Although the constitutively activated break-point cluster region-Abelson (BCR-ABL) tyrosine kinase was well known to be responsible for chronic myelogenous leukemia (CML), the existence of drug-resistant mutants of BCR-ABL has made it difficult to develop effective anti-CML drugs. Here, we report the first example for a successful application of the structure-based virtual screening to identify two common inhibitors equipotent for the wild type and the most drug-resistant T315I mutant of BCR-ABL. Because both inhibitors were screened for having desirable physicochemical properties as a drug candidate and revealed micromolar inhibitory activities, they deserve consideration for further development by structure-activity relationship (SAR) studies to optimize the anti-CML activity. We also address the structural features relevant to the stabilizations of the identified inhibitors in the ATP-binding sites. The results indicate that the inhibitors should be less stabilized by the hydrogen-bond interactions with the change of the receptor from the wild type to T315I mutant due to the replacement of the hydroxy group with the ethyl moiety in the ATP-binding site. Nonetheless, the inhibitors are found to be capable of maintaining the potency for the mutant through the strengthening of hydrophobic interactions to the extent sufficient to compensate for the loss of some hydrogen bonds. This differential binding mode may serve as key information for designing new common inhibitors of the wild type and T315I mutant of BCR-ABL.