Eras-4001

Eras-4001 is a potent, orally active pan- KRAS inhibitor with K d values of 110, 13 and 39 pM against wild-type, G12D and G12V mutant KRAS, respectively, and exhibits selectivity toward wild-type HRAS and NRAS. Eras-4001 inhibits ERK1/2 phosphorylation and cell viability in cancer cells. Eras-4001 induces tumor growth inhibition and regression in subcutaneous xenograft models. Eras-4001 can be used in research on non-small cell lung cancer, ovarian cancer, etc. ^[1]

In Vivo, Eras-4001 (10-300 mg/kg; p.o.; twice daily for 20 days) exhibits dose-dependent activity in a KRAS G12V non-small cell lung cancer mouse model^[1]. Eras-4001 (30-300 mg/kg; p.o.; twice daily for 15 consecutive days) exhibits significant tumor regression in a mouse KRAS G12V ovarian cancer model^[1]. Eras-4001 (30-100 mg/kg; p.o.; twice daily for 30 consecutive days) exhibits significant tumor regression in a patient-derived xenograft mouse model of G12D non-small cell lung cancer^[1].

In Vitro, Eras-4001 inhibits both active and inactive KRASG12D-RAF1 RBD complex formation with single-digit nanomolar potency^[1]. Eras-4001 (3 hours) inhibits ERK phosphorylation in KRASWT and mutant cancer cell lines (AsPC-1, GP2d, MKN1, SW620, RKN, LoVo, LU99, A375), with quantified IC₅₀ values reported^[1]. Eras-4001 (4-7 days) potently inhibits 3D cell viability in KRASWT amplified cancer cell lines (IC₅₀ 0.7-9.1 nM), KRASG12X mutant cancer cell lines (IC₅₀ 0.7-56.0 nM), and KRASG13D mutant cancer cell lines (IC₅₀ 0.7-56.0 nM), and has minimal activity in KRASQ61H mutant and KRAS-independent cell lines^[1].

References:
[1]. Bae, J. H., et al. (2025). ERAS-4001 is a pan-KRAS inhibitor with robust anti-tumor activity in KRAS altered solid tumors. ERAS, 4001(5.65), 1-65.