| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
ROS1/NTRK
|
|---|---|
| ln Vitro |
Taletrectinib free base (1-1000 nM; 72 hours) has an IC50 of approximately 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 hours) dose-dependently inhibits ROS1 autophosphorylation in U-118-MG cells in vitro [1]. Taletrectinib (DS-6051b) free base effectively inhibits ROS1 autophosphorylation in JFCR-165, JFCR-168 and MGH193-1B cells [1]. Taletrectinib free base partially inhibits phospho-NTRK1 at 10 nM and completely inhibits it at 100 nM. Taletrectinib free base potently inhibits recombinant ROS1, NTRK1, and NTRK3 at subnanomolar concentrations in an ATP-competitive manner. In the presence of 1 mM ATP, 0.2 μM Taletrectinib free base almost completely inhibits 160 kinases in ACK, ALK, DDR1 and LTK, but does n
|
| ln Vivo |
Taletrectinib (DS-6051b) free base (25-200 mg/kg; oral; once daily for 18 days) showed anti-tumor efficacy [1]. Taletrectinib free base (6.25-200 mg/kg; oral; once daily for 8 days) suppresses NTRK-rearranged cancer in Balb-c nu/nu mice harboring KM12 cells [1]. Taletrectinib free base (3-100 mg/kg; oral; once daily for 4 days) showed rapid tumor regression in wild-type (WT) and G2032R mutant Ba/F3 mice without considerable weight loss [1] .
|
| Enzyme Assay |
Kinase selectivity profiling[1]
An off-chip mobility shift assay was performed. The effect of DS-6051b at a concentration of 200 nM on 160 kinases was evaluated in the presence of 1 mM ATP and expressed as % inhibition. Inhibitory activities of DS-6051b on ACK, ALK, DDR1, DDR2, KIT, LTK, ROS1, NTRK1, NTRK2, NTRK3, and TXK were determined by the mobility shift assay. ATP concentration in the assay was set at the approximate Km value of each kinase for ATP or 1 mM. The IC50 values were estimated according to the four-parameter logistic model. |
| Cell Assay |
Cell viability assay [1]
Cell Types: Ba/F3 cells and KM12 cells induced by TPM3-NTRK1 Tested Concentrations: 1-1000 nM Incubation Duration: 72 hrs (hours) Experimental Results: Inhibition of the viability of Ba/F3 cells and KM12 cells induced by TPM3-NTRK1. Western Blot Analysis[1] Cell Types: U-118 MG cells (with Fig-ROS1 fusion gene) Tested Concentrations: 0.001-1000 nM Incubation Duration: 2 hrs (hours) Experimental Results: Dose-dependent inhibition of ROS1 itself in U-118-MG cells Phosphorylation. |
| Animal Protocol |
Animal/Disease Models: Balb-c nu/nu (nude) mice (carrying U-118 MG cells) [1]
Doses: 25, 50, 100 and 200 mg/kg Route of Administration: Oral; one time/day for 18 days Experimental Results: ≥ 25 mg/kg can effectively inhibit tumor growth without significant weight loss. |
| References |
|
| Additional Infomation |
Taletrectinib is an orally available inhibitor of the receptor tyrosine kinases C-ros oncogene 1 (ROS1) and the neurotrophic tyrosine receptor kinase (NTRK) types 1, 2 and 3, with potential antineoplastic activity. Upon oral administration, taletrectinib binds to and inhibits ROS1 and the NTRK family members. This inhibition leads to a disruption of ROS1- and NTRK-mediated signaling and eventually inhibits the growth of tumor cells that are overexpressing ROS1 and/or NTRKs. ROS1, overexpressed in certain cancer cells, plays a key role in cell growth and survival of cancer cells. NTRK mutations or rearrangements play a key role in cancer progression.
|
| Molecular Formula |
C23H24FN5O
|
|---|---|
| Molecular Weight |
405.467967987061
|
| Exact Mass |
405.196
|
| Elemental Analysis |
C, 68.13; H, 5.97; F, 4.69; N, 17.27; O, 3.95
|
| CAS # |
1505514-27-1
|
| Related CAS # |
Taletrectinib;1505515-69-4
|
| PubChem CID |
72202474
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
3.8
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
30
|
| Complexity |
532
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
C[C@H](COC1=CC=C(C=C1)C2=CN=C3N2N=C(C=C3)N[C@H](C)C4=CC(=CC=C4)F)N
|
| InChi Key |
HEVHTYMYEMEBPX-HZPDHXFCSA-N
|
| InChi Code |
InChI=1S/C23H24FN5O/c1-15(25)14-30-20-8-6-17(7-9-20)21-13-26-23-11-10-22(28-29(21)23)27-16(2)18-4-3-5-19(24)12-18/h3-13,15-16H,14,25H2,1-2H3,(H,27,28)/t15-,16-/m1/s1
|
| Chemical Name |
3-[4-[(2R)-2-aminopropoxy]phenyl]-N-[(1R)-1-(3-fluorophenyl)ethyl]imidazo[1,2-b]pyridazin-6-amine
|
| Synonyms |
Taletrectinib free base; AB-106DS-6051b; AB106DS6051b; AB 106DS 6051b
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4663 mL | 12.3314 mL | 24.6627 mL | |
| 5 mM | 0.4933 mL | 2.4663 mL | 4.9325 mL | |
| 10 mM | 0.2466 mL | 1.2331 mL | 2.4663 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
