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2.5.1.59: protein geranylgeranyltransferase type I

This is an abbreviated version!
For detailed information about protein geranylgeranyltransferase type I, go to the full flat file.

Word Map on EC 2.5.1.59

Reaction

geranylgeranyl diphosphate
+
protein-cysteine
=
S-geranylgeranyl-protein
 +
diphosphate

Synonyms

CAAX geranylgeranyltransferase, CaaX prenyltransferase, CaGGTase-I, CDC43, geranylgeranyl protein transferase type I, geranylgeranyltransferase I, geranylgeranyltransferase type I, geranylgeranyltransferase type-I, geranylgeranyltransferase-1, geranylgeranyltransferase-I, geranylgeranyltransferaseI, GGT, GGT I, GGTalpha, GGTase, GGTase I, Ggtase-1, GGTase-I, GGTaseI, GGTbeta, GGTI, mammalian GGTase-I, PGGT, PGGT beta, PGGT I, PGGT-I, PGGTase-I, PGGTaseI, Ppggb, protein geranylgeranyltransferase, protein geranylgeranyltransferase I, protein geranylgeranyltransferase type I, protein geranylgeranyltransferase type-I, protein geranylgeranyltransferase-I, type I protein geranylgeranyltransferase

ECTree

     2 Transferases
         2.5 Transferring alkyl or aryl groups, other than methyl groups
             2.5.1 Transferring alkyl or aryl groups, other than methyl groups (only sub-subclass identified to date)
                2.5.1.59 protein geranylgeranyltransferase type I

