Catalog No.: PC-25485Not For Human Use, Lab Use Only.
VVD-065 is a first-in-class, allosteric molecular glue of Keap1-Cul3 E3-ligase complex and NRF2 inhibitor, specifically and covalently engages C151 on KEAP1 with engagement potency (TE50) of 9 nM in KYSE70 cells, promotes KEAP1-CUL3 complex formation, leading to enhancement of NRF2 degradation.
VVD-065 (VVD065) is a first-in-class, allosteric molecular glue of Keap1-Cul3 E3-ligase complex and NRF2 inhibitor, specifically and covalently engages C151 on KEAP1 with engagement potency (TE50) of 9 nM in KYSE70 cells, promotes KEAP1-CUL3 complex formation, leading to enhancement of NRF2 degradation.
VVD-065 covalently binds C151 of KEAP1, may increase KEAP1 activity by stabilizing a KEAP1 conformation that favors CUL3 binding.
VVD-065 induces robust degradation of NRF2 and decreases expression of NRF2 target genes.
VVD-065 (5-25 mg/kg) exhibits cancer cell growth inhibitory effects.
VVD-065 exhibits anti-tumorigenic effects in KYSE70 tumor bearing animals.
VVD-065 exhibits strong antitumor effects in syngeneic with cisplatin and nab-paclitaxel in various solid tumor types such as NSCLC, ESCC, HNSCC, and uterine cancers.
1. Nilotpal Roy, et al. Suppression of NRF2-dependent cancer growth by a covalent allosteric molecular glue. bioRxiv, 2024, preprint, 10.1101/2024.10.04.616592.
2. Nil Roy, et al. Mol Cancer Ther (2023) 22 (12_Supplement): PR011.
