Zeteletinib hemiadipate (BOS-172738; DS-5010) is an orally active compound that functions as a selective inhibitor of RET kinase. It exhibits nanomolar potency against RET and a 300-fold selectivity towards VEGFR2. Notably, Zeteletinib hemiadipate demonstrates exceptional effectiveness against various forms of RET, including the wild type, RET V804M/L gatekeeper mutants, and the oncogenic RET mutation M918T. Additionally, Zeteletinib hemiadipate exerts potent antitumor effects.

In biochemical assays involving 106 kinases, Zeteletinib hemiadipate (BOS-172738; DS-5010) demonstrated significant inhibitory activity, surpassing 80% inhibition at 193 nM for both RET and platelet-derived growth factor receptor (PDGFR) alpha/beta. Furthermore, Zeteletinib displayed potent efficacy against RET and RET-GKm (V804L), with IC50 values in the single-digit nanomolar range, even in the presence of a high ATP concentration. Conversely, its inhibitory effect on KDR exceeded 1000 nM[1].

In biochemical assays of 106 kinases, RET and platelet-derived growth factor receptor (PDGFR) alpha/beta were inhibited by more than 80% with 193 nM Zeteletinib (BOS-172738; DS-5010) hemiadipate. The IC50 values of Zeteletinib hemiadipate against RET and RET-GKm (V804L) were single-digit nanomolar, even under high ATP conditions, while it was over 1000 nM against KDR[1].