Latest perspectives of orally bioavailable 2,4-diarylaminopyrimidine analogues (DAAPalogues) as anaplastic lymphoma kinase inhibitors: discovery and clinical developments.

ABSTRACT: The course of anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) therapy has improved impressively. The Food and Drug Administration (FDA) has approved crizotinib (Xalkori, Pfizer) as a first-in-class tyrosine kinase inhibitor (TKI) that demonstrated a substantial objective response rate (ORR) and remarkable progression-free survival (PFS). However, acquired resistance to crizotinib is still a major concern especially as the central nervous system (CNS) remains the most common sites of relapse. To combat disease resistance, limited PFS and poor CNS exposure exhibited by crizotinib (Xalkori, Pfizer) led to the discovery of numerous next generation ALK-TKIs and surprisingly most of them are 2,4-Diarylaminopyrimidine Analogues (DAAPalogues). To date, DAAPalogues ha

SUBMITTER: Latif M 

PROVIDER: S-EPMC9080316 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature