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
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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...
متن کاملMechanism 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...
متن کاملPhase 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...
متن کاملSNS-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...
متن کاملSynergistic antitumor effects of CDK inhibitor SNS-032 and an oncolytic adenovirus co-expressing TRAIL and Smac in pancreatic cancer
Gene therapy using oncolytic adenoviruses is a novel approach for human cancer therapeutics. The current study aimed to investigate whether the combined use of an adenovirus expressing tumor necrosis factor‑related apoptosis‑inducing ligand (TRAIL) and second mitochondria‑derived activator of caspase (Smac) upon caspase activation (ZD55‑TRAIL‑IETD‑Smac) and cyclin‑dependent kinase (CDK) inhibit...
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تاریخ انتشار 2009