Pralsetinib

Pralsetinib is a Kinase Inhibitor. The mechanism of action of pralsetinib is as a Rearranged during Transfection (RET) Inhibitor.|Pralsetinib is an orally bioavailable selective inhibitor of mutant forms of and fusion products involving the proto-oncogene receptor tyrosine kinase RET, with potential antineoplastic activity. Upon administration, pralsetinib binds to and targets various RET mutants and RET-containing fusion product. RET gene mutations and translocations result in the upregulation and/or activation of RET tyrosine kinase activity in various cancer cell types; dysregulation of RET activity plays a key role in the development and regression of these cancers.
Pralsetinib is a potent, selective RET inhibitor, and was optimized from a hit compound identified from a compound library that included more than 60 chemical scaffolds. However, as of 2020, detailed medicinal chemistry on the optimization process has yet to be published. Pralsetinib proved to be more potent and selective than cabozantinib or vandertanib against both wild-type and abnormal RET. The agent also showed a level of selectivity against RET relative to VEGFR2, whereas previous agents showed very little selectivity. On September 4, 2020, the Food and Drug Administration granted accelerated approval to pralsetinib (GAVRETO®, Blueprint Medicines Corporation) for adult patients with metastatic RET fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA-approved test.
Class: receptor tyrosine kinase; Treatment: RET-altered lung, thyroid cancers; Other name: BLU-667; Elimination half-life = 22 h; Protein binding = 97%