Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia.

Mechanism of Action of SNS-032, a Novel Cyclin Dependent Kinase Inhibitor, in Chronic Lymphocytic Leukemia Short title: Transcriptional Inhibition by SNS-032 in CLL

LYMPHOID NEOPLASIA Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia

Inhibitors of cyclin-dependent kinases (Cdks) have been reported to have activities in chronic lymphocytic leukemia cells by inhibiting Cdk7 and Cdk9, which control transcription. Here we studied the novel Cdk inhibitor SNS-032, which exhibits potent and selective inhibitory activity against Cdk2, Cdk7, and Cdk9. We hypothesized that transient inhibition of transcription by SNS-032 would decrea...

Phase I and pharmacologic study of SNS-032, a potent and selective Cdk2, 7, and 9 inhibitor, in patients with advanced chronic lymphocytic leukemia and multiple myeloma.

PURPOSE SNS-032 is a highly selective and potent inhibitor of cyclin-dependent kinases (Cdks) 2, 7, and 9, with in vitro growth inhibitory effects and ability to induce apoptosis in malignant B cells. A phase I dose-escalation study of SNS-032 was conducted to evaluate safety, pharmacokinetics, biomarkers of mechanism-based pharmacodynamic (PD) activity, and clinical efficacy. PATIENTS AND ME...

SNS-032 inhibits mTORC1/mTORC2 activity in acute myeloid leukemia cells and has synergistic activity with perifosine against Akt

BACKGROUND Acute myeloid leukemia (AML) is a heterogeneous disorder with aberrant regulation of a variety of signal pathways. Therefore, simultaneous targeting of two or even more deregulated signal transduction pathways is needed to overcome drug resistance. Previously, it was reported that SNS-032, a selective cyclin-dependent kinase inhibitor, is an effective agent for treatment of AML; howe...

Inhibition of Cyclin-dependent Kinase (CDK) Decreased Survival of NB4 Leukemic Cells: Proposing a p53-Independent Sensitivity of Leukemic Cells to Multi-CDKs Inhibitor AT7519

An unbounded number of events exist beneath the intricacy of each particular hematologic malignancy, prompting the tumor cells into an unrestrained proliferation and invasion. Aberrant expression of cyclin-dependent kinases (CDKs) is one of these events which disrupts regulation of cell cycle and subsequently, results in cancer progression. In this study, we surveyed the repressive impact of mu...