Literature summary for 2.5.1.58 extracted from

Lucescu, L.; Ghinet, A.; Shova, S.; Magnez, R.; Thuru, X.; Farce, A.; Rigo, B.; Belei, D.; Dubois, J.; Bicu, E.
Exploring isoxazoles and pyrrolidinones decorated with the 4,6-dimethoxy-1,3,5-triazine unit as human farnesyltransferase inhibitors (2019), Arch. Pharm., 352, e1800227 .

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Crystallization (Commentary)

Crystallization (Comment)	Organism
molecular docking of inhibitors	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
4-[5-(4,6-dimethoxy-1,3,5-triazin-2-yl)-1,2-oxazol-3-yl]-N,N-dimethylaniline	in a model structure, the dimethylamine is in front of the zinc atom. The conformation is stabilized by two well-conserved hydrogen bond groups, one from the triazine to Arg 702	Homo sapiens
5-(4,6-dimethoxy-1,3,5-triazin-2-yl)-1-(4-methoxyphenyl)pyrrolidin-2-thione	in S-configuration, the compound binds rather low in the site of the enzyme, at the end of the farnesyldiphosphate far from the zinc. In R-configuration, there is a hydrogen bond between one the methoxy groups and Arg 702	Homo sapiens
5-(4,6-dimethoxy-1,3,5-triazin-2-yl)-1-[3-(trifluoromethyl)phenyl]pyrrolidine-2-thione	-	Homo sapiens
ethyl 3-(2,5-dimethoxyphenyl)-1,2-oxazole-5-carboxylate	-	Homo sapiens
Zn2+	inhibition of human farnesyltransferase by zinc complexation can be improved with triazine-isoxazole moieties. The replacement of the isoxazole unit by a pyrrolidin-2-one is detrimental to the inhibitory activity while the pyrrolidin-2-thione derivatives conserves the biological potential	Homo sapiens

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P49354 and P49356	P49354 i.e. alpha-subunit, P49356 i.e. beta-subunit	-

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor	Structure
0.0038	-	pH 7.5, 30°C	Homo sapiens	5-(4,6-dimethoxy-1,3,5-triazin-2-yl)-1-(4-methoxyphenyl)pyrrolidin-2-thione
0.0372	-	pH 7.5, 30°C	Homo sapiens	ethyl 3-(2,5-dimethoxyphenyl)-1,2-oxazole-5-carboxylate
0.0373	-	pH 7.5, 30°C	Homo sapiens	4-[5-(4,6-dimethoxy-1,3,5-triazin-2-yl)-1,2-oxazol-3-yl]-N,N-dimethylaniline
0.0411	-	pH 7.5, 30°C	Homo sapiens	5-(4,6-dimethoxy-1,3,5-triazin-2-yl)-1-[3-(trifluoromethyl)phenyl]pyrrolidine-2-thione

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Release 2023.1 (January 2023)