pictilisib + apitolisib

**Pictilisib + apitolisib** is a combination of two small molecule inhibitors targeting the PI3K/AKT/mTOR pathway, investigated for potential synergy in cancer therapy. Pictilisib (GDC-0941) is a potent, selective oral inhibitor of class I PI3K isoforms (primarily PI3Kα/δ with IC50 of 3 nM), modestly selective against PI3Kβ and PI3Kγ, reducing pAkt phosphorylation to inhibit tumor cell proliferation and survival. Apitolisib (GDC-0980) is an oral dual inhibitor of class I PI3K isoforms and mTOR kinase, demonstrating broad preclinical antitumor activity via pathway suppression and apoptosis induction. Developed by Genentech (Roche), this pairing leverages complementary inhibition of the hyperactivated PI3K-mTOR axis common in solid tumors, though no specific combination trials are documented; individual agents reached phase II/III but faced toxicity and limited efficacy hurdles.