Size | Price | |
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100mg | ||
250mg | ||
500mg | ||
Other Sizes |
Targets |
TrkA 2.9 nM (IC50) TrkA TrkC
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ln Vitro |
With IC50s of 2.9, 1.1, 0.7, 0.8, 0.8, and 0.2 nM for TRKA, TRKAG595R, TRKAG667C, TRKAF589L, TRKCG623R, and TRKCG696A, respectively, TIY-7 (compound 12c) exhibits enzyme inhibitory activity[1]. With an inhibitory rate of 62%, 99%, and 11% for ALK, ROS1, and JAK1 kinase, TIY-7 (1 µM) exhibits selectivity[1].
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ln Vivo |
TIY-7 (5 mg/kg for po; 1 mg/kg for iv) shows good oral bioavailability (F) of 39.8%[1]. TIY-7 (30 mg/kg; Po; twice daily for 12-14 consecutive days) inhibits tumor progression in a dose-dependent manner in xenograft model[1]. Pharmacokinetic Parameters of TIY-7 in Male Sprague-Dawley rats[1]. Dose (mg/kg) Cmax (ng/mL) Tmax (h) T1/2 (h) CL (mL/min/kg) F % MRT0-t (h) AUCtot (ng/mL·h) AUCextra (%) ip mice 9.103 2078 0.0833 0.8 154 86 0.7 982.3 1.3 iv mice 0.711 322.7 0.0833 1.1 133 0.9 88.8 15.2 iv dog 26.76 272 (µg/mL) 0.0833 3.8 0.69 3.8 654.7 (µg/mL·h) 0.9 Male Sprague-Dawley rats; 5 mg/kg for po; 1 mg/kg for iv[1].
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Animal Protocol |
Animal/Disease Models: Male SD (Sprague-Dawley) rats[1]
Doses: 5 mg/kg for po; 1 mg/kg for iv Route of Administration: Po or iv Experimental Results: demonstrated good PK properties with an oral bioavailability (F) of 39.8%. Animal/Disease Models: 6weeks old BALB/cA nude mice (BaF3-TMP3-TRKA-WT and BaF3-ETV6-TRKC-G623R xenograft models)[1] Doses: 30 mg/kg (dissolved in 70% PEG400 and 30% water) Route of Administration: Po; twice (two times) daily; 12-14 days Experimental Results: Dose-dependently inhibited tumor progression with the TGI of 95% and 86% in BaF3-TMP3-TRKA-WT and BaF3-ETV6-TRKC-G623R xenograft model. |
References |
[1]. Mei LC,et al. Conformational adjustment overcomes multiple drug-resistance mutants of tropomyosin receptor kinase. Eur J Med Chem. 2022 Apr 25;237:114406.
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Molecular Formula |
C21H18F4N6O
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Molecular Weight |
446.40
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CAS # |
2846435-83-2
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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 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.) |
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Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.2401 mL | 11.2007 mL | 22.4014 mL | |
5 mM | 0.4480 mL | 2.2401 mL | 4.4803 mL | |
10 mM | 0.2240 mL | 1.1201 mL | 2.2401 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.