865317-32-4

CP681301 is a potent CDK5 inhibitor. CP681301 shows antiproliferative activity. CP681301 decreases the expression of CD133, OLIG2, SOX2, KI67, pCDK5 protein level in GSCs (Glioma stem cells). CP681301 reduces self-renewal in mouse glioma xenografts. CP681301 shows anti-tumor activity in Drosophila[1].

CP-681301 is a potentATP-competitive cyclin-dependent kinase Cdk5 inhibitor (Ki = 13.7 nM; 2.8-/40-fold selectivity over Cdk2/GSK-3β) th at blocks Cdk5 substrates phosphorylation in cultures (tau pS235 IC50 = 513 nM in CHO p25/CDK5/tau transfectants; IC50 ~500 nM against 48-h 10 μM oligomeric Aβ42-stimulated APP pT668 in murine embryonic neurons) and reverses the upregulated tau pS235 level in Cdk5 activator p25-overexpressing transgenic neonatal mice in vivo (5.8 mg/kg s.c.; 6 hrs). CP-681301 selectively inhibits Cdk5-dependent proliferation of human medullary thyroid carcinoma (MTC)but not normal human fibroblasts in cultures (5 μM48 hrs).

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[1] Mukherjee S, et al. CDK5 Inhibition Resolves PKA/cAMP-Independent Activation of CREB1 Signaling in Glioma Stem Cells. Cell Rep. 2018 May 8;23(6):1651-1664. DOI:10.1016/j.celrep.2018.04.016