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Purity: ≥98%
JANEX-1 (aslo known as WHI-P131) is a novel, potent and selective inhibitor of the Janus kinase 3 (JAK3) that selectively inhibits JAK3 with an IC50 of 78 µM and does not inhibit JAK1 and JAK2. It triggers apoptosis in human acute lymphoblastic leukemia (ALL) cells. Following i.v. administration, the terminal elimination half-life of WHI-P131 was 73.2 min in rats, 103.4 min in mice, and 45.0 min in monkeys. The i.v. administered WHI-P131 showed a very wide tissue distribution in mice. Following i.p. administration, WHI-P131 was rapidly absorbed in both rats and mice, and the time to reach the maximum plasma concentration (tmax) was 24.8 min in rats and 10.0 min in mice.
| ln Vitro |
Even at concentrations as high as 350 μM, JANEX-1 (WHI-P131) exhibits strong inhibitory activity against JAK3 (IC50 is 78 μM), but not against JAK1 and JAK2, ZAP/SYK family tyrosine kinase SYK, TEC family tyrosine kinase BTK, SRC family tyrosine kinase Acid kinase LYN, or receptor family tyrosine kinase insulin receptor kinase. JAK3-expressing human leukemia cell lines NALM-6 and LC1;19 undergo apoptosis when exposed to JANEX-1, but not melanoma (M24-MET) or squamous cell carcinoma (SQ20B) cells. While JAK3-negative BT-20 breast cancer, M24-MET melanoma, or the SQ20B squamous carcinoma cell line are not inhibited by WHI-P131, it does so in a concentration-dependent way for the JAK3-positive leukemia cell lines DAUDI, RAMOS, LC1;19, NALM-6, MOLT-3, and HL-60. WHI-P131 has an EC50 of 24.4 μM in NALM-6 cells and 18.8 μM in DAUDI cells, which indicates that it suppresses colony formation in a concentration-dependent manner. WHI-P131 reduced several leukemia cell lines' in vitro colony formation by >99% at 100 μM. Conversely, in JAK3-negative M24-MET melanoma or SQ20B squamous carcinoma cell lines, JANEX-1 does not decrease clonogenicity [1].
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| ln Vivo |
There are several dosages of JANEX-1 that can be used: 5 to 100 mg/kg. A dose-response curve with an effective dose 50 (ED50) value of 7.44 mg/kg was found by CPK activity evaluation. The levels of CPK and LDH were significantly lowered in mice given JANEX-1. Furthermore, JANEX-1-treated animals had a considerably smaller infarct size (30.16±2.79%) than I/R-operated mice (65.64±3.76%) [2]. The absorption of JANEX-1 (WHI-P131) occurs quickly; the maximum plasma JANEX-1 concentration (tmax) is reached in 24.7±1.7 minutes. With a 45.6±5.5 minute elimination half-life, JANEX-1 is removed quickly. The systemic exposure level (i.e., AUC) was the same as after intravenous injection, despite the fact that the estimated maximum plasma JANEX-1 concentration of 10.5 ± 0.8 μM is only half the Cmax after intraperitoneal injection of the same bolus dose. The bioavailability was 94.6%. The obtained results (17.1±2.2 μM?h vs. 18.1±1.2 μM?h) were quite similar [3].
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| References |
[1]. Sudbeck EA, et al. Structure-based design of specific inhibitors of Janus kinase 3 as apoptosis-inducing antileukemic agents. Clin Cancer Res. 1999 Jun;5(6):1569-82.
[2]. Oh YB, et al. Inhibition of Janus activated kinase-3 protects against myocardial ischemia and reperfusion injury in mice. Exp Mol Med. 2013 May 17;45:e23 [3]. Uckun FM, et al. In vivo toxicity and pharmacokinetic features of the janus kinase 3 inhibitor WHI-P131 [4-(4'hydroxyphenyl)-amino-6,7- dimethoxyquinazoline. Clin Cancer Res. 1999 Oct;5(10):2954-62. [4]. Xia F, et al. IL4 (interleukin 4) induces autophagy in B cells leading to exacerbated asthma. Autophagy. 2018;14(3):450-464 |
| Molecular Formula |
C16H15N3O3
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| Molecular Weight |
297.31
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| CAS # |
202475-60-3
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| SMILES |
O(C([H])([H])[H])C1=C(C([H])=C2C(=C1[H])C(=NC([H])=N2)N([H])C1C([H])=C([H])C(=C([H])C=1[H])O[H])OC([H])([H])[H]
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.41 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 25.0 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: ≥ 2.5 mg/mL (8.41 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 25.0 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: ≥ 2.5 mg/mL (8.41 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 | 3.3635 mL | 16.8175 mL | 33.6349 mL | |
| 5 mM | 0.6727 mL | 3.3635 mL | 6.7270 mL | |
| 10 mM | 0.3363 mL | 1.6817 mL | 3.3635 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.
Measurement of myocardial injury.Exp Mol Med.2013 May 17;45:e23. |
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Effects of Janus-activated kinase 3 (JAK3) suppression on cardiomyocyte apoptosis.Exp Mol Med.2013 May 17;45:e23. |
Effects of Janus-activated kinase 3 (JAK3) suppression on infiltration of inflammatory cells.Exp Mol Med.2013 May 17;45:e23. |
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