MTX-531 (MTX531) is a first-in-class, potent and selective inhibitor of EGFR and PI3K with IC50 of 15  nM and 6.4  nM (PI3Kα), respectively.
MTX-531 is exquisitely selective for HER (human EGFR) and PI3K family members, only 9 protein kinases outside of the HER family are inhibited by >80% at 10 uM in a broad panel of >400 protein and lipid kinases.
MTX-531 demonstrates concentration-dependent inhibition of EGFR, PI3K and mTOR as measured by lower levels of phosphorylated (p)EGFR, protein kinase B (Akt) and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) in CAL-33 HNSCC model.
MTX-531 (100 mg/ kg, oral daily administration) inhibits EGFR and PI3K-mTOR signaling and tumor growth in HNSCC PDX models, potentiates MEK inhibition in CRC, and is synergistic with KRAS-G12C inhibition.
MTX-531 acts as a weak agonist of PPARγ, an attribute that likely mitigates hyperglycemia induced by PI3K inhibition.