MTX-531 is an oral drug that inhibits EGFR (with an IC50 of 14.7 nM) and PI3K (with IC50 values of 6.4, 233, 8.3, and 1.1 nM for PI3Kα, PI3Kβ, PI3Kγ, and PI3Kδ respectively), and it has anti-tumor effects. It also acts as a weak agonist of PPARγ, with an IC50 of 2.5 μM, helping to alleviate hyperglycemia induced by PI3K inhibitors.
- Shows a concentration-dependent inhibitory effect on EGFR, P13K, and mTOR in CAL-33 cells.
- Activates PPARγ in 3T3-L1 cells.
- Inhibits EGFR and PI3K-mTOR pathway signaling in a time-dependent manner in mice.
- Suppresses tumor proliferation in mice.
- Shows excellent tolerance in mice and uniquely does not cause the hyperglycemia commonly seen with PI3K inhibitors.
- Enhances MEK inhibition in CRC.
- Combined with KRAS-G12C inhibitors, it suppresses tumor growth in mice with KRAS-G12C mutant colorectal cancer or pancreatic tumors.