1H-Benzimidazole-6-carboxamide, 1-ethyl-2-(hydroxydiphenylmethyl)-N-[(2R)-2-hydroxypropyl]-

VY-3-135 is a potent, orally active, and stable ACSS2 inhibitor with an IC50 value of 44 nM. VY-3-135 is specific to ACSS2 among the AcCoA synthetase family of enzymes. VY-3-135 does not inhibit ACSS1 or ACSS3 enzymatic activity. VY-3-135 can be used for the research of breast cancer[1]. VY-3-135 (0.1, 1 μM; for 24 hours) blocks acetate dependent labeling of palmitate by 13C2-acetate in ACSS2low A7C11 and ACSS2high Brpkp110 cells[1]. VY-3-135 (100 mg/kg/day; PO; 30 days) represses MDA-MB-468 (ACSS2high) tumor growth but is mostly ineffective at blocking WHIM12 (ACSS2low) growth[1].

[1]. Katelyn D Miller, et al. Targeting ACSS2 with a Transition-State Mimetic Inhibits Triple-Negative Breast Cancer Growth. Cancer Res. 2021 Mar 1;81(5):1252-1264.