Zeteletinib (BOS-172738; DS-5010) is a highly potent and selective orally active inhibitor of the RET kinase, demonstrating nanomolar potency against RET and over 300-fold selectivity against VEGFR2. It exhibits remarkable efficacy against wild-type RET, RET V804M/L gatekeeper mutants, and the frequently occurring oncogenic RET mutation M918T, with potent antitumor activity.

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

In a Ba/F3-RET subcutaneous tumor model, Zeteletinib (BOS-172738; DS-5010) administered at 10 mg/kg twice daily (bid) effectively induces tumor regression[1]. Similarly, in an LC2/ad NSCLC xenograft model harboring the RET-CCDC6 fusion gene, Zeteletinib at 1 mg/kg three times daily (tid) induces tumor regression[1].