Inhibitors

Inhibitors on EC 2.5.1.59 - protein geranylgeranyltransferase type I

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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2R,3R,4S,5R)-2-(3,4-dichlorophenyl)-4-(hexylsulfanyl)-1-[(4-methylphenyl)sulfonyl]-5-propylpyrrolidine-3-carboxylic acid
-
-
(2R,3R,4S,5R)-2-(4-bromophenyl)-1-[(4-methylphenyl)sulfonyl]-4-(pentylsulfanyl)-5-propylpyrrolidine-3-carboxylic acid
-
-
(2R,3R,4S,5R)-2-(4-bromophenyl)-4-(hexylsulfanyl)-1-[(4-methylphenyl)sulfonyl]-5-propylpyrrolidine-3-carboxylic acid
-
-
(2R,3R,4S,5R)-2-(4-bromophenyl)-4-[(4-methoxyphenyl)sulfanyl]-1-[(4-methylphenyl)sulfonyl]-5-propylpyrrolidine-3-carboxylic acid
-
-
(2R,3R,4S,5R)-2-(4-bromophenyl)-5-ethyl-4-(hexylsulfanyl)-1-[(4-methylphenyl)sulfonyl]pyrrolidine-3-carboxylic acid
-
-
(2R,3R,4S,5R)-2-(4-bromophenyl)-5-hexyl-4-(hexylsulfanyl)-1-[(4-methylphenyl)sulfonyl]pyrrolidine-3-carboxylic acid
-
-
(2R,3R,4S,5R)-4-[(3-tert-butoxy-3-oxopropyl)sulfanyl]-2-(3-chlorophenyl)-5-(cyclopentylmethyl)-1-[(4-methylphenyl)sulfonyl]pyrrolidine-3-carboxylic acid
-
-
(2R,3R,4S,5R)-4-[(3-tert-butoxy-3-oxopropyl)sulfanyl]-2-(4-chlorophenyl)-1-[(4-chlorophenyl)sulfonyl]-5-(cyclopentylmethyl)pyrrolidine-3-carboxylic acid
-
-
(2R,3R,4S,5R)-4-[(3-tert-butoxy-3-oxopropyl)sulfanyl]-2-(4-chlorophenyl)-5-(cyclopentylmethyl)-1-(phenylsulfonyl)pyrrolidine-3-carboxylic acid
-
-
(2R,3R,5S)-5-tert-butyl-2-(4-chlorophenyl)-1-[(2-methylphenyl)sulfonyl]pyrrolidine-3-carboxylic acid
compete with the substrate protein rather than GGPP; compete with the substrate protein rather than GGPP
(2S,5R)-5-ethyl-2-(4-fluorophenyl)-1-tosyl-2,5-dihydro-1H-pyrrole-3-carboxylic acid
-
IC50: 0.2 mM using RhoA as a substrate, IC50: 0.25 mM using Ki-Ras4B as a substrate
(2S,5S)-5-tert-butyl-2-(4-chlorophenyl)-1-[(2-methylphenyl)sulfonyl]-2,5-dihydro-1H-pyrrole-3-carboxylic acid
(2S,6S)-2,6-bis(4-chlorophenyl)-1-[(2-methylphenyl)sulfonyl]-1,2,5,6-tetrahydropyridine-3-carboxylic acid
-
IC50: 0.0003 mM using RhoA as a substrate, IC50: 0.002 mM using Ki-Ras4B as a substrate
(2S,6S)-6-(4-fluorophenyl)-1-[(4-methylphenyl)sulfonyl]-2-phenyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid
-
IC50: 0.12 mM using RhoA as a substrate, IC50: 0.08 mM using Ki-Ras4B as a substrate
(S)-N-(1-amino-3-(4-fluorophenyl)-1-oxopropan-2-yl)-4-((1-(3,4-dichlorophenyl)-4-(2-(methylthio)ethyl)-3-(pyridin-3-yl)-1H-pyrazol-5-yl)oxy)butanamide
potent GGT1 inhibitor, anti-proliferative efficacy against MDA-MB-231 cells has an IC50 value of 0.0076 mM
(S)-N-(1-amino-3-(4-methoxyphenyl)-1-oxopropan-2-yl)-4-((1-(3,4-dichlorophenyl)-4-(2-(methylthio)ethyl)-3-(pyridin-3-yl)-1H-pyrazol-5-yl)oxy)butanamide
potent GGT1 inhibitor
(S)-N-(4-(3,4-dichlorophenoxy)benzyl)-6-(1H-indol-3-yl)piperazine-2,5-dione
-
dual inhibitor for both farnesyl transferase and geranygeranyltransferase-I. Compound occupies both isoprenoid and peptide substrate binding sites
(S)-N-(4-(3-chlorophenoxy)benzyl)-6-(1H-indol-3-yl)piperazine-2,5-dione
-
dual inhibitor for both farnesyl transferase and geranygeranyltransferase-I
1-phosphono-(E,E,E)-geranylgeraniol
1-[2-[(Z)-[[4-(8-chloro-10,11-dihydrodibenzo[b,f]thiepin-10-yl)piperazin-1-yl]imino]methyl]phenoxy]-N,N-dimethylmethanamine
i.e L-269289, selective chemical inhibition of GGTase I by L-269289 potentiates echinocandin activity and renders echinocandin-resistant Candida albicans responsive to treatment in vitro and in animal models for disseminated infection
1-{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetylamino}-cyclohexanecarboxylic acid
-
IC50: 6525 nM
