in rat liver microsome measured by convertion of [3H]FPP to squalene
Conditions: Substrate concentrations: 0.5mM NADPH, 0.5µM FPP. pH 7.4, 37°C
compound 19 [PMID: 18754614] Small molecule or natural product Rn Inhibition 5.5 pIC50 19
pIC50 5.5 (IC50 3x10-6 M) [19]
Description: Inhibition of squalene synthase in rat liver microsome measured by convertion of [3H]FPP to squalene
Conditions: Substrate concentrations: 0.5mM NADPH, 0.5µM FPP. pH 7.4, 37°C
compound 14 [PMID: 19191557] Small molecule or natural product Hs Inhibition 5.4 pIC50 38
pIC50 5.4 (IC50 3.7x10-6 M) [38]
Description: Inhibition of human recombinant squalene synthase expressed in Escherichia coli BL21 (DE3) cells assessed as formation of 1,10-dioic acid metabolite by liquid scintillation
Conditions: Substrate concentrations: 0.25mM NADPH, 0.1nmol FPP in a volume of 200µL. pH 7.4, 37°C
compound 20 [PMID: 20299227] Small molecule or natural product Rn Inhibition 5.4 pIC50 22
pIC50 5.4 (IC50 3.71x10-6 M) [22]
Description: Inhibition of squalene synthase in rat liver microsomes assessed as conversion of [1-3H]FPP to [3H]squalene level after 60 mins by liquid scintillation counting
Conditions: 0.02µCi FPP, 2mM NADPH. 30°C, assay performed in duplicate
compound 18 [PMID: 18754614] Small molecule or natural product Rn Inhibition 5.4 pIC50 19
pIC50 5.4 (IC50 4x10-6 M) [19]
Description: Inhibition of squalene synthase in rat liver microsome measured by convertion of [3H]FPP to squalene
Conditions: Substrate concentrations: 0.5mM NADPH, 0.5µM FPP. pH 7.4, 37°C
compound 20 [Shechter et al., 1996] Small molecule or natural product Rn Inhibition 5.3 pIC50 34
pIC50 5.3 (IC50 5x10-6 M) [34]
Description: Inhibitory activity against rat hepatic squalene synthase
compound 10 [PMID: 18754614] Small molecule or natural product Rn Inhibition 5.3 pIC50 19
pIC50 5.3 (IC50 5x10-6 M) [19]
Description: Inhibition of squalene synthase in rat liver microsome measured by convertion of [3H]FPP to squalene
Conditions: Substrate concentrations: 0.5mM NADPH, 0.5µM FPP. pH 7.4, 37°C
compound 5 [PMID: 18754614] Small molecule or natural product Rn Inhibition 5.3 pIC50 19
pIC50 5.3 (IC50 5x10-6 M) [19]
Description: Inhibition of squalene synthase in rat liver microsome measured by convertion of [3H]FPP to squalene
Conditions: Substrate concentrations: 0.5mM NADPH, 0.5µM FPP. pH 7.4, 37°C
compound 17 [PMID: 18754614] Small molecule or natural product Rn Inhibition 5.2 pIC50 19
pIC50 5.2 (IC50 6x10-6 M) [19]
Description: Inhibition of squalene synthase in rat liver microsome measured by convertion of [3H]FPP to squalene
Conditions: Substrate concentrations: 0.5mM NADPH, 0.5µM FPP. pH 7.4, 37°C
compound 7 [PMID: 18754614] Small molecule or natural product Rn Inhibition 5.2 pIC50 19
pIC50 5.2 (IC50 7x10-6 M) [19]
Description: Inhibition of squalene synthase in rat liver microsome measured by convertion of [3H]FPP to squalene
Conditions: Substrate concentrations: 0.5mM NADPH, 0.5µM FPP. pH 7.4, 37°C
compound 4 [PMID: 18754614] Small molecule or natural product Rn Inhibition 5.2 pIC50 19
pIC50 5.2 (IC50 7x10-6 M) [19]
Description: Inhibition of squalene synthase in rat liver microsome measured by convertion of [3H]FPP to squalene
Conditions: Substrate concentrations: 0.5mM NADPH, 0.5µM FPP. pH 7.4, 37°C
compound 19 [PMID: 19191557] Small molecule or natural product Hs Inhibition 4.9 pIC50 38
pIC50 4.9 (IC50 1.17x10-5 M) [38]
Description: Inhibition of human recombinant squalene synthase expressed in Escherichia coli BL21 (DE3) cells assessed as formation of 1,10-dioic acid metabolite by liquid scintillation
Conditions: Substrate concentrations: 0.25mM NADPH, 0.1nmol FPP in a volume of 200µL. pH 7.4, 37°C
compound 12 [PMID: 20299227] Small molecule or natural product Rn Inhibition 4.8 pIC50 22
pIC50 4.8 (IC50 1.768x10-5 M) [22]
Description: Inhibition of squalene synthase in rat liver microsomes assessed as conversion of [1-3H]FPP to [3H]squalene level after 60 mins by liquid scintillation counting
Conditions: 0.02µCi FPP, 2mM NADPH. 30°C, assay performed in duplicate
View species-specific inhibitor tables

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 Click here for help
Liver
Species:  Human
Technique:  Northern blot
References:  18
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Recombinant chromosome 8 syndrome
OMIM: 179613
Biologically Significant Variants Click here for help
Type:  Single nucleotide polymorphism
Species:  Human
Description:  Potassium residue at position 45 is substituted with arginine, resulting in increased total cholesterol and non-high density lipoprotein cholesterol.
References:  9

References

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14. Ichikawa M, Ohtsuka M, Ohki H, Haginoya N, Itoh M, Sugita K, Usui H, Suzuki M, Terayama K, Kanda A. (2012) Discovery of novel tricyclic compounds as squalene synthase inhibitors. Bioorg Med Chem, 20 (9): 3072-93. [PMID:22464687]

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