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farnesyl diphosphate synthase

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Target id: 644

Nomenclature: farnesyl diphosphate synthase

Family: Lanosterol biosynthesis pathway

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 419 1q22 FDPS farnesyl diphosphate synthase
Mouse - 353 3 39.01 cM Fdps farnesyl diphosphate synthetase
Rat - 353 2q34 Fdps farnesyl diphosphate synthase
Previous and Unofficial Names Click here for help
geranyl transferase I | HsFPS | prenyltransferase | (2E,6E)-farnesyl diphosphate synthase | dimethylallyltranstransferase | FPP synthase | FPS | geranyltranstransferase | testis-specific farnesyl pyrophosphate synthetase | Fdpsl1
Database Links Click here for help
Alphafold P14324 (Hs), Q920E5 (Mm), P05369 (Rn)
BRENDA 2.5.1.1, 2.5.1.10
CATH/Gene3D 1.10.600.10
ChEMBL Target CHEMBL1782 (Hs), CHEMBL4523414 (Mm), CHEMBL1075093 (Rn)
DrugBank Target P14324 (Hs)
Ensembl Gene ENSG00000160752 (Hs), ENSMUSG00000059743 (Mm), ENSRNOG00000043377 (Rn)
Entrez Gene 2224 (Hs), 110196 (Mm), 83791 (Rn)
Human Protein Atlas ENSG00000160752 (Hs)
KEGG Enzyme 2.5.1.1, 2.5.1.10
KEGG Gene hsa:2224 (Hs), mmu:110196 (Mm), rno:83791 (Rn)
OMIM 134629 (Hs)
Pharos P14324 (Hs)
RefSeq Nucleotide NM_001242824 (Hs), NM_002004 (Hs), NM_001135821 (Hs), NM_001135822 (Hs), NM_001242825 (Hs), NM_134469 (Mm), NM_001253751 (Mm), NM_031840 (Rn)
RefSeq Protein NP_001995 (Hs), NP_001229753 (Hs), NP_001229754 (Hs), NP_001129294 (Hs), NP_001129293 (Hs), NP_608219 (Mm), NP_001240680 (Mm), NP_114028 (Rn)
SynPHARM 7122 (in complex with alendronate)
78402 (in complex with alendronate)
7117 (in complex with diphosphoric acid)
7116 (in complex with diphosphoric acid)
79510 (in complex with ibandronic acid)
7089 (in complex with isopentenyl diphosphate)
7125 (in complex with minodronic acid)
79436 (in complex with pamidronic acid)
78401 (in complex with risedronate)
7130 (in complex with risedronate)
7131 (in complex with risedronate)
7136 (in complex with risedronate)
7092 (in complex with risedronate)
7093 (in complex with risedronate)
7091 (in complex with zoledronic acid)
7127 (in complex with zoledronic acid)
7090 (in complex with zoledronic acid)
7126 (in complex with zoledronic acid)
UniProtKB P14324 (Hs), Q920E5 (Mm), P05369 (Rn)
Wikipedia FDPS (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of Unliganded Human FPPS
PDB Id:  2F7M
Resolution:  2.3Å
Species:  Human
References:  13
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human FPPS in complex with YS_04_70
PDB Id:  4DEM
Ligand:  compound 13k [PMID: 22390415]
Resolution:  1.85Å
Species:  Human
References:  8
Enzyme Reaction Click here for help
EC Number: 2.5.1.1 Dimethylallyl diphosphate + isopentenyl diphosphate = geranyl diphosphate + diphosphate
EC Number: 2.5.1.10 Geranyl diphosphate + isopentenyl diphosphate -> trans,trans-farnesyl diphosphate + diphosphate
Substrates and Reaction Kinetics Click here for help
Substrate Sp. Property Value Units Standard property Standard value Assay description Assay conditions Comments Reference
isopentenyl diphosphate Substrate is endogenous in the given species Hs Km 6x10-7 M pKm 6.2 7
isopentenyl diphosphate Substrate is endogenous in the given species Hs Km 9.4x10-7 M pKm 6.0 2
isopentenyl diphosphate Substrate is endogenous in the given species Rn Km 3x10-6 M pKm 5.5 in vitro assay pH 7.5 Concentration of substates: 20µM IPP, 25µM GPP 14
dimethylallyl diphosphate Substrate is endogenous in the given species Rn Km 1.2x10-6 M pKm 5.9 in vitro assay pH 7.5 Concentration of substates: 20µM IPP, 25µM GPP 14
geranyl diphosphate Substrate is endogenous in the given species Hs Km 4.4x10-7 M pKm 6.4 in vitro assay pH 7.8 2
geranyl diphosphate Substrate is endogenous in the given species Rn Km 6x10-7 M pKm 6.2 in vitro assay pH 7.5 Concentration of substates: 20µM IPP, 25µM GPP 14
geranyl diphosphate Substrate is endogenous in the given species Hs Km 7.2x10-7 M pKm 6.1 7
Cofactors Click here for help
Cofactor Species Comments Reference
Mg2+ Human Also characterised in rats 2,4,14
Mn2+ Human 2

