Summary of Small Molecule MYC Inhibitors for Cancer Therapy

Dr. Abdulkadir discusses the development of small molecule MYC inhibitors for cancer therapy. MYC, a well-known oncoprotein, drives human tumors by regulating various genes. Targeting MYC directly has been challenging due to its undruggable nature. Researchers have developed a compound called 361 that disrupts MYC-MAX interaction, inhibiting tumor growth and inducing immunogenic cell death, recruiting immune cells and upregulating PD-L1 to potentially enhance the response to anti-PD1 therapy. A new compound, 975, shows better tolerability and efficacy compared to 361, with a more selective impact on MYC target genes. Mechanistic studies reveal that the inhibitors preferentially affect low-affinity MYC target genes, sparing high-affinity ones, potentially explaining the therapeutic index. Ongoing studies include PK/PD analysis and formulation development to advance the compound towards clinical studies.

Innovative Approach

The innovative approach to identifying compounds targeting undruggable oncoproteins involves in silico and in vitro screening methods, as explained by Dr. Abdulkadir. Testing compounds in vivo is crucial to ensure efficacy in animals, assess potential dose-limiting toxicities, and determine dosing strategies for clinical studies. The role of the immune system in the compounds' effectiveness is highlighted, emphasizing the need for clear expectations for fellows involved in the research.

Researchers and Collaborators

Hui Hand
Mihai
Barbara
Gary Schiltz
Rama Mishra
Debu

Institutions

Northwestern University
Polsky
The Cancer Center
The New Cures Accelerator
The Prostate Cancer Foundation

Presenters

Ted Shafer

Contributors

Dr. Morgan
Dr. Abdulkadir

Notable Quotes

— 37:27 — « So then you know, even though you know when its not the initiating oncogene because this is one of the »

— 38:20 — « you have a good half-life here by ip and by oral this compound and weve done ip »

— 40:32 — « and when we look at those they are all um the pathways that are enriched »

— 43:13 — « you know why are we not shutting down all of the target genes in normal tissues and so on so »

— 44:39 — « so maybe this could actually provide a mechanistic rationale for kind of what we are seeing so um we have done a lot of »