A Novel Cyclin Dependent Kinase (CDK) Inhibitor P1446A Induces Apoptosis Of Chronic Lymphocytic Leukemia B Cells
Godbersen C, Agarwal VR, Paiva C et al.
Key Points:
P1446A, orally active compound inhibits CDK-1,-4,-6, and -9 at nanomolar concentrations. Effect of P1446A on primary B-CLL cells from 40 CLL patients and on MEC1 cell line examined.
After 2-hour incubation with P1446A at 1500nM concentration, CLL cells showed features of apoptosis (PARP cleavage).
P1446A-induced cell death did not depend upon IGHV mutational status or cytogenetic abnormalities. However, samples which carried deletion 17p showed decreased sensitivity towards the CDK inhibitor.
P1446 also induced apoptosis in MEC1 cell line after 6 hours of incubation at 1.5 μM.
Implications:
- P1446A demonstrated significant pre-clinical activity against B-CLL.
View the original abstract on the ASH website.
