Literature summary for 2.4.1.1 extracted from

Anderka, O.; Loenze, P.; Klabunde, T.; Dreyer, M.K.; Defossa, E.; Wendt, K.U.; Schmoll, D.
Thermodynamic characterization of allosteric glycogen phosphorylase inhibitors (2008), Biochemistry, 47, 4683-4691.

Crystallization (Commentary)

Crystallization (Comment)	Organism
in complex with inhibitors 4-([[(2-chloro-4,5-difluorophenyl)carbonyl]carbamoyl]amino)-3-(trifluoromethoxy)benzoic acid, 1-[2-([[(2-chloro-4,5-difluorophenyl)carbonyl]carbamoyl]amino)-4-fluorophenyl]piperidine-4-carboxylic acid, and 1-(2-carboxyphenyl)-6-[(2-chloro-4,6-difluorophenyl)amino]-4-oxo-1,2,3,4-tetrahydroquinoline-3-carboxylic acid. Binding to inhibitor 4-([[(2-chloro-4,5-difluorophenyl)carbonyl]carbamoyl]amino)-3-(trifluoromethoxy)benzoic acid is exclusively enthalpic. The inhibitors 1-[2-([[(2-chloro-4,5-difluorophenyl)carbonyl]carbamoyl]amino)-4-fluorophenyl]piperidine-4-carboxylic acid, and 1-(2-carboxyphenyl)-6-[(2-chloro-4,6-difluorophenyl)amino]-4-oxo-1,2,3,4-tetrahydroquinoline-3-carboxylic acid fully exploit the volume of the binding pocket and show pronounced binding entropy	Homo sapiens

Crystallization (Comment)

Organism

in complex with inhibitors 4-([[(2-chloro-4,5-difluorophenyl)carbonyl]carbamoyl]amino)-3-(trifluoromethoxy)benzoic acid, 1-[2-([[(2-chloro-4,5-difluorophenyl)carbonyl]carbamoyl]amino)-4-fluorophenyl]piperidine-4-carboxylic acid, and 1-(2-carboxyphenyl)-6-[(2-chloro-4,6-difluorophenyl)amino]-4-oxo-1,2,3,4-tetrahydroquinoline-3-carboxylic acid. Binding to inhibitor 4-([[(2-chloro-4,5-difluorophenyl)carbonyl]carbamoyl]amino)-3-(trifluoromethoxy)benzoic acid is exclusively enthalpic. The inhibitors 1-[2-([[(2-chloro-4,5-difluorophenyl)carbonyl]carbamoyl]amino)-4-fluorophenyl]piperidine-4-carboxylic acid, and 1-(2-carboxyphenyl)-6-[(2-chloro-4,6-difluorophenyl)amino]-4-oxo-1,2,3,4-tetrahydroquinoline-3-carboxylic acid fully exploit the volume of the binding pocket and show pronounced binding entropy

Homo sapiens

Inhibitors

Inhibitors	Comment	Organism
1-(2-carboxyphenyl)-6-[(2-chloro-4,6-difluorophenyl)amino]-4-oxo-1,2,3,4-tetrahydroquinoline-3-carboxylic acid	i.e. AVE9423. Inhibitor fully exploits the volume of the binding pocket and show pronounced binding entropy	Homo sapiens
1-(2-carboxyphenyl)-6-[(2-chloro-4,6-difluorophenyl)amino]-4-oxo-1,2,3,4-tetrahydroquinoline-3-carboxylic acid	-	Oryctolagus cuniculus
1-[2-([[(2-chloro-4,5-difluorophenyl)carbonyl]carbamoyl]amino)-4-fluorophenyl]piperidine-4-carboxylic acid	i.e. AVE2865. Inhibitor fully exploits the volume of the binding pocket and show pronounced binding entropy	Homo sapiens
1-[2-([[(2-chloro-4,5-difluorophenyl)carbonyl]carbamoyl]amino)-4-fluorophenyl]piperidine-4-carboxylic acid	-	Oryctolagus cuniculus
4-([[(2-chloro-4,5-difluorophenyl)carbonyl]carbamoyl]amino)-3-(trifluoromethoxy)benzoic acid	i.e. AVE5688, binding to enzyme is exclusively enthalpic	Homo sapiens
4-([[(2-chloro-4,5-difluorophenyl)carbonyl]carbamoyl]amino)-3-(trifluoromethoxy)benzoic acid	-	Oryctolagus cuniculus

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P06737	-	-
Oryctolagus cuniculus	-	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
commercial preparation	isoforms phosphorylase a and b	Oryctolagus cuniculus	-
commercial preparation	isoforms phosphorylase a and b	Homo sapiens	-
muscle	-	Oryctolagus cuniculus	-
muscle	-	Homo sapiens	-

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor
0.000014	-	phosphorylase a, pH 7.4, 25°C	Oryctolagus cuniculus	1-[2-([[(2-chloro-4,5-difluorophenyl)carbonyl]carbamoyl]amino)-4-fluorophenyl]piperidine-4-carboxylic acid
0.000024	-	phosphorylase b, pH 7.4, 25°C	Oryctolagus cuniculus	1-[2-([[(2-chloro-4,5-difluorophenyl)carbonyl]carbamoyl]amino)-4-fluorophenyl]piperidine-4-carboxylic acid
0.000044	-	phosphorylase a, pH 7.4, 25°C	Oryctolagus cuniculus	1-(2-carboxyphenyl)-6-[(2-chloro-4,6-difluorophenyl)amino]-4-oxo-1,2,3,4-tetrahydroquinoline-3-carboxylic acid
0.000059	-	phosphorylase b, pH 7.4, 25°C	Oryctolagus cuniculus	1-(2-carboxyphenyl)-6-[(2-chloro-4,6-difluorophenyl)amino]-4-oxo-1,2,3,4-tetrahydroquinoline-3-carboxylic acid
0.00043	-	phosphorylase a, pH 7.4, 25°C	Oryctolagus cuniculus	4-([[(2-chloro-4,5-difluorophenyl)carbonyl]carbamoyl]amino)-3-(trifluoromethoxy)benzoic acid
0.000915	-	phosphorylase b, pH 7.4, 25°C	Oryctolagus cuniculus	4-([[(2-chloro-4,5-difluorophenyl)carbonyl]carbamoyl]amino)-3-(trifluoromethoxy)benzoic acid