binding of substance 14 is partly similar to dasatinib, the aminothiazole segment of substance 14 makes a bi-dentate H-bonding interaction with the backbone CO and NH of Met-318 while the methoxy-benzene falls nicely into a hydrophobic pocket created by Val 256, Ala 253, Lys 271 and Ala 380. Whilst the similar binding properties to those of dasatinib, suggests the possibility of producing Bcr-Abl TKI's from thiazole cores is real, the question remains open whether this research will just lead to a dasatinib analog or a novel way to inhibit TKs. Others Rebastinib (DCC-2036) Also an inhibitor of TIE-2 and VEGFR-2. It has had a phase 1 clinical trial for Leukemias (Ph+ CML With T315I Mutation). It is in a phase 1 clinical trial of combination therapy for metastatic breast cancer. Asciminib (ABL001) is an inhibitor of the Abelson kinase targeting the myristoyl pocket to allosterically inhibit the enzyme. As of August 2020, it had completed a phase III study in CML (ASCEMBL) showing superior efficacy to bosutinib. Summary Current status - re Ph+ CML Imatinib remains a standard frontline TKI. Nilotinib and dasatinib are also approved by the FDA as frontline drugs, in June and October 2010, respectively. Four of these drugs, nilotinib, dasatinib, bosutinib and ponatinib are approved for the treatment of imatinib-resistant or intolerant CML. The first-line data for these compounds are encouraging and suggest that some or all of them may replace imatinib as a frontline standard TKI in the future. References Leukemia Medical treatments Non-receptor tyrosine kinase inhibitors Drug discovery