抑制肿瘤蛋白激酶BCR-ABL的激酶抑制剂的设计，是治疗慢性髓细胞白血病（CML）的一种前途光明的范例。然而，首个FDA批准的治疗CML的靶向疗法伊马替尼的疗效受到耐药性的限制。在此，我们报道了2-甲氧基苯基脲基苯并噻唑类AK-HW-90（2b）的发现，作为强效的泛BCR-ABL抑制剂，对伊马替尼抵抗突变体特别是T315I具有抑制作用。基于我们之前报道的苯并噻唑类化合物AKE-5l，设计了一个简洁的六个化合物2a-f以改善其对BCR-ABLT315I的抑制活性。将AKE-5l的6-氧吡啶酰胺基团替换为邻甲氧基苯基，并用苯基代替丙基间隔，得到2a和AK-HW-90（2b），对BCR-ABLT315I的IC50值分别为2.0和0.65 nM。在多种癌细胞中（NCI），包括白血病K-562，AK-HW-90表现出比伊马替尼更优异的抗癌活性。所得结果表明，AK-HW-90是治疗CML和其他类型癌症的一个有前途的候选药物。

The design of kinase inhibitors targeting the oncogenic kinase BCR-ABL constitutes a promising paradigm for treating chronic myeloid leukaemia (CML). Nevertheless, the efficacy of imatinib, the first FDA-approved targeted therapy for CML, is curbed by the emergence of resistance. Herein, we report the identification of the 2-methoxyphenyl ureidobenzothiazole AK-HW-90 (2b) as a potent pan-BCR-ABL inhibitor against imatinib-resistant mutants, particularly T315I. A concise array of six compounds 2a-f was designed based on our previously reported benzothiazole lead AKE-5l to improve its BCR-ABLT315I inhibitory activity. Replacing the 6-oxypicolinamide moiety of AKE-5l with o-methoxyphenyl and changing the propyl spacer with phenyl afforded 2a and AK-HW-90 (2b) with IC50 values of 2.0 and 0.65 nM against BCR-ABLT315I, respectively. AK-HW-90 showed superior anticancer potency to imatinib against multiple cancer cells (NCI), including leukaemia K-562. The obtained outcomes offer AK-HW-90 as a promising candidate for the treatment of CML and other types of cancer.