Discovery of Dinaciclib (SCH 727965): A Potent and Selective Inhibitor of Cyclin-Dependent Kinases

Area of Science:

• Oncology
• Pharmacology
• Drug Discovery

Background:

• Cyclin-dependent kinases (CDKs) are key regulators of the cell cycle.
• Dysregulation of CDKs is implicated in various cancers.
• Targeting CDKs offers a promising strategy for cancer therapy.

Purpose of the Study:

• To identify novel CDK inhibitors with a favorable balance of anti-cancer activity and tolerability.
• To utilize an in vivo screening approach for drug candidate selection.

Main Methods:

• An in vivo screening strategy was employed.
• Integrated efficacy and tolerability parameters were used to assess candidate inhibitors.
• Screening identified SCH 727965 as a potent and selective CDK inhibitor.

Main Results:

• The in vivo screening approach successfully identified a promising CDK inhibitor.
• SCH 727965 demonstrated potent inhibition of CDKs.
• SCH 727965 exhibits a suitable balance of efficacy and tolerability.

Conclusions:

• The developed in vivo screening method is effective for identifying potential oncology therapeutics.
• SCH 727965 is a potent and selective CDK inhibitor with potential for clinical development.
• SCH 727965 is currently undergoing clinical evaluation as a novel cancer treatment.