| Size | Price | |
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| 100mg | ||
| 250mg | ||
| 500mg |
| ln Vitro |
In BaF3-JAK3M511I, U937, parental cells, JAK3-IN-13 (compound 12n) (10 μM; 72 hours) exhibited antiproliferative action [1]. The activities of JAK3-IN-13, with IC50 values of 177.7, 134.2, 22.9, and 1.2 nM, respectively, inhibit those of TEL-JNK1, TEL-JNK2, JNK3M511I, and JNK3. In a dose-dependent manner, JAK3-IN-13 inhibition (0-800 nM; 0-24 hours) decreases the expression of phosphorylated JAK3, STAT3, and STAT5. In G0/G1 phase, JAK3-IN-13 inhibition (0-330 nM; 24 hours) causes cell cycle arrest and, in a concentration-dependent manner, downregulates cyclin-dependent kinase 2 (CDK2), CDK4, CDK6, cyclin B1, cyclin Expression of D3, and cyclin E1 [1].
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| ln Vivo |
JAK3-IN-13 (5 mg/kg intravenously; 15 mg/kg orally) demonstrates good PK characteristics with an oral bioavailability of 20.66% [1]. JAK3-IN-13 (12.5, 25, 50 mg/kg; oral; twice daily for 10 days) exhibits anticancer activity and suppresses phosphorylated JAK3, STAT3, STAT5, CDK2, CDK4, CDK6, cyclins B1, cyclin D3, and cyclin E1[1]. Pharmacokinetic characteristics of JAK3-IN-13 in male Sprague-Dawley rats [1]. 12n iv(5 mg/kg) po(15 mg/kg) Animal number 3 3 T1/2 (h) 0.91 0.98 Cmax (ng/mL) 911.33 238.28 AUC(0-∞) (h·ng/mL) 536.99 333.50 CL (mL/min/kg) 155.22 F % 20.66 Male Sprague-Dawley rats, 5 mg/kg iv (5% DMSO + 10% solutol + 85% saline); 15 mg/kg po (0.5% HPMC in water) [ 1]
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| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: BaF3-JAK3M511I, U937, Parental, COLO-205, H1299, HCT-116, MDA-MB-231, AGS, HL 7702 Cell Tested Concentrations: 10 μM Incubation Duration: 72 hrs (hours) Experimental Results: Displayed Anti-proliferative activity, the IC50 of BaF3-JAK3M511I, U937, and parental cells are 22.9, 20.2, and 165.1 nM respectively, and the IC50 of COLO-205, H1299, and HCT-116 are >10, >10, >10, >10, >10, 3.27 μM, respectively for MDA-MB-231, AGS, and HL 7702 cells. Western Blot Analysis[1] Cell Types: U937 Cell Tested Concentrations: 0-800 nM Incubation Duration: 0-24 h Experimental Results: Dose-dependent inhibition of phosphorylation of JAK3, STAT3 and STAT5, with near-complete inhibition achieved at 200 nM. Cell cycle analysis [1] Cell Types: U937 Cell Tested Concentrations: 0-330 nM Incubation Duration: 24 hrs (hours) Experimental Results: Induced cell cycle arrest in G0/G1 phase, and down-regulated the expression of cyclin-dependent kinase 2 (CDK2) and CDK4 , CDK6, cyclin B1, cyclin D3 and cyclin E1 in a concentration-dependent manner. |
| Animal Protocol |
Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rat [1]
Doses: 5 mg/kg intravenously (iv) (iv)(iv); oral 15 mg/kg Route of Administration: intravenous (iv) (iv)injection or oral Experimental Results:Demonstrated good PK characteristics, oral bioavailability is 20.66%. Animal/Disease Models: Male CB17-SCID mouse (U937 mouse xenograft model) [1] Doses: 12.5, 25, 50 mg/kg Route of Administration: Po; twice (two times) daily for 10 days (10 mg/kg; i.p. Injection; one time/day) Experimental Results: dose-dependently inhibited the growth of U937 tumors and Dramatically inhibited the expression of phosphorylated JAK3, STAT3 and STAT5 and cell cycle-related proteins. |
| References |
[1]. Li S, et al. Discovery of Hexahydrofuro[3,2-b]furans as New Kinase-Selective and Orally Bioavailable JAK3 Inhibitors for the Treatment of Leukemia Harboring a JAK3 Activating Mutant. J Med Chem. 2022 Jul 20.
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| Molecular Formula |
C25H33CLN6O5
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|---|---|
| Molecular Weight |
533.02
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| CAS # |
2803329-86-2
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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 | 1.8761 mL | 9.3805 mL | 18.7610 mL | |
| 5 mM | 0.3752 mL | 1.8761 mL | 3.7522 mL | |
| 10 mM | 0.1876 mL | 0.9381 mL | 1.8761 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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