Small-molecule cyclin-dependent kinase modulators

High Throughput Screens Yield Small Molecule Inhibitors of Leishmania CRK3:CYC6 Cyclin-Dependent Kinase

BACKGROUND Leishmania species are parasitic protozoa that have a tightly controlled cell cycle, regulated by cyclin-dependent kinases (CDKs). Cdc2-related kinase 3 (CRK3), an essential CDK in Leishmania and functional orthologue of human CDK1, can form an active protein kinase complex with Leishmania cyclins CYCA and CYC6. Here we describe the identification and synthesis of specific small mole...

Successful treatment of animal models of rheumatoid arthritis with small-molecule cyclin-dependent kinase inhibitors.

Intraarticular gene transfer of cyclin-dependent kinase (CDK) inhibitors to suppress synovial cell cycling has shown efficacy in treating animal models of rheumatoid arthritis. Endogenous CDK inhibitors also modulate immune function via a CDK-independent pathway. Accordingly, systemic administration of small molecules that inhibit CDK may or may not ameliorate arthritis. To address this issue, ...

Cyclin-Dependent Kinase Inhibitors Rheumatoid Arthritis with Small-Molecule Successful Treatment of Animal Models of

Small molecule modulators of antioxidant response pathway.

Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor that regulates Antioxidant Response Element (ARE)-mediated transcription of a plethora of antioxidant and protective genes to counteract the harmful effects of reactive oxygen species or environmental carcinogens. Studies have demonstrated that pre-emptive activation of the Nrf2-ARE pathway reinforces the cellular defense mecha...

RESPONSE: re: preclinical and clinical development of cyclin-dependent kinase modulators

In the last decade, the discovery and cloning of the cyclin-dependent kinases (cdks), key regulators of cell cycle progression, have led to the identification of novel modulators of cdk activity. Initial experimental results demonstrated that these cdk modulators are able to block cell cycle progression, induce apoptotic cell death, promote differentiation, inhibit angiogenesis, and modulate tr...