Application

AA-CW236 has been used as an inhibitor of m6G DNA methyltransferase in mouse embryo fibroblasts.

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 µM) effectively prevents MGMT from repairing DNA damage, causing significantly more upregulated O6-alkylguanine accumulation than the pseudosubstrate inhibitor Lomeguatrib (1 µM) when co-administered with the DNA-alkylating agent Temozolomide/TMZ (300 µM) in MCF-7 cells. Likewise, AA-CW236 is shown to boost TMZ toxicity in Caco-2 cultures (IC₅₀ = 227 and 673 µM, respectively, with or without 3 µM AA-CW236 co-treatment).

Packaging

5, 25 mg in glass bottle