Mechanism of Action: Cyclin-dependent kinase (CDK) inhibition
Indication: Solid Tumors
How this therapy can help
AT7519 is a small molecule targeted inhibitor of several CDKs that regulate two important disease processes; the cell replication cycle and gene expression. The normal regulation of the cell cycle is disrupted in all cancers allowing the uncontrolled tissue growth characteristic of the disease. CDKs 1 and 2 act as key controls of the cell cycle, and the inhibition of these enzymes both prevents cell proliferation and initiates cell death. AT7519 is an inhibitor of both CDK1 and 2 and induces tumor shrinkage in multiple animal models of cancer.
In addition to its direct effects on the cell cycle, AT7519 is also a potent inhibitor of RNA polymerase II-dependent transcription. This activity results from inhibition by AT7519 of another cyclin-dependent kinase, CDK9. The survival of several tumor types is very dependent on the cellular levels of certain anti-apoptotic proteins (e.g. Mcl-1), which require RNA polymerase II activity for their generation. This is true for hematological malignancies in particular (e.g. CLL and AML) and AT7519 has been found to induce rapid cell death in leukemia cell lines and tumor shrinkage in relevant animal models.
AT7519 is currently being investigated in a Phase 1/2 study in combination with AT13387.
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