The TAM receptors (Tyro3, Axl, and Mertk) are a family of three homologous receptor tyrosine kinases (RTKs) that play important roles in tissue homeostasis, immune response, and the resolution of inflammation. Besides the intracellular catalytic kinase domain common to all kinases, the TAMs uniquely contain an extracellular domain that distinguishes them among all known kinases.
TAMs are overexpressed in many human cancers, thereby promoting tumor proliferation, migration, survival, and immune escape. TAM dysregulation tracks with more aggressive cancers, poorer predicted patient survival, and drug-resistant cancers. Biopharmaceutical companies are actively developing TAM‐targeting small molecule tyrosine kinase inhibitors (TKIs), as well as biologicals (mAbs), as cancer therapeutics. These conventional therapeutic approaches have serious drawbacks, such as off‐target effects and induced drug resistance.
In contrast, Rutgers scientists have discovered a novel family of small molecule inhibitors that uniquely block TAM activation by the endogenous ligand Gas6 in the extracellular domain.
These molecules include commercially available chemicals for which until now no utility has been reported as well as new chemical entities. In vitro and in vivo tests demonstrated that some of them had anti-cancer activities without discernible toxicity to normal cells. These drug candidates could represent the first of their kind in cancer therapeutics.
The subject molecules offer prospects as first-in-class drugs for cancer and other therapeutic areas.
- Greater selectivity and specificity
- Improved safety profile (fewer side effects)
- High efficiency (because they bind to an extracellular region rather than inside the tumor cell)
Intellectual Property & Development Status:
Patent pending; available for licensing and/or collaboration.