Standing

Undergraduate

Type of Proposal

Oral Research Presentation

Faculty

Faculty of Science

Faculty Sponsor

Dr. John Trant

Abstract/Description of Original Work

COTI-2 is a small molecule with anticancer potential that targets p53, which is an important tumour-suppressor protein that is mutated in most cancers. It therefore cannot activate various responses, including cell-cycle arrest or apoptosis; COTI-2 allows for mutant forms of p53 to normalize to its wild-type form and this allows p53 to respond appropriately to tumour growth and cancer cells. It is currently unknown how and where COTI-2 works in the cells to restore the function to p53. In order to try to understand this, we seek to attach a handle for a tag such as biotin to COTI-2 will allow us to determine where the drug is working in the cells.

In this presentation, I will describe our progress towards the synthesis of COTI-2 derivatives with amine functional groups attached to the molecule, to which markers such as biotin can be appended. To ensure that these derivatives are adequate models for the activity of COTI-2 they will be tested using isothermal titration calorimetry to determine that their thermodynamic data is similar enough to COTI-2 itself. If this research is successful, it will clear the way for COTI-2 to further advance in the clinical approvals process and ultimately be used to treat a variety of cancers. This could also lead to the development of similar anticancer drugs and help treat cancer in combination with other treatments.

Availability

March 29 12-3, March 31 2-3, April 1 12-3

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COTI-2: A Small Molecule with Anticancer Potential

COTI-2 is a small molecule with anticancer potential that targets p53, which is an important tumour-suppressor protein that is mutated in most cancers. It therefore cannot activate various responses, including cell-cycle arrest or apoptosis; COTI-2 allows for mutant forms of p53 to normalize to its wild-type form and this allows p53 to respond appropriately to tumour growth and cancer cells. It is currently unknown how and where COTI-2 works in the cells to restore the function to p53. In order to try to understand this, we seek to attach a handle for a tag such as biotin to COTI-2 will allow us to determine where the drug is working in the cells.

In this presentation, I will describe our progress towards the synthesis of COTI-2 derivatives with amine functional groups attached to the molecule, to which markers such as biotin can be appended. To ensure that these derivatives are adequate models for the activity of COTI-2 they will be tested using isothermal titration calorimetry to determine that their thermodynamic data is similar enough to COTI-2 itself. If this research is successful, it will clear the way for COTI-2 to further advance in the clinical approvals process and ultimately be used to treat a variety of cancers. This could also lead to the development of similar anticancer drugs and help treat cancer in combination with other treatments.