A computational examination of the therapeutic advantages of fourth-generation ALK inhibitors TPX-0131 and repotrectinib over third-generation lorlatinib for NSCLC with ALK F1174C/L/V mutations.

ABSTRACT: Background: In non-small-cell lung cancer (NSCLC), a pivotal factor in promoting cancer development is the rearrangement in the anaplastic lymphoma kinase ALK gene, resulting in elevated ALK protein expression. F1174C/L/V is the acquired secondary resistant mutation in ALK. Significant survival improvements have been seen while tyrosine kinase inhibitors specifically target ALK. Nevertheless, the emergence of drug resistance hinders the clinical effectiveness of these drugs. Objective: This research sought to find the binding affinity/inhibitory effects of the existing drug lorlatinib (LOR) and upcoming TPX-0131 (zotizalkib/TPX) and repotrectinib (TPX-0005/REP) inhibitors against ALK F1174C/L/V mutations using computational approaches to identify potential strategies o

SUBMITTER: Balasundaram A 

PROVIDER: S-EPMC10808363 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature