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

Sachin Mahale, Carine Aubry, A. James Wilson, Paul R. Jenkins, Jean Didier Maréchal, Michael J. Sutcliffe, Bhabatosh Chaudhuri

    Research output: Contribution to journalArticlepeer-review

    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 IC50 ∼ 5.5 μM). As would be expected of a Cdk4 inhibitor that does not inhibit Cdk2, it maintains a G0/G1 block in synchronised cancer cells and inhibits Cdk4-specific phosphorylation of the retinoblastoma protein. © 2006 Elsevier Ltd. All rights reserved.
    Original languageEnglish
    Pages (from-to)4272-4278
    Number of pages6
    JournalBioorganic and Medicinal Chemistry Letters
    Volume16
    Issue number16
    DOIs
    Publication statusPublished - 15 Aug 2006

    Keywords

    • Cell cycle
    • Cell growth inhibition
    • Cyclin-dependent kinases
    • DNA intercalation
    • G0/G1 arrest
    • pRB

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