Definition

An orally bioavailable inhibitor of the class I phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) catalytic subunit alpha (PIK3CA), with potential antineoplastic activity. Upon oral administration, PI3K-alpha inhibitor JS105 selectively targets, binds to and inhibits PIK3CA in the PI3K/Akt (protein kinase B)/mammalian target of rapamycin (mTOR) pathway. This results in apoptosis and growth inhibition in PIK3CA-expressing tumor cells. By specifically targeting PIK3CA, JS105 may be more efficacious and less toxic than pan-PI3K inhibitors. Dysregulation of the PI3K/Akt/mTOR pathway is often found in solid tumors and results in the promotion of tumor cell growth, survival, and resistance to chemo- and radio-therapy. PIK3CA, one of the most frequently mutated oncogenes, encodes the p110-alpha catalytic subunit of the class I PI3K.