farnesyl diphosphate synthase | Lanosterol biosynthesis pathway | IUPHAR/MMV Guide to MALARIA PHARMACOLOGY

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farnesyl diphosphate synthase

Target id: 644

Nomenclature: farnesyl diphosphate synthase

Family: Lanosterol biosynthesis pathway

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

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 419 1q22 FDPS farnesyl diphosphate synthase
Mouse - 353 3 F1; 3 42.6 cM Fdps farnesyl diphosphate synthetase
Rat - 353 2q34 Fdps farnesyl diphosphate synthase
Previous and Unofficial Names
geranyl transferase I | HsFPS | prenyltransferase | (2E,6E)-farnesyl diphosphate synthase | dimethylallyltranstransferase | FPP synthase | FPS | geranyltranstransferase | testis-specific farnesyl pyrophosphate synthetase | Fdpsl1
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures
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
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
Substrate Sp. Property Value Units Standard property Standard value Assay description Assay conditions Comments Reference
isopentenyl diphosphate Hs Km 6x10-7 M pKm 6.2 7
isopentenyl diphosphate Hs Km 9.4x10-7 M pKm 6.0 2
isopentenyl diphosphate Rn Km 3x10-6 M pKm 5.5 in vitro assay pH 7.5 Concentration of substates: 20µM IPP, 25µM GPP 14
dimethylallyl diphosphate 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 Hs Km 4.4x10-7 M pKm 6.4 in vitro assay pH 7.8 2
geranyl diphosphate Rn Km 6x10-7 M pKm 6.2 in vitro assay pH 7.5 Concentration of substates: 20µM IPP, 25µM GPP 14
geranyl diphosphate Hs Km 7.2x10-7 M pKm 6.1 7
Cofactors
Cofactor Species Comments Reference
Mg2+ Human Also characterised in rats 2,4,14
Mn2+ Human 2

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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
zoledronic acid 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 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 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 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 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 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 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 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 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 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 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 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 Hs Inhibition 6.7 pKi 5
pKi 6.7 (Ki 1.95x10-7 M) [5]
isopentenyl diphosphate Hs Inhibition 6.2 pKi 1
pKi 6.2 (7x10-7 M) [1]
Description: value not verified
diphosphoric acid 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 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 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] 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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] 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 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 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] 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 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
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]

7. Glickman JF, Schmid A. (2007) Farnesyl pyrophosphate synthase: real-time kinetics and inhibition by nitrogen-containing bisphosphonates in a scintillation assay. Assay Drug Dev Technol, 5 (2): 205-14. [PMID:17477829]

8. Lin YS, Park J, De Schutter JW, Huang XF, Berghuis AM, Sebag M, Tsantrizos YS. (2012) Design and synthesis of active site inhibitors of the human farnesyl pyrophosphate synthase: apoptosis and inhibition of ERK phosphorylation in multiple myeloma cells. J. Med. Chem., 55 (7): 3201-15. [PMID:22390415]

9. Lühe A, Künkele KP, Haiker M, Schad K, Zihlmann C, Bauss F, Suter L, Pfister T. (2008) Preclinical evidence for nitrogen-containing bisphosphonate inhibition of farnesyl diphosphate (FPP) synthase in the kidney: implications for renal safety. Toxicol In Vitro, 22 (4): 899-909. [PMID:18325729]

10. Marma MS, Xia Z, Stewart C, Coxon F, Dunford JE, Baron R, Kashemirov BA, Ebetino FH, Triffitt JT, Russell RG et al.. (2007) Synthesis and biological evaluation of alpha-halogenated bisphosphonate and phosphonocarboxylate analogues of risedronate. J. Med. Chem., 50 (24): 5967-75. [PMID:17975902]

11. McKenna CE, Kashemirov BA, Błazewska KM, Mallard-Favier I, Stewart CA, Rojas J, Lundy MW, Ebetino FH, Baron RA, Dunford JE et al.. (2010) Synthesis, chiral high performance liquid chromatographic resolution and enantiospecific activity of a potent new geranylgeranyl transferase inhibitor, 2-hydroxy-3-imidazo[1,2-a]pyridin-3-yl-2-phosphonopropionic acid. J. Med. Chem., 53 (9): 3454-64. [PMID:20394422]

12. Peukert S, Sun Y, Zhang R, Hurley B, Sabio M, Shen X, Gray C, Dzink-Fox J, Tao J, Cebula R et al.. (2008) Design and structure-activity relationships of potent and selective inhibitors of undecaprenyl pyrophosphate synthase (UPPS): tetramic, tetronic acids and dihydropyridin-2-ones. Bioorg. Med. Chem. Lett., 18 (6): 1840-4. [PMID:18295483]

13. Rondeau JM, Bitsch F, Bourgier E, Geiser M, Hemmig R, Kroemer M, Lehmann S, Ramage P, Rieffel S, Strauss A et al.. (2006) Structural basis for the exceptional in vivo efficacy of bisphosphonate drugs. ChemMedChem, 1 (2): 267-73. [PMID:16892359]

14. Runquist M, Ericsson J, Thelin A, Chojnacki T, Dallner G. (1994) Isoprenoid biosynthesis in rat liver mitochondria. Studies on farnesyl pyrophosphate synthase and trans-prenyltransferase. J. Biol. Chem., 269 (8): 5804-9. [PMID:8119922]

15. Sheares BT, White SS, Molowa DT, Chan K, Ding VD, Kroon PA, Bostedor RG, Karkas JD. (1989) Cloning, analysis, and bacterial expression of human farnesyl pyrophosphate synthetase and its regulation in Hep G2 cells. Biochemistry, 28 (20): 8129-35. [PMID:2690933]

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