SNS-032 Mechanism
The progression of a cell through replication is regulated by kinases known as the cyclin-dependent kinases, or CDKs. In addition, some CDKs are responsible for turning on the process of transcription, which translates a DNA sequence encoding a protein into mRNA, the message or code that dictates how amino acids should be arranged to synthesize a protein. Some proteins are particularly important to the survival of a cancer cell, as well as its interaction with normal tissues to sustain its growth. If these survival proteins are turned off, then the pro-apoptotic proteins can act to force the cancer cell to die.
SNS-032 selectively inhibits CDK2, CDK7, and CDK9. CDK2 and CDK7 are active in cell-cycle progression. CDK7 is also active in promoting transcription, as is CDK9. SNS-032 therefore has dual mechanisms of action-inhibiting proliferation by blocking replication, and inducing apoptosis by blocking transcription to turn off survival and growth factors. With SNS-032, the cancer cells are selectively targeted both because these cells can be proliferative, and also because survival and growth factors are much more susceptible to transcriptional inhibition than the pro-apoptotic proteins. SNS-032 is in Phase 1 for the treatment of the B-lymphoid malignancies chronic lymphocytic leukemia and multiple myeloma.
