Taletrectinib (DS-6051b) free base 是一种有效的口服活性下一代选择性ROS1/NTRK抑制剂。Taletrectinib free base 分别以0.207、0.622、2.28 和 0.98 nM 的IC50对重组 ROS1、NTRK1、NTRK2 和 NTRK3 有较强的抑制作用。Taletrectinib free base还抑制 ROS1 G2032R 和其他抗 Crizotinib 的 ROS1 突变体。
| 生物活性 | Taletrectinib (DS-6051b) free base is a potent, orally active, and next-generation selectiveROS1/NTRKinhibitor. Taletrectinib free base potently inhibits recombinant ROS1, NTRK1, NTRK2, and NTRK3 withIC50s 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[1][2]. |
体外研究
(In Vitro) | The IC50of 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. |
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体内研究
(In Vivo) | 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. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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