SA09-Cu is a noncompetitive and potent NDM-1 inhibitor with an IC 50 of 9.6 nM. SA09-Cu can convert NDM-1 into an inactive state by oxidizing the Zn(II)-thiolate site of the enzyme and avoids to be reduced by intracellular thiols of bacteria. SA09-Cu exhibits excellent inhibition against a series of clinical NDM-1-producing carbapenem-resistant Enterobacteriaceae (CRE) in restoring the Meropenem effect, and slows down the development of carbapenem resistance.