1-{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetylamino}-cyclohexanecarboxylic acid methyl ester
-
IC50: above 0.01 mM
11-aminoundecylcarbonyl-L-cysteinyl-L-valyl-L-isoleucyl-L-leucine
-
competitive. bivalent inhibitor for simultaneous recognition of both exteriorand interior protein surface. Not inhibitory against farnesyltransferase
2-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(2-methylphenyl)sulfonyl]-1,2,5,6-tetrahydropyridine-3-carboxylic acid
compete with the substrate protein rather than GGPP; compete with the substrate protein rather than GGPP
2-aryl-4-aminobenzoic acid
-
IC50: 21 nM
2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-N-(3-methyl-butyl)-acetamide
-
IC50: above 0.01 mM
2-{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl] acetylamino}-4-methyl-pentanoic acid methyl ester
-
IC50: above 0.01 mM
2-{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetylamino}-3-phenyl-propionic acid
-
IC50: 0.0063 mM; IC50: 170 nM
2-{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetylamino}-3-phenyl-propionic acid methyl ester
-
IC50: 4500 nM; IC50: above 0.01 mM
2-{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetylamino}-4-methyl-pentanoic acid
-
IC50: 2700 nM; IC50: 580 nM
2-{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetylamino}-4-methyl-pentanoic acid methyl ester
-
IC50: above 0.01 mM
2-{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetylamino}-4-methylsulfanyl-butyric acid
-
IC50: 3350 nM
2-{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetylamino}-4-methylsulfanyl-butyric acid methyl ester
-
IC50: above 0.01 mM
3-(4'-farnesyloxy-3'-methoxyphenyl)-2-trans propenoic acid
-
0.1 mM, 83.9% inhibition
3-(4'-farnesyloxy-3'-OH-phenyl)-2-trans propenoic acid
-
0.1 mM, 93.5% inhibition
3-(4'-geranyloxy-3'-methoxyphenyl)-2-trans propenoic acid
-
0.1 mM, 78.6% inhibition
3-(4'-geranyloxy-3'-methoxyphenyl)-2-trans propenoic acid ethyl ester
-
0.1 mM, 3% inhibition
3-(4'-geranyloxy-3'-OH-phenyl)-2-trans propenoic acid
-
0.1 mM, 72.4% inhibition
3-(4'-geranyloxy-3'-OH-phenyl)-2-trans propenoic acid ethyl ester
-
0.1 mM, 7.5% inhibition
3-(4'-isopentenyloxy-3'-OH-phenyl)-2-trans propenoic acid
-
0.1 mM, 46.4% inhibition
3-aza-geranylgeranyl-diphosphate
-
competitive inhibitor with respect to geranylgeranyl diphosphate, non-competitive to Cys-Val-Phe-Leu
3-chloro-N-[2-oxo-2-[2-[[1-phenyl-3-(4-propoxyphenyl)pyrazol-4-yl]methylidene]hydrazinyl]ethyl]benzamide
-
GGTI-DU.Sig1, PubChem CID 3311883, inhibitor of protein geranylgeranyltransferase type I
4-[2-[4-(3-chlorophenyl)-3-oxopiperazin-1-yl]-2-(1H-imidazol-5-yl)ethyl]benzonitrile
is bound to the peptide-binding site by competing with the CAAX substrate in the 4-[2-[4-(3-chlorophenyl)-3-oxopiperazin-1-yl]-2-(1H-imidazol-5-yl)ethyl]benzonitrile-FTase complex, cf. EC 2.5.1.58, but is bound in the lipid-binding pocket together with a portion of the peptide-binding site in the 4-[2-[4-(3-chlorophenyl)-3-oxopiperazin-1-yl]-2-(1H-imidazol-5-yl)ethyl]benzonitrile-GGTase-I complex; is bound to the peptide-binding site by competing with the CAAX substrate in the 4-[2-[4-(3-chlorophenyl)-3-oxopiperazin-1-yl]-2-(1H-imidazol-5-yl)ethyl]benzonitrile–FTase complex, cf. EC 2.5.1.58, but is bound in the lipid-binding pocket together with a portion of the peptide-binding site in the L-4-[2-[4-(3-chlorophenyl)-3-oxopiperazin-1-yl]-2-(1H-imidazol-5-yl)ethyl]benzonitrile-GGTase-I complex
4-[[([5-[(4-ethylphenoxy)methyl]-4-(1-phenylethyl)-4H-pyrazol-3-yl]sulfanyl)acetyl]amino]benzamide
-
inhibitor identified using quantitative structure-activity realtionship models and virtual screening of chemicals. confirmation of predicted data by experiment
