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ID: ALA1138971

Journal: Bioorg Med Chem Lett

Title: CA224, a non-planar analogue of fascaplysin, inhibits Cdk4 but not Cdk2 and arrests cells at G0/G1 inhibiting pRB phosphorylation.

Authors: Mahale S, Aubry C, James Wilson A, Jenkins PR, Maréchal JD, Sutcliffe MJ, Chaudhuri B.

Abstract: Tryptamine derivatives, non-planar and potentially less toxic analogues of the anti-cancer agent fascaplysin, have been synthesised. They specifically inhibit Cdk4-D1 vis a vis Cdk2-A but, unlike fascaplysin, do not bind or intercalate DNA. CA224 is the most potent compound identified (Cdk4-D1 IC(50) approximately 5.5 microM). As would be expected of a Cdk4 inhibitor that does not inhibit Cdk2, it maintains a G(0)/G(1) block in synchronised cancer cells and inhibits Cdk4-specific phosphorylation of the retinoblastoma protein.

CiteXplore: 16750360

DOI: 10.1016/j.bmcl.2006.05.065