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

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.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

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

doi

10.1016/j.bmcl.2006.05.065

subject

Has Abstract

pub_date

2006-08-15 00:00:00

pages

4272-8

issue

16

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(06)00611-1

journal_volume

16

pub_type

杂志文章

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