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
zoledronic acid Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 7.1 – 10.1 pKi 5
⤷ pKi 10.1 (Ki 7x10-11 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: pH 7.7, 37ºC. final Ki
pKi 7.1 (Ki 8.59x10-8 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: pH 7.7, 37ºC. initial Ki
NE97220 Small molecule or natural product Ligand has a PDB structure Hs Inhibition 7.9 – 9.0 pKi 5
⤷ pKi 9.0 (Ki 1.09x10-9 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.7, 37ºC. final Ki
pKi 7.9 (Ki 1.21x10-8 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.7, 37ºC. initial Ki
risedronate Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 7.1 – 9.4 pKi 5
⤷ pKi 9.4 (Ki 3.6x10-10 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.5, 37°C. final Ki
pKi 7.1 (Ki 8.22x10-8 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.5, 37°C. initial Ki
NE58018 Small molecule or natural product Hs Inhibition 7.2 – 9.1 pKi 5
⤷ pKi 9.1 (Ki 7.4x10-10 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.5, 37°C. final Ki
pKi 7.2 (Ki 5.93x10-8 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.5, 37°C. initial Ki
NE58062 Small molecule or natural product Hs Inhibition 7.1 – 9.0 pKi 5
⤷ pKi 9.0 (Ki 1x10-9 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.7, 37ºC. final Ki
pKi 7.1 (Ki 8.36x10-8 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.7, 37ºC. initial Ki
NE11808 Small molecule or natural product Ligand has a PDB structure Hs Inhibition 7.4 – 8.6 pKi 5
⤷ pKi 8.6 (Ki 2.3x10-9 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.5, 37°C. final Ki
pKi 7.4 (Ki 3.69x10-8 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.5, 37°C. initial Ki
piridronic acid Small molecule or natural product Hs Inhibition 7.4 – 8.4 pKi 5
⤷ pKi 8.4 (Ki 4.45x10-9 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.7, 37ºC. final Ki
pKi 7.4 (Ki 3.895x10-8 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.7, 37ºC. initial Ki
NE58027 Small molecule or natural product Hs Inhibition 6.9 – 8.8 pKi 5
⤷ pKi 8.8 (Ki 1.6x10-9 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.2, 37°C; pH 7.5, 37°C. final Ki
pKi 6.9 (Ki 1.367x10-7 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.2, 37°C; pH 7.5, 37°C. initial Ki
NE21650 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.2 – 8.5 pKi 5
⤷ pKi 8.5 (Ki 3.4x10-9 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.5, 37°C. final Ki
pKi 7.2 (Ki 6.46x10-8 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.5, 37°C. initial Ki
NE58043 Small molecule or natural product Hs Inhibition 7.5 – 8.1 pKi 5
⤷ pKi 8.1 (Ki 7.4x10-9 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.7, 37ºC. final Ki
pKi 7.5 (Ki 3.476x10-8 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.7, 37ºC. final Ki
cimadronate Small molecule or natural product Hs Inhibition 7.2 – 8.0 pKi 5
⤷ pKi 8.0 (Ki 1x10-8 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: pH 7.5, 37°C. final Ki
pKi 7.2 (Ki 6.24x10-8 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21
Conditions: pH 7.5, 37°C. initial Ki
NE10575 Small molecule or natural product Ligand has a PDB structure Hs Inhibition 6.8 – 8.4 pKi 5
⤷ pKi 8.4 (Ki 3.9x10-9 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.7, 37°C. final Ki
pKi 6.8 (Ki 1.77x10-7 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.7, 37°C. initial Ki
ibandronic acid Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 6.7 pKi 5
⤷ pKi 6.7 (Ki 1.95x10-7 M) [5]
isopentenyl diphosphate Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Inhibition 6.2 pKi 1
⤷ pKi 6.2 (7x10-7 M) [1]
Description: value not verified
diphosphoric acid Small molecule or natural product Ligand has a PDB structure Hs Inhibition 4.5 – 7.4 pKi 5
⤷ pKi 7.4 (Ki 4.05x10-8 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: pH 7.5, 37°C. initial Ki
pKi 4.5 (Ki 2.98x10-8 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: pH 7.5, 37°C. final Ki
NE10790 Small molecule or natural product Hs Inhibition 4.2 – 7.0 pKi 5
⤷ pKi 7.0 (Ki 9.75x10-8 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.5, 37°C. initial Ki
pKi 4.2 (Ki 6.1x10-8 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.2, 37°C; pH 7.5, 37°C. final Ki
minodronic acid Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.5 pIC50 11
⤷ pIC50 8.5 (IC50 3x10-9 M) [11]
Description: Inhibition of human FPPS after 10 mins using [14C]IPP as substrate by liquid scintillation counting
Conditions: Concentration of substrates: 50µM IPP and 50µGPP.
compound 5e [PMID: 17975902] Small molecule or natural product Hs Inhibition 7.8 pIC50 10
⤷ pIC50 7.8 (IC50 1.64x10-8 M) [10]
Description: Inhibition of human cloned FPPS expressed in Escherichia col BL2 (DE3)
Conditions: Substrate concentration: 10µM IPP and GPP. pH 7.7, 37°C
NE97220 Small molecule or natural product Ligand has a PDB structure Hs Inhibition 7.1 – 8.2 pIC50 5
⤷ pIC50 8.2 (IC50 6.2x10-9 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.7, 37°C. final IC50
pIC50 7.1 (IC50 7.52x10-8 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.7, 37°C. initial IC50
risedronate Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 6.3 – 8.4 pIC50 3,5-6
⤷ pIC50 8.4 (IC50 3.9x10-9 M) [3]
pIC50 8.2 (IC50 5.7x10-9 M) [6]
Description: in vitro assay, inhibition of recombinant human enzyme expressed in E.coli
