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. Here, 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.