4-[[2-[[5-(2-methoxyphenyl)-4-phenethyl-1,2,4-triazol-3-yl]sulfanyl]acetyl]amino]benzamide
-
GGTI-DU.En1, PubChem CID 2118978, inhibitor of protein geranylgeranyltransferase type I
4-[[2-[[5-[(4-ethylphenoxy)methyl]-4-(1-phenylethyl)-1,2,4-triazol-3-yl]sulfanyl]acetyl]amino]benzamide
-
GGTI-DU.En2, PubChem CID 3455185, inhibitor of protein geranylgeranyltransferase type I, no or little activity against protein farnesyltransferase
auraptene
-
0.1 mM, 18.6% inhibition
boropinic acid
-
0.1 mM, 31% inhibition
collinin
-
0.1 mM, 34.2% inhibition
Cys-3-(aminomethyl)benzoic acid-Leu
-
noncompetitive to geranylgeranyl diphosphate, competitive to dansyl-Gly-Cys-Ile-Ile-Leu
Cys-Val-Phe-Leu
-
noncompetitive inhibitor with respect to geranylgeranyl diphosphate, 50% inhibition at 0.0001 mM, competitive to Cys-Val-Phe-Leu
diethyl dicarbonate
-
80% loss of activity at 5 mM
GGTi-2147
GGTI-2151
16.3% inhibition at 50 nM
GGTI-2154
14.7% inhibition at 50 nM
GGTI-2418
a GGTI inhibitor, in clinical trials as potential anti-tumor agent in breast cancer; a GGTI inhibitor, in clinical trials as potential anti-tumor agent in breast cancer
GGTI-297
-
-
GGTI-298
GGTI-DU40
L-269289
L-cysteinyl-L-valyl-L-isoleucyl-L-leucine
-
-
manumycin A
the cdc43DELTA mutant is 2fold more susceptible to this farnesyltransferase inhibitor than the wild-type
methyl N-([2-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(2-methylphenyl)sulfonyl]-1,2,5,6-tetrahydropyridin-3-yl]carbonyl)leucinate
with anti-tumor activity; with anti-tumor activity
N-(12-ammoniododecanoyl)-D-cysteinyl-L-valyl-L-isoleucyl-L-leucine trifluoroacetate
-
-
N-(12-[[(3-[[(3R)-3-ammonio-4-phenylbutyl]oxy]-4,5-bis[[(3S)-3-ammonio-4-phenylbutyl]oxy]phenyl)carbonyl]amino]dodecanoyl)-L-cysteinyl-L-valyl-L-isoleucyl-L-leucine tris(trifluoroacetate)
-
-
N-(2,5-dichlorophenyl)-N'-[[3-(4-methylphenyl)-1-phenylpyrazol-4-yl]methylideneamino]oxamide
-
GGTI-DU.Sig2, PubChem CID 4277701, inhibitor of protein geranylgeranyltransferase type I
N-(4-[[(3-[[(3R)-3-ammonio-4-phenylbutyl]oxy]-4,5-bis[[(3S)-3-ammonio-4-phenylbutyl]oxy]phenyl)carbonyl]amino]butanoyl)-L-cysteinyl-L-valyl-L-isoleucyl-L-leucine tris(trifluoroacetate)
-
-
N-([(2S)-2-benzyl-4-[(4-methyl-1H-imidazol-5-yl)methyl]-3-oxopiperazin-1-yl]carbonyl)-L-leucine
-
N-([5-[(1H-imidazol-5-ylamino)methyl]-2'-methylbiphenyl-2-yl]carbonyl)-L-leucine
a non-thiol-containing peptidomi-metic, it can inhibit human tumor growth in mice and the combination therapy with cytotoxic agents is more beneficial than monotherapy. N-([5-[(1H-imidazol-5-ylamino)methyl]-2'-methylbiphenyl-2-yl]carbonyl)-L-leucine is able to induce breast carcinoma apoptosis and tumor regression in H-Ras transgenic mice; a non-thiol-containing peptidomi-metic, it can inhibit human tumor growth in mice and the combination therapy with cytotoxic agents is more beneficial than monotherapy. N-([5-[(1H-imidazol-5-ylamino)methyl]-2'-methylbiphenyl-2-yl]carbonyl)-L-leucine is able to induce breast carcinoma apoptosis and tumor regression in H-Ras transgenic mice
N-benzyl-2-[(2-chlorobenzyl)[[5-(4-methylphenyl)-2H-tetrazol-2-yl]acetyl]amino]butanamide
-
inhibitor identified using quantitative structure-activity realtionship models and virtual screening of chemicals. confirmation of predicted data by experiment
N-benzyl-2-[(2-chlorophenyl)methyl-[2-[5-(4-methylphenyl)tetrazol-2-yl]acetyl]amino]butanamide
-
GGTI-DU.As2, PubChem CID 3180738, inhibitor of protein geranylgeranyltransferase type I, no or little activity against protein farnesyltransferase
N-[(5-[[(2R)-2-amino-3-sulfanylpropyl]amino]biphenyl-2-yl)carbonyl]-L-leucine
