TY - JOUR
T1 - CA224, a non-planar analogue of fascaplysin, inhibits Cdk4 but not Cdk2 and arrests cells at G0/G1 inhibiting pRB phosphorylation
AU - Mahale, Sachin
AU - Aubry, Carine
AU - James Wilson, A.
AU - Jenkins, Paul R.
AU - Maréchal, Jean Didier
AU - Sutcliffe, Michael J.
AU - Chaudhuri, Bhabatosh
N1 - Funding Information:
The work in the authors’ laboratory was supported by Cancer Research, UK.
PY - 2006/8/15
Y1 - 2006/8/15
N2 - 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.
AB - 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.
KW - Cell cycle
KW - Cell growth inhibition
KW - Cyclin-dependent kinases
KW - DNA intercalation
KW - G/G arrest
KW - pRB
UR - http://www.scopus.com/inward/record.url?scp=33745727153&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2006.05.065
DO - 10.1016/j.bmcl.2006.05.065
M3 - Article
AN - SCOPUS:33745727153
SN - 0960-894X
VL - 16
SP - 4272
EP - 4278
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 16
ER -
