PIM-Targeted PROTACs
April 24, 2024 | 11:00 AM – 12:00 PM
REGISTER to attend a free NCI webinar hosted by TTC. The inventor will discuss newly developed PIM kinase-targeting PROTACs that promote the degradation of the PIM kinases in a prostate cancer cell model and increased chemo-sensitization.
Attendees will learn about a new family of Proteolysis Targeting Chimeras (PROTACS) that selectively target Proviral Integration for the Moloney murine leukemia virus (PIM) kinases which have roles in cancer development and mediating resistance to radio and chemotherapy; and is overexpressed in multiple cancers. Several small molecule PIM kinase inhibitors have had minimal effect in suppressing cancer phenotypes due to the PIM kinase inhibitors promoting intrinsic resistance. By contrast, these PIM targeted PROTACs suppress PIM kinase activity by completely degrading the PIM kinase proteins – intrinsic resistance is therefore avoided.
Presenter
John Brognard, Ph.D.
Senior Investigator
Laboratory of Cell and Developmental Signaling
Center for Cancer Research
National Cancer Institute
About the Featured Technology
PIM kinases are overexpressed in many solid cancers – including prostate, breast, colon, endometrial, gastric and pancreatic. PIM1 overexpression is predictive of poor survival in multiple cancer types. While several selective pan-PIM inhibitors were developed and tested in clinical trials, all ultimately increased PIM1-3 protein levels and developed resistance to the inhibitors. PROTACs targeting of the PIM kinases for degradation provides superior catalytic inhibition as these compounds target PIM kinases pro-tumorigenic functions, which are not linked to kinase activity. Additionally, these PROTACs prevent the onset of resistance due to increased expression of PIM kinases that occur from catalytic inhibition. They represent unique opportunities as novel anti-cancer therapies.
Competitive Advantages
- PROTACs target PIM kinases’ pro-tumorigenic functions which are not linked to kinase activity
- Prevents resistance resulting from increased PIM kinase expression due to catalytic inhibition
- PROTACs increase chemo-sensitivity
- Compared to small molecule inhibitors, PROTACs:
- show promise overcoming tumor resistance
- offer novel, rapid and reversible chemical knockout capabilities
Commercial Applications
- As a novel anti-cancer therapy to degrade PIM kinase proteins
- As a novel treatment for prostate, breast, and colon cancers, among others
- As a PIM targeting moiety for additional targeted therapeutics
Who Should Attend?
- Business development professionals
- Drug development professionals
- Biotech/pharma/academia researchers
- Investors and entrepreneurs
Why attend?
- Assess co-developing the technology
- Interact with the inventor, ask questions and provide feedback
- Learn how to partner with the NCI (or NIH)