GSK2636771 [2-methyl-1-(2-methyl-3-(trifluoromethyl)benzyl)-6-morpholino-1H-benzo[d]imidazole-4-carboxylic acid] is a potent, orally bioavailable and selective nanomolar inhibitor of
the beta isoform of the 110 kDa catalytic subunit of class IA phosphoinositide-3
kinases (PI3K). GSK2636771 was more selective for PI3Kβ relative to other PI3K
class I enzymes (IC50: PI3Kβ = 0.89 nM) with greater than 900-fold
selectivity over PI3Kα/PI3Kγ and more than 10-fold over PI3Kδ. It inhibits AKT
phosphorylation and downstream signalling measured as decrease of PRAS40-, GSK3β-,
and RPS6-phosphorylation in PTEN mutant cell lines [1].
The activity of GSK2636771 is as follows:
1. Arkenau, H. -T.; et. al. Abstract 2514: A phase I/II, first-in-human dose-escalation study of GSK2636771 in patients (pts) with PTEN-deficient advanced tumors. J Clin Oncol 2014, 32, (suppl).
2. Qu, J.; et. al. Benzimidazole derivatives as pi3 kinase inhibitors. WO2012047538A1 (For synthesis and activity see Example 31)
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| GSK2636771: 2D and 3D Structure |
The activity of GSK2636771 is as follows:
IC50 (PI3Kβ enzyme assay) = 0.89 nM
References:
Common Name: GSK2636771
Synonyms: GSK2636771; GSK-2636771; GSK 2636771
IUPAC Name: 2-methyl-1-(2-methyl-3-(trifluoromethyl)benzyl)-6-morpholino-1H-benzo[d]imidazole-4-carboxylic
acid
CAS Number: 1372540-25-4
Mechanism of Action: Kinase Inhibitor; PI3K Inhibitor; PI3Kbeta
Inhibitor
Indication: Various Cancers; Anti-Tumor Agents
Development Stage: Phase I/II
Company: GlaxoSmithKline
Company: GlaxoSmithKline
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| 1H NMR (Estimated) for GSK2626771 |
1. Arkenau, H. -T.; et. al. Abstract 2514: A phase I/II, first-in-human dose-escalation study of GSK2636771 in patients (pts) with PTEN-deficient advanced tumors. J Clin Oncol 2014, 32, (suppl).
2. Qu, J.; et. al. Benzimidazole derivatives as pi3 kinase inhibitors. WO2012047538A1 (For synthesis and activity see Example 31)
