Design, synthesis and biological activity of new CDK4-specific inhibitors, based on fascaplysin.
We present the design, synthesis, and biological activity of three classes of tryptamine derivatives, which are non-planar analogues of the toxic anti-cancer agent fascaplysin. We show these compounds to be selective inhibitors of CDK4 over CDK2, the most active compound has an IC50 for the inhibition of CDK4 of 6 microM.
Aubry
Carine
C
Department of Chemistry, University of Leicester, Leicester LE1 7RH, UK. kin@le.ac.uk
Wilson
A James
AJ
Jenkins
Paul R
PR
Mahale
Sachin
S
Chaudhuri
Bhabatosh
B
Maréchal
Jean-Didier
JD
Sutcliffe
Michael J
MJ
D000595:Amino Acid Sequence; D002625:Chemistry, Organic / Q000379:methods*; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors; D051358:Cyclin-Dependent Kinase 4 / Q000037:antagonists & inhibitors*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D007211:Indoles / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D008969:Molecular Sequence Data; D015394:Molecular Structure; D014363:Tryptamines / Q000737:chemistry; D000644:Quaternary Ammonium Compounds; D002243:Carbolines; D007212:Indolizines
D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D004791:Enzyme Inhibitors; D007211:Indoles; D014363:Tryptamines; C069346:fascaplysine; D000644:Quaternary Ammonium Compounds; D002243:Carbolines; D007212:Indolizines; C030820:tryptamine