Sotorasib (Mechanism of Action)

In this article, we will discuss Sotorasib (Mechanism of Action). So, let’s get started.

Mechanism of Action

Sotorasib is an inhibitor of KRASG12C, a tumor-restricted, mutant-oncogenic form of the RAS GTPase, KRAS. Sotorasib forms an irreversible, covalent bond with the unique cysteine of KRASG12C, locking the protein in an inactive state that prevents downstream signaling without affecting wild-type KRAS. Sotorasib blocked KRAS signaling, inhibited cell growth, and promoted apoptosis only in KRAS G12C tumor cell lines. Sotorasib inhibited KRASG12C in vitro and in vivo with minimal detectable off-target activity. In mouse tumor xenograft models sotorasib-treatment led to tumor regressions and prolonged survival and was associated with anti-tumor immunity in KRAS G12C models.

Pharmacodynamics

Sotorasib exposure-response relationships and the time course of the pharmacodynamic response are unknown.

Cardiac Electrophysiology

At the approved recommended dosage, Sotorasib does not cause large mean increases in the QTc interval (> 20 msec).

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