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.
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Authors | Sachin Mahale, Carine Aubry, A James Wilson, Paul R Jenkins, Jean-Didier Maréchal, Michael J Sutcliffe, Bhabatosh Chaudhuri |
Journal | Bioorganic & medicinal chemistry letters
(Bioorg Med Chem Lett)
Vol. 16
Issue 16
Pg. 4272-8
(Aug 15 2006)
ISSN: 0960-894X [Print] England |
PMID | 16750360
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Biphenyl Compounds
- CA 224
- Indoles
- Retinoblastoma Protein
- fascaplysine
- DNA
- Cyclin-Dependent Kinase 2
- Cyclin-Dependent Kinase 4
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Topics |
- Antineoplastic Agents
(pharmacology)
- Biphenyl Compounds
(chemical synthesis, pharmacology)
- Chemistry, Pharmaceutical
- Cyclin-Dependent Kinase 2
(metabolism)
- Cyclin-Dependent Kinase 4
(metabolism)
- DNA
(chemistry)
- Drug Design
- G1 Phase
- Indoles
(chemical synthesis, chemistry, pharmacology)
- Inhibitory Concentration 50
- Models, Chemical
- Phosphorylation
- Resting Phase, Cell Cycle
- Retinoblastoma Protein
(metabolism)
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