PI3k-alpha binding compounds and uses thereof

Abstract

Provided herein are small molecule covalent inhibitors of the PI3Kα-KRASG12C interaction which are useful as cancer therapeutics. Without wishing to be bound by theory, the compounds disclosed herein disrupt, and in certain embodiments, impede or inhibit PI3Kα-KRASG12C interaction, but cause minimal interference with the active site of PI3Kα. Existing PI3Kα inhibitors which block the active site of PI3Kα cause deleterious side effects such as hyperglycemia. In contrast, the inhibitors as disclosed disrupt PI3Kα-KRASG12C interaction and disrupt the PI3Kα / Akt pathway without causing hyperglycemia or other undesirable off-target effects.