Taletrectinib (DS-6051b) free base is a potent, orally active, and next-generation selective ROS1/NTRK inhibitor. Taletrectinib free base potently inhibits recombinant ROS1, NTRK1, NTRK2, and NTRK3 with IC 50 s of 0.207, 0.622, 2.28, and 0.98 nM, respectively. Taletrectinib free base also inhibits ROS1 G2032R and other Crizotinib-resistant ROS1 mutants.

The IC 50 of Taletrectinib free base (1-1000 nM; 72 hours) against Ba/F3-TPM3-NTRK1, Ba/F3-ETV6-NTRK1, -NTRK2, -NTRK3, or KM12 cells is ~3-20?nM[1]. Taletrectinib free base (0.001-1000 nM; 2 hours) dose dependently inhibited autophosphorylation of ROS1 in U-118-MG cells in vitro[1]. Taletrectinib (DS-6051b) free base potently inhibits autophosphorylation of ROS1 in JFCR-165, JFCR-168, and MGH193-1B cells[1]. Taletrectinib free base partially suppresses phospho-NTRK1 at 10?nM, and completely suppresses by 100?nM. Taletrectinib free base potently inhibits recombinant ROS1, NTRK1, and NTRK3 in sub-nanomolar concentration in an ATP-competitive manner. Taletrectinib free base almost completely inhibits ACK, ALK, DDR1, and LTK at 0.2?μM among 160 kinases in the presence of 1 mM ATP, but did not inhibit other 152 kinases strongly[1]. Taletrectinib free base effectively inhibits Crizotinib-resistant ROS1 secondary mutations, including G2032R solvent front mutation[1]. Cell Viability Assay[1]Cell Line: TPM3-NTRK1-induced Ba/F3 cells, KM12 cells Concentration: 1-1000 nM Incubation Time: 72?hours Result: Inhibited TPM3-NTRK1-induced Ba/F3 cells and KM12 cells viability. Western Blot Analysis[1]Cell Line: U-118 MG cells (harboring FIG-ROS1 fusion gene) Concentration: 0.001-1000 nM Incubation Time: 2?hours Result: Dose dependently inhibited autophosphorylation of ROS1 in U-118-MG cells.

Taletrectinib (DS-6051b) free base (25-200 mg/kg; p.o.; once daily for 18 days) shows antitumor activity[1]. Taletrectinib free base (6.25-200?mg/kg; p.o.; once daily for 8 days) inhibits NTRK-rearranged cancer in Balb-c nu/nu mice bearing KM12 cells[1]. Taletrectinib free base (3-100 mg/kg; p.o.; once daily for 4 days) shows rapid tumor regression in the wild-type (WT) and the G2032R-mutant Ba/F3-bearing mice without severe body weight loss[1]. Animal Model: Balb-c nu/nu mice (bearing U-118 MG cells)[1]Dosage: 25, 50, 100, and 200?mg/kg Administration: P.o.; once daily for 18 days Result: Effectively inhibited tumor growth at ≥25?mg/kg without significant body weight loss.

1505514-27-1

C23H24FN5O

405.477

Taletrectinib free base;AB-106freebase;DS-6051b free base;Taletrectinib free base

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years