Drug Discovery: Towards the Synthesis of Novel CDK2-Spy1 Inhibitors
Standing
Undergraduate
Type of Proposal
Oral Research Presentation
Faculty
Faculty of Science
Faculty Sponsor
Dr. John F. Trant
Proposal
As vital regulatory proteins in the cell cycle, cyclin-dependent kinases (CDKs) and cyclins ensure normal cell division and growth by monitoring check points in the cell cycle. CDKs are inactive on its own, but when a cyclin binds to CDK the activated CDK-Cyclin complexes then carry out their role as cell cycle regulators. Unregulated CDK-Cyclin complexes cause cells to grow and divide at a premature stage, and that can lead to uncontrolled cell growth. Existing treatments such as CKI (cyclin-dependent kinase inhibitor) therapy have cytotoxicity issues because of their inability to differentiate cancer cells from healthy cells, resulting in unwanted side effects.
Our collaborators in the Porter Lab have identified a new target: CDK2-Spy1 complex. Spy proteins are alternative activators to CDKs in cancer cells, but not in healthy cells, making them an ideal therapeutic target. Notably, the Spy1 gene is among the top 50 genes associated with carcinoma, yet the CDK2-Spy1 complex has never been selectively targeted before in terms of CKI therapy. We therefore aim to synthesize molecules that selectively target CDK2-Spy1 complexes to develop a chemotherapy that has minimal cytotoxicity issues.
In this presentation I will discuss our current progress towards small molecule inhibitors that show promising selectivity for CDK2-Spy1 complexes based on computational studies. Our synthetic routes and the analytical techniques employed to characterise these compounds will be described.
Availability
I am available every day from 12-3pm for Mar 29 -- Apr 1.
Drug Discovery: Towards the Synthesis of Novel CDK2-Spy1 Inhibitors
As vital regulatory proteins in the cell cycle, cyclin-dependent kinases (CDKs) and cyclins ensure normal cell division and growth by monitoring check points in the cell cycle. CDKs are inactive on its own, but when a cyclin binds to CDK the activated CDK-Cyclin complexes then carry out their role as cell cycle regulators. Unregulated CDK-Cyclin complexes cause cells to grow and divide at a premature stage, and that can lead to uncontrolled cell growth. Existing treatments such as CKI (cyclin-dependent kinase inhibitor) therapy have cytotoxicity issues because of their inability to differentiate cancer cells from healthy cells, resulting in unwanted side effects.
Our collaborators in the Porter Lab have identified a new target: CDK2-Spy1 complex. Spy proteins are alternative activators to CDKs in cancer cells, but not in healthy cells, making them an ideal therapeutic target. Notably, the Spy1 gene is among the top 50 genes associated with carcinoma, yet the CDK2-Spy1 complex has never been selectively targeted before in terms of CKI therapy. We therefore aim to synthesize molecules that selectively target CDK2-Spy1 complexes to develop a chemotherapy that has minimal cytotoxicity issues.
In this presentation I will discuss our current progress towards small molecule inhibitors that show promising selectivity for CDK2-Spy1 complexes based on computational studies. Our synthetic routes and the analytical techniques employed to characterise these compounds will be described.