The L730V/I RET roof mutations display different activities toward pralsetinib and selpercatinib

Recently Food and Drug Administration (FDA)-approved pralsetinib (BLU-667) and selpercatinib (LOXO-292) are RET-selective protein tyrosine kinase inhibitors for treating RET-altered cancers, but whether they have distinct activity was unknown. The L730V/I mutations at the roof of the solvent-front s...

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Detalles Bibliográficos
Autores principales: Shen, Tao, Hu, Xueqing, Liu, Xuan, Subbiah, Vivek, Mooers, Blaine H. M., Wu, Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Brief Communication
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184971/
https://www.ncbi.nlm.nih.gov/pubmed/34099825
http://dx.doi.org/10.1038/s41698-021-00188-x
Descripción
Sumario:Recently Food and Drug Administration (FDA)-approved pralsetinib (BLU-667) and selpercatinib (LOXO-292) are RET-selective protein tyrosine kinase inhibitors for treating RET-altered cancers, but whether they have distinct activity was unknown. The L730V/I mutations at the roof of the solvent-front site of the RET kinase were identified as strongly resistant to pralsetinib but not to selpercatinib. Selpercatinib effectively inhibited these mutants and the KIF5B-RET(L730V/I) oncogene-driven tumors.

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