Conditions: pH 7.7, 37ºC.
pIC50 8.2 (IC50 5.7x10-9 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: pH 7.7, 37°C. final IC50
pIC50 8.0 (IC50 1x10-8 M) [6]
Description: In vitro inhibition of recombinant human FDPS expressed in E.coli.
Conditions: pH 7.7, 37ºC.
pIC50 6.3 (IC50 4.529x10-7 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: pH 7.7, 37°C. initial IC50
zoledronic acid Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 6.3 – 8.4 pIC50 5,16
⤷ pIC50 8.4 (IC50 4.1x10-9 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.7, 37ºC. final IC50
pIC50 8.4 (IC50 4.1x10-9 M) [16]
Description: Inhibition of human FPP synthase expressed in Escherichia coli BL21 (DE3)
Conditions: Substrate concentrations: 50µM GPP and 50µ IPP .pH 7.7, 35ºC.
pIC50 6.3 (IC50 4.753x10-7 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.7, 37ºC. initial IC50
NE11808 Small molecule or natural product Ligand has a PDB structure Hs Inhibition 6.7 – 7.8 pIC50 5
⤷ pIC50 7.8 (IC50 1.5x10-8 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: pH 7.5, 37°C. final IC50
pIC50 6.7 (IC50 1.901x10-7 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: pH 7.5, 37°C. initial IC50
NE58018 Small molecule or natural product Hs Inhibition 6.5 – 8.0 pIC50 5
⤷ pIC50 8.0 (IC50 9.2x10-9 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.7, 37°C. final IC50
pIC50 6.5 (IC50 3.491x10-7 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.7, 37°C. initial IC50
NE58062 Small molecule or natural product Hs Inhibition 6.3 – 8.0 pIC50 5
⤷ pIC50 8.0 (IC50 1.03x10-8 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.5, 37°C. final IC50
pIC50 6.3 (IC50 5.408x10-7 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.5, 37°C. initial IC50
NE58043 Small molecule or natural product Hs Inhibition 6.8 – 7.5 pIC50 5
⤷ pIC50 7.5 (IC50 3.26x10-8 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. final IC50
pIC50 6.8 (IC50 1.734x10-7 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. initial IC50
piridronic acid Small molecule or natural product Hs Inhibition 6.6 – 7.5 pIC50 5
⤷ pIC50 7.5 (IC50 3.04x10-8 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.7, 37ºC. final IC50
pIC50 6.6 (IC50 2.588x10-7 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.7, 37ºC. initial IC50
NE21650 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.4 – 7.7 pIC50 5
⤷ pIC50 7.7 (IC50 2.16x10-8 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: pH 7.7, 37°C. final IC50
pIC50 6.4 (IC50 3.707x10-7 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: pH 7.7, 37°C. initial IC50
NE58027 Small molecule or natural product Hs Inhibition 6.2 – 7.9 pIC50 5
⤷ pIC50 7.9 (IC50 1.37x10-8 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.5, 37°C. final IC50
pIC50 6.2 (IC50 5.916x10-7 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.5, 37°C. initial IC50
cimadronate Small molecule or natural product Hs Inhibition 6.4 – 7.2 pIC50 5
⤷ pIC50 7.2 (IC50 6.11x10-8 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: pH 7.5, 37°C. final IC50
pIC50 6.4 (IC50 3.656x10-7 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21
Conditions: initial ic50
alendronate Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 6.3 – 7.3 pIC50 3,6
⤷ pIC50 7.3 (IC50 5x10-8 M) [6]
Description: In vitro inhibition of recombinant human protein expressed in E coli.
Conditions: Substrate concentrations: 2nmol IPP and 2nmol GPP in a total volume of 50 µl. pH 7.7, 37ºC
pIC50 6.3 (IC50 4.6x10-7 M) [3]
NE10575 Small molecule or natural product Ligand has a PDB structure Hs Inhibition 5.8 – 7.7 pIC50 5
⤷ pIC50 7.7 (IC50 1.96x10-8 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.5, 37°C; pH 7.2, 37°C. final IC50
pIC50 5.8 (IC50 1.706x10-6 M) [5]
Description: Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins
Conditions: Concentration of substrates: 10µM GPP and IPP in a volume of 100µL. pH 7.5, 37°C; pH 7.2, 37°C. initial IC50
pamidronic acid Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 6.7 pIC50 5
⤷ pIC50 6.7 (IC50 2x10-7 M) [5]
Description: Inhibition of recombinant human FDPS expressed in E. coli.
compound 31 [PMID: 17963374] Small molecule or natural product Hs Inhibition 6.5 pIC50 18
⤷ pIC50 6.5 [18]
Description: Inhibition of human FPPS, measured through inhibition of tumour cell growth in NCI-H460 cell line . Not a direct enzyme inhibition assay.
zoledronic acid Small molecule or natural product Approved drug Ligand has a PDB structure Rn Inhibition 6.3 pIC50 9
⤷ pIC50 6.3 (IC50 5x10-7 M) [9]
Description: in vitro using kidney cell lines
Conditions: pH 7.7, 22°C
ibandronic acid Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Inhibition 5.1 pIC50 9
⤷ pIC50 5.1 (7.4x10-6 M) [9]
Description: in vitro using kidney cell lines
Conditions: pH 7.7, 22°C
compound 2 [PMID: 18295483] Small molecule or natural product Hs Inhibition 5.1 pIC50 12
⤷ pIC50 5.1 (IC50 8x10-6 M) [12]
Description: Inhibition of human FPPS
Conditions: Concentrations of substrates: 8µM DMAPP and 16µM IPP. pH 7.3
geranyl biphosphonate Small molecule or natural product Hs Inhibition 4.7 pIC50 17
⤷ pIC50 4.7 (IC50 2x10-5 M) [17]
Description: Inhibition of human recombinant FDPS expressed in BL21 gold bacteria
Conditions: Substrate concentrations: 20µM GPP and 40µM IPP. pH 7.5, 37ºC
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:  15

