@misc{10481/94715,
year = {2024},
month = {7},
url = {https://hdl.handle.net/10481/94715},
abstract = {NXP900 is a selective and potent SRC family kinase (SFK) inhibitor, currently being dosed in a phase 1 clinical trial, that locks SRC in the "closed" conformation, thereby inhibiting both kinase-dependent catalytic activity and kinase-independent functions. In contrast, several multi-targeted kinase inhibitors that inhibit SRC, including dasatinib and bosutinib, bind their target in the active "open" conformation, allowing SRC and other SFKs to act as a scaffold to promote tumorigenesis through non-catalytic functions. NXP900 exhibits a unique target selectivity profile with sub-nanomolar activity against SFK members over other kinases. This results in highly potent and specific SFK pathway inhibition. Here, we demonstrate that esophageal squamous cell carcinomas and head and neck squamous cell carcinomas are exquisitely sensitive to NXP900 treatment in cell culture and in vivo, and we identify a patient population that could benefit from treatment with NXP900.},
organization = {National Cancer Institute  ZIA BC 011691},
organization = {Medical Research Council Precision Medicine Doctoral Training Programme},
organization = {Nuvectis Pharma, Inc.},
publisher = {Elsevier},
keywords = {ESCC},
keywords = {HNSCC},
keywords = {Src family kinases},
title = {The SRC family kinase inhibitor NXP900 demonstrates potent antitumor activity in squamous cell carcinomas},
doi = {10.1016/j.jbc.2024.107615},
author = {Dash, Sweta and Hanson, Sabrina and King, Ben and Nyswaner, Katherine and Foss, Kelcie and Tesi, Noelle and Harvey, Mungo J.B. and Navarro Marchal, Saul Abenhamar and Woods, Alison and Poradosu, Enrique and Unciti-Broceta, Asier and Carragher, Neil O. and Brognard, John},
}