GSK864

Names

[ Name ]:
GSK864

[Synonym ]:
1H-Pyrazolo[4,3-c]pyridine-3,7-dicarboxamide, 1-[(4-fluorophenyl)methyl]-4,5,6,7-tetrahydro-N3-(4-methoxy-3,5-dimethylphenyl)-7-methyl-5-(1H-pyrrol-2-ylcarbonyl)-, (7S)-
GSK864
(7S)-1-(4-Fluorobenzyl)-N3-(4-methoxy-3,5-dimethylphenyl)-7-methyl-5-(1H-pyrrol-2-ylcarbonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-3,7-dicarboxamide

Biological Activity

[Description]:

GSK864 is an isocitrate dehydrogenase 1 (IDH1) mutant inhibitor; inhibits IDH1 mutants R132C, R132H, and R132G with IC50 values of 8.8, 15.2 and 16.6 nM.

[Related Catalog]:

Signaling Pathways >> Metabolic Enzyme/Protease >> Isocitrate Dehydrogenase (IDH)

Research Areas >> Cancer

[Target]

IC50: 8.8 nM (IDH1 mutants R132C), 15.2 nM (IDH1 mutants R132H), 16.6 nM (IDH1 mutants R132G)[1]

[In Vitro]

GSK864 inhibits 2-HG production in R132C IDH1 mutant HT1080 fibrosarcoma cells with an EC50 of 320 nM by LCMS/MS analysis[1].

[In Vivo]

Following intraperitoneal (IP) administration in CD-1 mice, significant concentrations of GSK864 are maintained in peripheral blood samples of mice for up to 24 hours. Analysis of BM cells for expression of markers of early differentiation reveals slightly increased numbers of huCD45+ CD38+ cells in R132C or R132H IDH1 mutant engrafted mice treated with GSK864[1].

[Animal admin]

Mice: Mice receive GSK864 (213 mg/kg, 10 mL/kg) via intraperitoneal (ip) administration. IP formulation is PG:DMSO:PEG400:H2O (16.7:3.3:40:40). Serial blood samples (~0.030 mL) are collected via the femoral artery catheter at 15, 30, 45, 60, 120, 180 min following administration[1].

[References]

[1]. Okoye-Okafor UC, et al. New IDH1 mutant inhibitors for treatment of acute myeloid leukemia. Nat Chem Biol. 2015 Nov;11(11):878-86.

[Related Small Molecules]

AG-120 | Enasidenib | AGI-5198 | Vorasidenib (AG-881) | AGI-6780 | IDH-305 | BAY-1436032 | Mutant IDH1 inhibitor | Mutant IDH1-IN-1 | Mutant IDH1-IN-2 | Olutasidenib

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Boiling Point ]:
782.9±60.0 °C at 760 mmHg

[ Molecular Formula ]:
C₃₀H₃₁FN₆O₄

[ Molecular Weight ]:
558.603

[ Flash Point ]:
427.3±32.9 °C

[ Exact Mass ]:
558.239075

[ LogP ]:
0.01

[ Vapour Pressure ]:
0.0±2.7 mmHg at 25°C

[ Index of Refraction ]:
1.661

[ Storage condition ]:
2-8℃