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...

Descripción completa

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
_version_ 1783704687341469696
author Shen, Tao
Hu, Xueqing
Liu, Xuan
Subbiah, Vivek
Mooers, Blaine H. M.
Wu, Jie
author_facet Shen, Tao
Hu, Xueqing
Liu, Xuan
Subbiah, Vivek
Mooers, Blaine H. M.
Wu, Jie
author_sort Shen, Tao
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8184971
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-81849712021-06-11 The L730V/I RET roof mutations display different activities toward pralsetinib and selpercatinib Shen, Tao Hu, Xueqing Liu, Xuan Subbiah, Vivek Mooers, Blaine H. M. Wu, Jie NPJ Precis Oncol Brief Communication 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. Nature Publishing Group UK 2021-06-07 /pmc/articles/PMC8184971/ /pubmed/34099825 http://dx.doi.org/10.1038/s41698-021-00188-x Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Brief Communication
Shen, Tao
Hu, Xueqing
Liu, Xuan
Subbiah, Vivek
Mooers, Blaine H. M.
Wu, Jie
The L730V/I RET roof mutations display different activities toward pralsetinib and selpercatinib
title The L730V/I RET roof mutations display different activities toward pralsetinib and selpercatinib
title_full The L730V/I RET roof mutations display different activities toward pralsetinib and selpercatinib
title_fullStr The L730V/I RET roof mutations display different activities toward pralsetinib and selpercatinib
title_full_unstemmed The L730V/I RET roof mutations display different activities toward pralsetinib and selpercatinib
title_short The L730V/I RET roof mutations display different activities toward pralsetinib and selpercatinib
title_sort l730v/i ret roof mutations display different activities toward pralsetinib and selpercatinib
topic Brief Communication
url 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
work_keys_str_mv AT shentao thel730viretroofmutationsdisplaydifferentactivitiestowardpralsetinibandselpercatinib
AT huxueqing thel730viretroofmutationsdisplaydifferentactivitiestowardpralsetinibandselpercatinib
AT liuxuan thel730viretroofmutationsdisplaydifferentactivitiestowardpralsetinibandselpercatinib
AT subbiahvivek thel730viretroofmutationsdisplaydifferentactivitiestowardpralsetinibandselpercatinib
AT mooersblainehm thel730viretroofmutationsdisplaydifferentactivitiestowardpralsetinibandselpercatinib
AT wujie thel730viretroofmutationsdisplaydifferentactivitiestowardpralsetinibandselpercatinib
AT shentao l730viretroofmutationsdisplaydifferentactivitiestowardpralsetinibandselpercatinib
AT huxueqing l730viretroofmutationsdisplaydifferentactivitiestowardpralsetinibandselpercatinib
AT liuxuan l730viretroofmutationsdisplaydifferentactivitiestowardpralsetinibandselpercatinib
AT subbiahvivek l730viretroofmutationsdisplaydifferentactivitiestowardpralsetinibandselpercatinib
AT mooersblainehm l730viretroofmutationsdisplaydifferentactivitiestowardpralsetinibandselpercatinib
AT wujie l730viretroofmutationsdisplaydifferentactivitiestowardpralsetinibandselpercatinib

Ejemplares similares