Drugs of today
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Ponatinib is a novel, next-generation, small-molecule tyrosine kinase inhibitor with potent activity against the BCR-ABL fusion oncogene as well as all other ABL kinase domain mutations that confer resistance to earlier generation tyrosine kinase inhibitors. Due to its unique structure, it is the only tyrosine kinase inhibitor with the capability to counter the highly resistant T315I or gate-keeper mutation in leukemic cells that express the Philadelphia chromosome. This review will focus on the preclinical pharmacology, pharmacokinetics and clinical utility of ponatinib in the treatment of chronic myeloid leukemia and Philadelphia chromosome-positive adult acute lymphoblastic leukemia.
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Cystic fibrosis (CF) is a life-shortening disorder that affects over 30,000 people in the U. S. and 70,000 worldwide. CF is caused by mutations in the CFTR gene, which codes for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. ⋯ In the current review, we summarize the development and clinical experience with VX-770 (ivacaftor), a small molecule that increases CFTR chloride conductance in vitro and in vivo, including wild-type and G551D CFTR. The G551D CFTR mutation is the third most common CF disease-causing mutation, in which the CFTR protein localizes to the epithelial cell membrane but has defective gating. With restoration of adequate CFTR function through pharmacotherapy, it is possible that the clinical course of patients with CF could be markedly improved, including longevity, quality of life and treatment burden.