Tersolisib

**Semantic type:** Pharmacologic Substance

**Definition:** An orally bioavailable, brain penetrative, selective inhibitor of the class I phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) catalytic subunit alpha (phosphoinositide 3-kinase alpha; PIK3CA; PI3K p110alpha) mutant H1047X, with potential antineoplastic activity. Upon oral administration, tersolisib selectively targets and allosterically binds to the PIK3CA mutated form PIK3CA H1047X, thereby preventing the activity of the H1047X mutant. This prevents PIK3CA H1047X-mediated activation of the PI3K/Akt (protein kinase B)/mammalian target of rapamycin (mTOR) pathway. This results in both apoptosis and growth inhibition in PIK3CA H1047X mutant-expressing tumor cells. By specifically targeting the PIK3CA H1047X mutation, tersolisib may be more efficacious and less toxic than other PI3K-alpha inhibitors that are not mutant specific. 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. Tersolisib is able to penetrate the blood-brain-barrier (BBB).

**Synonyms:** - Mutant-selective PI3K-alpha H1047X Inhibitor STX-478 - Mutant-selective PI3Kalpha H1047X Inhibitor STX-478 - PIK3CA H1047X Mutant Inhibitor STX-478 - PIK3CA H1047X Mutation Inhibitor STX-478 - STX 478 - STX-478 - STX478 - TERSOLISIB