| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
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| ln Vitro |
The half-life of taletrectinib (1-1000 nM; 72 hours) against Ba/F3-TPM3-NTRK1, Ba/F3-ETV6-NTRK1, -NTRK2, -NTRK3, or KM12 cells is approximately 3–20 nM [1]. In U-118-MG cells, taletrectinib (0.001-1000 nM; 2 hours) dose-dependently inhibits ROS1 autophosphorylation [1]. ROS1 autophosphorylation in JFCR-165, JFCR-168, and MGH193-1B cells is efficiently inhibited by taletrectinib [1]. Phosphorylated NTRK1 is somewhat inhibited by taletrectinib at 10 nM and totally inhibited at 100 nM. Recombinant ROS1, NTRK1, and NTRK3 are potently inhibited by taletrectinib at subnanomolar concentrations in an ATP-competitive manner. When 1 mM ATP is present, 0.2 μM taletrectinib almost totally inhibits 160 kinases, including ACK, ALK, DDR1, and LTK, but not the other 152 kinases [1]. CRISPOTINIB-resistant ROS1 secondary mutations, such as the G2032R solvent front mutation, are effectively inhibited by taletrectinib [1].
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| ln Vivo |
Taletrectinib (DS-6051b) (25 -200 mg/kg; oral; once daily for 18 days) shows anti-tumor activity[1]. Taletrectinib (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 (3-100 mg/kg; oral; once daily for 4 days) shows rapid tumor regression in wild-type (WT) and G2032R mutant Ba/F3 mice without severe weight loss[1].
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: TPM3-NTRK1-induced Ba/F3 cells, KM12 cells Tested Concentrations: 1-1000 nM Incubation Duration: 72 hrs (hours) Experimental Results: Inhibited TPM3-NTRK1-induced Ba/F3 cells and KM12 cells viability. Western Blot Analysis[1] Cell Types: U-118 MG cells (harboring FIG-ROS1 fusion gene) Tested Concentrations: 0.001-1000 nM Incubation Duration: 2 hrs (hours) Experimental Results: Dose dependently inhibited autophosphorylation of ROS1 in U-118-MG cells. |
| Animal Protocol |
Animal/Disease Models: Balb-c nu/nu (nude) mice (bearing U-118 MG cells)[1]
Doses: 25, 50, 100, and 200 mg/kg Route of Administration: Po; one time/day for 18 days Experimental Results: Effectively inhibited tumor growth at ≥25 mg/kg without significant body weight loss. |
| References |
[1]. Katayama R, et al. The new-generation selective ROS1/NTRK inhibitor DS-6051b overcomes crizotinib resistant ROS1-G2032R mutation in preclinical models. Nat Commun. 2019;10(1):3604. Published 2019 Aug 9.
[2]. Fujiwara Y, et al. Safety and pharmacokinetics of DS-6051b in Japanese patients with non-small cell lung cancer harboring ROS1 fusions: a phase I study. Oncotarget. 2018;9(34):23729-23737. Published 2018 May 4. |
| Molecular Formula |
C29H34FN5O5
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|---|---|
| Molecular Weight |
551.61
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| CAS # |
1505515-69-4
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| Related CAS # |
Taletrectinib free base;1505514-27-1
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| SMILES |
FC1=CC=CC(=C1)[C@@H](C)NC1C=CC2=NC=C(C3C=CC(=CC=3)OC[C@@H](C)N)N2N=1.OC(CCCCC(=O)O)=O
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 50 mg/mL (90.64 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.77 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.77 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (3.77 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8129 mL | 9.0644 mL | 18.1288 mL | |
| 5 mM | 0.3626 mL | 1.8129 mL | 3.6258 mL | |
| 10 mM | 0.1813 mL | 0.9064 mL | 1.8129 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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