WebThe effect of compounds 3a–d on the ATR-dependent phosphorylation of Chk1 was evaluated by western immunoblotting, as previously published . Briefly, MCF7 cells were pretreated with 1 µM of the compounds for 30 min and exposed to 10 µM cisplatin in the presence or absence of the compounds for 8 h to induce DDR. WebApr 14, 2024 · Abstract. Ataxia telangiectasia and Rad3-related (ATR) checkpoint kinase orchestrates DNA damage response and repair pathways stimulated by replicative stresses. Recent studies have established that pharmacological inhibition of ATR is clinically promising. As M1774 is an oral ATR inhibitor in clinical development, we explored the …
Abstract LB301: Molecular pharmacology and broad synergy of …
WebOct 1, 2024 · Cisplatin with gemcitabine remains the standard up-front therapy for treatment in patients with metastatic urothelial cancer. Objective: To determine whether the use of the selective ATR inhibitor, berzosertib, could augment the activity of cisplatin with gemcitabine. Design, setting, and participants: WebJul 1, 2024 · Cisplatin first activates ATR kinase [69] which then activates p53 by phosphorylating at serine-15 [70]. p53 activates p21, Mdm2 and GADD45 genes which are responsible for cell cycle arrest and lead to apoptosis through DNA repair pathway [44]. p53 causes apoptosis directly by different mechanisms like: Degradation of FLIP (flice-like ... oy notation\u0027s
Phase 1 study of the ATR inhibitor berzosertib (formerly …
WebAug 1, 2024 · Blocking this novel pathway by inhibiting ROS, DUOXA1, ATR or Chk1 effectively overcomes cisplatin resistance in vitro and in vivo. Significantly, the clinical studies also confirm the activation of ATR and DOUXA1 in ovarian cancer patients, and elevated DOUXA1 or ATR-Chk1 pathway correlates with poor prognosis. WebSep 28, 2024 · The identification of the ATR inhibitor VE-822 as a therapeutic strategy for enhancing cisplatin chemosensitivity in esophageal squamous cell carcinoma Inducing DNA damage is known to be one of the mechanisms of cytotoxic chemotherapy agents for cancer such as cisplatin. WebMay 24, 2024 · We demonstrate that ATR is a major determinant of sensitivity to chlorambucil and cisplatin. Most likely, DNA crosslinks generated by treatment with the two drugs obstruct DNA replication, and the resulting stalled forks require ATR for their re-start and stabilisation (Zeman & Cimprich, 2014 ). oy nordic spa ltd