The SRC family kinase inhibitor NXP900 demonstrates potent anti-tumor activity in squamous cell carcinomas.

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 (ESCC) and head and neck squamous cell carcinomas (HNSCC) 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.

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Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest AUB and NOC have received research grant funding from Nuvectis Pharma; in addition, AUB and NOC had patents to EP3298015B1, JP6684831B2, US10294227B2, CN107849050B and CA3021550A1 licensed to Nuvectis Pharma.