JANEX-1JAK3 inhibitor CAS# 202475-60-3 |
- CYT387 sulfate salt
Catalog No.:BCC1506
CAS No.:1056636-06-6
- Baricitinib phosphate
Catalog No.:BCC1401
CAS No.:1187595-84-1
- JAK2 Inhibitor V, Z3
Catalog No.:BCC1667
CAS No.:195371-52-9
- Bardoxolone methyl
Catalog No.:BCC1400
CAS No.:218600-53-4
- Ruxolitinib (INCB018424)
Catalog No.:BCC1276
CAS No.:941678-49-5
Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
| Cas No. | 202475-60-3 | SDF | Download SDF |
| PubChem ID | 3794 | Appearance | Powder |
| Formula | C16H15N3O3 | M.Wt | 297.31 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Synonyms | WHI-P131 | ||
| Solubility | DMSO : ≥ 100 mg/mL (336.35 mM) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | 4-[(6,7-dimethoxyquinazolin-4-yl)amino]phenol | ||
| SMILES | COC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC=C(C=C3)O)OC | ||
| Standard InChIKey | HOZUXBLMYUPGPZ-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C16H15N3O3/c1-21-14-7-12-13(8-15(14)22-2)17-9-18-16(12)19-10-3-5-11(20)6-4-10/h3-9,20H,1-2H3,(H,17,18,19) | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
||
| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
||
| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | JANEX-1 is a potent and specific JAK3 inhibitor (estimated Ki=2.3 μM). JANEX-1 (WHI-P131) shows potent JAK3-inhibitory activity (IC50 of 78 μM), does not inhibit JAK1 and JAK2.In Vitro:JANEX-1 (WHI-P131) shows potent JAK3-inhibitory activity (IC50 of 78 μM), does not inhibit JAK1 and JAK2, the ZAP/SYK family tyrosine kinase SYK, the TEC family tyrosine kinase BTK, the SRC family tyrosine kinase LYN, or the receptor family tyrosine kinase insulin receptor kinase, even at concentrations as high as 350 μM. JANEX-1 induces apoptosis in JAK3-expressing human leukemia cell lines NALM-6 and LC1;19 but not in melanoma (M24-MET) or squamous carcinoma (SQ20B) cells. WHI-P131 inhibits the clonogenic growth of JAK3-positive leukemia cell lines DAUDI, RAMOS, LC1;19, NALM-6, MOLT-3, and HL-60 (but not JAK3-negative BT-20 breast cancer, M24-MET melanoma, or SQ20B squamous carcinoma cell lines) in a concentration-dependent fashion. WHI-P131 inhibits clonogenic growth in a concentration-dependent fashion with EC50s of 24.4 μM for NALM-6 cells and 18.8 μM for DAUDI cells. At 100 μM, WHI-P131 inhibits the in vitro colony formation by these leukemia cell lines by >99%. In contrast, JANEX-1 does not inhibit the clonogenic growth of JAK3-negative M24-MET melanoma or SQ20B squamous carcinoma cell lines[1].In Vivo:JANEX-1 is administered at doses ranging from 5 to 100 mg/kg. Evaluation of CPK activity revealed a dose-response curve with an effective dose 50 (ED50) value of 7.44 mg/kg. Mice receiving JANEX-1 displayed significantly reduced CPK and LDH levels. In addition, the infarct size of JANEX-1-treated mice (30.16±2.79%) is significantly decreased when compared with I/R-operated mice (65.64±3.76%)[2]. JANEX-1 (WHI-P131) is absorbed rapidly, and the time to reach the maximum plasma JANEX-1 concentration (tmax) is 24.7±1.7 min. JANEX-1 is rapidly eliminated with an elimination half-life of 45.6±5.5 min. Although the predicted maximum plasma JANEX-1 concentration is 10.5 ± 0.8 μM, which is only half of the Cmax following i.v. administration of the same bolus dose, the i.p. bioavailability is 94.6% and the systemic exposure levels (i.e., AUC) are very similar to those observed after i.v. injection (17.1±2.2 μM•h versus 18.1±1.2 μM•h)[3]. References: | |||||
JANEX-1 Dilution Calculator
JANEX-1 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 3.3635 mL | 16.8175 mL | 33.6349 mL | 67.2699 mL | 84.0873 mL |
| 5 mM | 0.6727 mL | 3.3635 mL | 6.727 mL | 13.454 mL | 16.8175 mL |
| 10 mM | 0.3363 mL | 1.6817 mL | 3.3635 mL | 6.727 mL | 8.4087 mL |
| 50 mM | 0.0673 mL | 0.3363 mL | 0.6727 mL | 1.3454 mL | 1.6817 mL |
| 100 mM | 0.0336 mL | 0.1682 mL | 0.3363 mL | 0.6727 mL | 0.8409 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
Calcutta University
University of Minnesota
University of Maryland School of Medicine
University of Illinois at Chicago
The Ohio State University
University of Zurich
Harvard University
Colorado State University
Auburn University
Yale University
Worcester Polytechnic Institute
Washington State University
Stanford University
University of Leipzig
Universidade da Beira Interior
The Institute of Cancer Research
Heidelberg University
University of Amsterdam
University of Auckland
TsingHua University
The University of Michigan
Miami University
DRURY University
Jilin University
Fudan University
Wuhan University
Sun Yat-sen University
Universite de Paris
Deemed University
Auckland University
The University of Tokyo
Korea University
Janex-1 is an ATP-competitive and specific inhibitor of JAK3 with IC50 value of 78 μM [1].
