SML1761

AA-CW236

≥98% (HPLC)

• Synonym(s): 4-(2-(5-(Chloromethyl)-4-(4-(trifluoromethoxy)phenyl)-1H-1,2,3-triazol-1-yl)ethyl)-3,5-dimethylisoxazole
• Empirical Formula (Hill Notation): C₁₇H₁₆ClF₃N₄O₂
• CAS Number: 1869921-96-9
• Molecular Weight: 400.78
• UNSPSC Code: 12352200
• NACRES: NA.77
• Assay: ≥98% (HPLC)
• Form: powder

Properties

• Quality Segment: 100
• assay: ≥98% (HPLC)
• form: powder
• color: white to beige
• solubility: DMSO: 25 mg/mL protein, clear
• storage temp.: 2-8°C
• SMILES string: CC1=C(CCN2N=NC(C3=CC=C(OC(F)(F)F)C=C3)=C2CCl)C(C)=NO1
• InChI: 1S/C17H16ClF3N4O2/c1-10-14(11(2)27-23-10)7-8-25-15(9-18)16(22-24-25)12-3-5-13(6-4-12)26-17(19,20)21/h3-6H,7-9H2,1-2H3
• InChI key: MPDMMSRZEHOFPA-UHFFFAOYSA-N

Description

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).

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).

Safety Information

• Storage Class: 11 - Combustible Solids
• WGK: WGK 3
• Flash Point (°F): Not applicable
• Flash Point (°C): Not applicable