IACS-56676 is a selective NRAS G12D inhibitor with a target IC50 of 0.031 μM. IACS-56676 stabilizes the p-loop, maintains key interactions with Asp12, Gly60 and Asp69, and achieves selectivity against wild-type KRAS through substitution targeting Leu95. IACS-56676 can be used in the research of melanoma, hematologic malignancies and thyroid cancer [1].
In Vitro, IACS-56676 potently reduces viability of NRASG12D-mutant THP1 cells with an IC50 of 0.073 μM[1]. IACS-56676 has minimal CYP inhibition activity, with no measurable inhibition of CYP2D6 and CYP2C9 up to 10 μM, and weak inhibition of CYP3A4 isoforms[1].
References:
[1]. Cox JB, et al. Structure-Guided Development of NRAS G12D Inhibitors Based on a 5‑Azaindole Core. ACS Med Chem Lett. 2026;17(2):425-432. Published 2026 Jan 22.
In Vitro, IACS-56676 potently reduces viability of NRASG12D-mutant THP1 cells with an IC50 of 0.073 μM[1]. IACS-56676 has minimal CYP inhibition activity, with no measurable inhibition of CYP2D6 and CYP2C9 up to 10 μM, and weak inhibition of CYP3A4 isoforms[1].
References:
[1]. Cox JB, et al. Structure-Guided Development of NRAS G12D Inhibitors Based on a 5‑Azaindole Core. ACS Med Chem Lett. 2026;17(2):425-432. Published 2026 Jan 22.