KEAP1 mutant NSCLC exhibits resistance to conventional therapeutic approaches, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy [39]. We also confirmed that KEAP1-deficient cells were evidently resistant to the MEK inhibitor MEK162 and the chemotherapy drug CPT (Fig.S2G). Curren...
For instance, the pharmacologic targeting of the KEAP1/NFE2L2 pathway is actively pursued,9 and the glutaminase inhibitor telaglenastat is undergoing clinical investigations in KEAP1/NFE2L2-mutant LUAD in association with chemotherapy plus pembrolizumab (KEAPSAKE trial, available at https://clinical...
inhibiting the Keap1-Nrf2 PPI can be an effective strategy for triggering Nrf2 to regulate oxidative stress. Structure-based virtual screening was performed to discover a potentially novel Keap1-Nrf2 PPI inhibitor wherein KCB-F06 was identified. The inhibitory effects of KCB-F06 on osteoclastogenesis...
www.nature.com/scientificreports OPEN received: 16 December 2015 accepted: 04 May 2016 Published: 24 May 2016 An inhibitor of the Keap1-Nrf2 protein-protein interaction protects NCM460 colonic cells and alleviates experimental colitis Meng-Chen Lu1,2, Jian-Ai Ji1,2,Yong-Lin Jiang1,2,...
While there is a NRF2-activation in Barrett’s esophagus and EAC, so far, no clinical relevant NRF2-inhibitor is available [30]. Inflammation is involved in the progression of Barrett’s esophagus and especially in EAC by an increased TNFα and TNFR1 signature [31]. NFκB was shown to ...
and probableble clinical translation [142,149]. It has been discovered that certain medications now in use to treat a wide range of disorders inhibit Nrf2 function. All-trans-retinoic acid (ATRA) has been proposed as a specific Nrf2 inhibitor, as it prevents Nrf2 from forming a complex with...
Camptothecin, a chemotherapeutic DNA topoisomerase inhibitor, can suppress Nrf2 activity in hepatocellular carcinoma cells and sensitize them to chemotherapies (Chen et al., 2017). Camptothecin is an anticancer drug approved to treat a broad spectrum of cancers, inhibition of Nrf2 could be one of ...
absence of the Nrf2 inhibitor, ML-385. (f) mRNA abundance of NQO1 and IL6 from PPBL (n=3) and healthy MZ (n=3) B-LCLs activated with IL-21 plus CD40L in the presence or absence of the NRF2 activator, CDDO (1 μM). (g) Effect of Nrf2 inhibition using K67 on IL-6 ...
et al. Discovery of potent Keap1-Nrf2 protein-protein interaction inhibitor based on molecular binding determinants analysis. J. Med. Chem. 57, 2736–2745 (2014). CAS PubMed Google Scholar Davies, T. G. et al. Monoacidic inhibitors of the Kelch-like ECH-associated protein 1: nuclear ...
The NRF2-LacZ fusion protein is not detectable in NRF2 KO mice in unstressed conditions, but it accumulates in response to diethylmaleate (DEM, a Keap1-modifying electrophile), or MG-132 (a proteasome inhibitor) treatment [8]. A quick turnover of NRF2-LacZ indicates that KEAP1 interacts ...