Synonyms: 4-(2-(5-(Chloromethyl)-4-(4-(trifluoromethoxy)phenyl)-1H-1,2,3-triazol-1-yl)ethyl)-3,5-dimethylisoxazole
Molecular Formula: C17H16ClF3N4O2
Molecular Weight: 400.78
Linear Structural Formula: C17H16ClF3N4O2
Purity: >=98% (HPLC)
Storage: 2-8C
Biochem Physiol Actions: AA-CW236 is a cell-permeable chloromethyl triazole (CMT) derivative that acts as a non-pseudosubstrate inhibitor against human O(6)-alkylguanine DNA methyltransferase (MGMT) by targeting MGMT active site Cys145 for covalent modification (KI = 24 nM, kinact = 0.03/min), displaying little affinity toward cysteines from other cellular proteins. AA-CW236 pretreatment (1 muM) effectively prevents MGMT from repairing DNA damage, causing significantly more upregulated O6-alkylguanine accumulation than the pseudosubstrate inhibitor Lomeguatrib (1 muM) when co-administered with the DNA-alkylating agent Temozolomide/TMZ (300 muM) in MCF-7 cells. Likewise, AA-CW236 is shown to boost TMZ toxicity in Caco-2 cultures (IC50 = 227 and 673 muM, respectively, with or without 3 muM AA-CW236 co-treatment).