vamotinib (PF-114)

The introduction of imatinib in the early 2000s revolutionized CML treatment, transforming a fatal disease into a chronic condition with near-normal life expectancy for most patients...Emerging therapies such as vamotinib, KF1601, and combination regimens are being explored. Furthermore, new insights into non-kinase functions of BCR::ABL1 and the role of microRNAs in resistance open additional therapeutic avenues. This review provides a concise overview of CML from a historical and molecular perspective, highlighting diagnostic advances, evolving response criteria, and future directions in treatment.

2 of 5 subjects failing ponatinib achieved a CHR. Vamotinib dose for further phase-3 study is 300 mg/d.

Selective inhibitors of Bcr-Abl (prototype – imatinib mesylate, IM, Gleevec®) cause a therapeutic effect in the treatment of the primary process...Senexin B (SenB) and SNX631 were used for selective inhibition of CDK8/19, to suppress Bcr-Abl – IM, dasatinib, nilotinib, PF-114.Results and DiscussionsIt was found that CDK8/19 inhibition by SenB alone does not have an antiproliferative effect on CML cells...These changes were not demonstrated in KU812, where neither SenB sensitization, nor changes in expression of CKIs and c-Myc level were detected.ConclusionInhibition of CDK8/19 helps to overcome the delay of the cell cycle caused by the Bcr-Abl antagonist in CML cells and increase the death of tumor cells. The absence of general toxicity of CDK8/19 inhibitors during prolonged treatment under experimental conditions allows us to recommend CDK8/19 inhibition with targeted therapy of Bcr-Abl-positive tumors in prospect.