References

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1. Barnard GF. (1985) Prenyltransferase from human liver. Meth Enzymol, 110: 155-67. [PMID:4021811]

2. Barnard GF, Popják G. (1981) Human liver prenyltransferase and its characterization. Biochim Biophys Acta, 661 (1): 87-99. [PMID:7295734]

3. Bergstrom JD, Bostedor RG, Masarachia PJ, Reszka AA, Rodan G. (2000) Alendronate is a specific, nanomolar inhibitor of farnesyl diphosphate synthase. Arch Biochem Biophys, 373 (1): 231-41. [PMID:10620343]

4. Deprèle S, Kashemirov BA, Hogan JM, Ebetino FH, Barnett BL, Evdokimov A, McKenna CE. (2008) Farnesyl pyrophosphate synthase enantiospecificity with a chiral risedronate analog, [6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl(hydroxy)methylene]bis(phosphonic acid) (NE-10501): Synthetic, structural, and modeling studies. Bioorg Med Chem Lett, 18 (9): 2878-82. [PMID:18434151]

5. Dunford JE, Kwaasi AA, Rogers MJ, Barnett BL, Ebetino FH, Russell RG, Oppermann U, Kavanagh KL. (2008) Structure-activity relationships among the nitrogen containing bisphosphonates in clinical use and other analogues: time-dependent inhibition of human farnesyl pyrophosphate synthase. J Med Chem, 51 (7): 2187-95. [PMID:18327899]

6. Dunford JE, Thompson K, Coxon FP, Luckman SP, Hahn FM, Poulter CD, Ebetino FH, Rogers MJ. (2001) Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates. J Pharmacol Exp Ther, 296 (2): 235-42. [PMID:11160603]

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