Taletrectinib (DS-6051b) 是一种有效的口服活性下一代选择性ROS1/NTRK抑制剂。Taletrectinib 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 还抑制 ROS1 G2032R 和其他抗 Crizotinib 的 ROS1 突变体。
生物活性 | Taletrectinib (DS-6051b) is a potent, orally active, and next-generation selectiveROS1/NTRKinhibitor. Taletrectinib potently inhibits recombinant ROS1, NTRK1, NTRK2, and NTRK3 withIC50s of 0.207, 0.622, 2.28, and 0.98 nM, respectively. Taletrectinib also inhibits ROS1 G2032R and other Crizotinib-resistant ROS1 mutants[1][2]. |
体外研究 (In Vitro) | The IC50of Taletrectinib (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 (0.001-1000 nM; 2 hours) dose dependently inhibited autophosphorylation of ROS1 in U-118-MG cells in vitro[1]. Taletrectinib potently inhibits autophosphorylation of ROS1 in JFCR-165, JFCR-168, and MGH193-1B cells[1]. Taletrectinib 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 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 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) (25-200 mg/kg; p.o.; once daily for 18 days) shows antitumor activity[1]. Taletrectinib (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 (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 | 4°C, sealed storage, away from moisture *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture) |
溶解性数据 | In Vitro: DMSO : 50 mg/mL(90.64 mM;Need ultrasonic) 配制储备液 1 mM | 1.8129 mL | 9.0644 mL | 18.1287 mL | 5 mM | 0.3626 mL | 1.8129 mL | 3.6258 mL | 10 mM | 0.1813 mL | 0.9064 mL | 1.8129 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。 储备液的保存方式和期限:-80℃, 6 months; -20℃, 1 month (sealed storage, away from moisture)。-80℃ 储存时,请在 6 个月内使用,-20℃ 储存时,请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液,再依次添加助溶剂: ——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用;
以下溶剂前显示的百 分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂: 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.08 mg/mL (3.77 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (3.77 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂: 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.08 mg/mL (3.77 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (3.77 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。 3. 请依序添加每种溶剂: 10% DMSO 90%corn oil Solubility: ≥ 2.08 mg/mL (3.77 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (3.77 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例,取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。 *以上所有助溶剂都可在本网站选购。
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