-
N-[(E)-1-(benzylcarbamoyl)-2-[5-(3,4-dichlorophenyl)furan-2-yl]ethenyl]-4-methylbenzamide
-
inhibitor identified using quantitative structure-activity realtionship models and virtual screening of chemicals. confirmation of predicted data by experiment
N-[12-([[3,4,5-tris(3-ammoniopropoxy)phenyl]carbonyl]amino)dodecanoyl]-L-cysteinyl-L-valyl-L-isoleucyl-L-leucine tris(trifluoroacetate)
-
-
N-[2-(benzylamino)-2-oxoethyl]-2-[5-(4-chlorophenyl)tetrazol-2-yl]-N-(4-propan-2-ylphenyl)acetamide
-
GGTI-DU.As1, PubChem CID 3180720, inhibitor of protein geranylgeranyltransferase type I
N-[3-(benzylamino)-1-[5-(3,4-dichlorophenyl)furan-2-yl]-3-oxoprop-1-en-2-yl]-4-methylbenzamide
-
GGTI-DU.Sig3, PubChem CID 5143450, inhibitor of protein geranylgeranyltransferase type I, no or little activity against protein farnesyltransferase
N-[6-(3,4,5-tris(3-amino-1-propoxy)benzoylamino)-undecylcarbonyl]-L-cysteinyl-L-valyl-L-isoleucyl-L-leucine
-
competitive, bivalent inhibitor for simultaneous recognition of both exterior and interior protein surface. Not inhibitory against farnesyltransferase
N-[6-(3,4,5-tris(3-amino-4-phenyl-1-butoxy)benzoylamino)-hexylcarbonyl]-L-cysteinyl-L-valyl-L-isoleucyl-L-leucine trifluoroacetate
-
-
N-[6-(3,4,5-tris(3-amino-4-phenyl-1-butoxy)benzoylamino)-propylcarbonyl]-L-cysteinyl-L-valyl-L-isoleucyl-L-leucine
-
bivalent inhibitor for simultaneous recognition of both exterior and interior protein surface. Not inhibitory against farnesyltransferase
N-[6-(3,4,5-tris(3-amino-4-phenyl-1-butoxy)benzoylamino)-undecylcarbonyl]-L-cysteinyl-L-valyl-L-isoleucyl-L-leucine
-
competitive, bivalent inhibitor for simultaneous recognition of both exterior and interior protein surface. Not inhibitory against farnesyltransferase
N-[[4-(imidazol-4-yl)methylamino]-2-(1-naphthyl)benzoyl]leucine
-
Na-(4-[[1-(3,4-dichlorophenyl)-4-[2-(methylsulfanyl)ethyl]-3-(pyridin-3-yl)-1H-pyrazol-5-yl]oxy]butanoyl)-L-phenylalaninamide
-
Na-([(5R)-5-tert-butyl-2-(4-chlorophenyl)-1-[(2-methylphenyl)sulfonyl]-2,5-dihydro-1H-pyrrol-3-yl]carbonyl)-L-phenylalaninamide
with anti-tumor activity; with anti-tumor activity
NPFREKKFFCAIL
-
biotin-gamma6, substrate inhibition at high peptide concentration
P61A6
derived from an allenoate-derived compound library, shows efficiency of the enzyme inhibitor to inhibit tumor growth demonstrated using human pancreatic cancer xenograft; derived from an allenoate-derived compound library, shows efficiency of the enzyme inhibitor to inhibit tumor growth demonstrated using human pancreatic cancer xenograft
PD-083176
-
noncompetitive to geranylgeranyl diphosphate, competitive to GST-CDC42, modest inhibitor
Phenylglyoxal
-
80% loss of activity, inactivation of inhibition in the presence of geranylgeranyl diphosphate
tetrapeptide CVIL
superposition of the crystal structures of the CVIL-GGTase-I complex; superposition of the crystal structures of the CVIL-GGTase-I complex
Thr-Lys-Cys-Val-Ile-Leu
-
potent competitor, 50% inhibition at 0.001 mM
Thr-Lys-Cys-Val-Ile-Met
-
potent competitor, 50% inhibition at 0.008 mM
tipifarnib
the cdc43DELTA mutant is 4fold more susceptible to this farnesyltransferase inhibitor than the wild-type
umbelliprenine
-
0.1 mM, 13.4% inhibition
[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetic acid benzyl ester
-
IC50: above 0.01 mM
{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetylamino}-acetic acid
-
IC50: above 0.01 mM
{2-[3-(1H-imidazol-4-ylmethyl)-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl]-acetylamino}-acetic acid methyl ester
-
IC50: above 0.01 mM
additional information
-