Taletrectinib free base (AB-106 free base) is a novel potent, selective and orally active ROS1/NTRK inhibitor.Taletrectinib free base has potent inhibitory effects on recombinant ROS1, NTRK1, NTRK2, and NTRK3, with IC50s of 0.207, 0.622, 2.28 and 0.98 nM, respectively, Taletrectinib free base also inhibited ROS1 G2032R and other Crizotinib-resistant ROS1 mutations.

Taletrectinib free base (1-1000 nM; 72 h) has an IC50 of ~3 -20 nM against Ba/F3-TPM3-NTRK1, Ba/F3-ETV6-NTRK1, -NTRK2, -NTRK3, or KM12 cells.[1]
Taletrectinib free base (0.001-1000 nM; 2 h) dose-dependently inhibits ROS1 autophosphorylation in U-118-MG cells in vitro.[1]
Taletrectinib free base potently inhibits ROS1 autophosphorylation in JFCR-165, JFCR-168 and MGH193-1B cells.[1]
Taletrectinib free base partially inhibits phosphorylated NTRK1 at 10 nM and completely inhibits it at 100 nM. Taletrectinib free base potently inhibits recombinant ROS1, NTRK1, and NTRK3 in an ATP-competitive manner at subnanomolar concentrations. Taletrectinib free base at 0.2 μM almost completely inhibits ACK, ALK, DDR1, and LTK among the 160 kinases but does not strongly inhibit the other 152 kinases in the presence of 1 mM ATP.[1]
Taletrectinib free base effectively inhibits crizotinib-resistant ROS1 secondary mutations, including the G2032R solvent front mutation.[1]

Taletrectinib free base (DS-6051b) (25 -200 mg/kg; oral; once daily for 18 days; Balb-c nu/nu mice bearing U-118 MG cells) shows anti-tumor activity.[1]
Taletrectinib free base (6.25 -200 mg/kg; oral; once daily for 8 days;) inhibits NTRK-rearranged cancer in Balb-c nu/nu mice harboring KM12 cells.[1]
Taletrectinib free base (3-100 mg/kg; p.o.; once daily for 4 days) shows rapid tumor regression in wild-type (WT) and G2032R mutant Ba/F3-carrying mice without severe weight loss.[1]