PD 407824

PD 407824 is a checkpoint kinase Chk1 and WEE1 inhibitor with IC50s of 47 and 97 nM, respectively. PD 407824 is a chemical BMP sensitizer and increases the sensitivity of cells to sub-threshold amounts of BMP4[1][2].

PD 407824 is sufficient to block CHK1, leading to a significant down-regulation of p21, causing activation of CDK8/9, which in turn causes depletion of SMAD2/3[1].PD 407824 is selective for Chk1 and WEE1 over PKC and Cdk4 with IC50s of 3.4 µM and 3.75 µM, respectively[3].

[1]. Palmer BD, et al. 4-Phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione inhibitors of the checkpoint kinase Wee1. Structure-activity relationships for chromophore modification and phenyl ring substitution. J Med Chem. 2006 Aug 10;49(16):4896-911. [2]. Feng L, et al. Discovery of a Small-Molecule BMP Sensitizer for Human Embryonic Stem Cell Differentiation. Cell Rep. 2016 May 31;15(9):2063-75. [3]. Smaill JB, et al. Synthesis and structure-activity relationships of N-6 substituted analogues of 9-hydroxy-4-phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-diones as inhibitors of Wee1 and Chk1 checkpointkinases. Eur J Med Chem. 2008 Jun;43(6):1276-96. Epub 2007 Aug 6.