Janus kinase 3 (JAK3) is a tyrosine kinase which belongs to the Janus kinase family. It is associated with the type I cytokine receptors that use common gamma chain, and provides enzymatic activity to the receptor. When ligands bind to the receptor, the conformational change of the receptor will activate the JAK3 and thus initiate downstream signaling. JAK3 interacts with actin-binding protein villin, and subsequently promote cytoskeletal remodeling and mucosal wound repair.
When tested with human lymphoblastoid B-cell line, Janex-1 showed significant inhibitory effect on JAK3 activity, but do not affect other types of tyrosine kinases, including Janus family tyrosine kinase JAK1 and JAK2, the ZAP/SYK family tyrosine kinase SYK, the TEC family tyrosine kinase BTK, the SRC family tyrosine kinase LYN. It suggested Janex-1 was highly specific to JAK3 inhibition [1]. Pretreated mouse islet with Janex-1 showed resistance to cytokine toxicity, i.e. the decreased NO synthase (iNOS) expression and thereby the nitric oxide (NO) production and subsequent islet damage. The molecular mechanism was considered that Janex-1 inhibit iNOS expression via inhibit JAK3 and other signaling transduction [2].
In NOD mouse model of type 1 diabetes, 60% of control mice became diabetic after 25 weeks. However, injection of Janex-1 (100 mg/kg/day) from week 10 to week 25 resulted in only 9% mice became diabetic. Because type 1 diabetes was caused by JAK3 and downstream signaling, the suppression of diabetes onset suggested the inhibition of JAK3 by Janex-1 [3].
References:
[1] Sudbeck E A et al. , Structure-based Design of Specific Inhibitors of Janus Kinase 3 as Apoptosis-inducing Antileukemic Agents. Clinical cancer research. 2007, 5: 1569-1582.
[2] Lv N et al. , JANEX-1, a JAK3 inhibitor, protects pancreatic islets from cytokine toxicity through downregulation of NF-¦ÊB activation and the JAK/STAT pathway. Experimental cell research. 2009, 315 (12): 2064-2071.
[3] Cetkovic-Cvrlje M et al. , Targeting JAK3 with JANEX-1 for prevention of autoimmune type 1 diabetes in NOD mice. Clinical immunology. 2003, 106: 213-225.
- Glomeratose A
Catalog No.:BCN8400
CAS No.:202471-84-9
- Ro 04-6790
Catalog No.:BCC7512
CAS No.:202466-68-0
- AM 281
Catalog No.:BCC6944
CAS No.:202463-68-1
- 1,3,7-Trihydroxy-2-prenylxanthone
Catalog No.:BCN4886
CAS No.:20245-39-0
- Hydroxygenkwanin
Catalog No.:BCN4885
CAS No.:20243-59-8
- Etoricoxib
Catalog No.:BCC1565
CAS No.:202409-33-4
- 2,2-Bis(4-chloroformyloxyphenyl)propane
Catalog No.:BCC8491
CAS No.:2024-88-6
- Scillascilloside B-1
Catalog No.:BCN6998
CAS No.:2023822-41-3
- Scillascillone
Catalog No.:BCN6992
CAS No.:2023822-40-2
- Scillascillol
Catalog No.:BCN7008
CAS No.:2023822-39-9
- PNU-159682
Catalog No.:BCC5463
CAS No.:202350-68-3
- Dasycarpol
Catalog No.:BCN7134
CAS No.:202343-57-5
- 13(18)-Oleanen-3-one
Catalog No.:BCN4887
CAS No.:20248-08-2
- 13-O-Ethylpiptocarphol
Catalog No.:BCN7448
CAS No.:202522-40-5
- OTX-015
Catalog No.:BCC1829
CAS No.:202590-98-5
- Calyxin H
Catalog No.:BCN4888
CAS No.:202596-22-3
- H-Valinol
Catalog No.:BCC2696
CAS No.:2026-48-4
- Ginkgolic acid C13:0
Catalog No.:BCN5333
CAS No.:20261-38-5
- DL-AP3
Catalog No.:BCC2459
CAS No.:20263-06-3
- DL-AP4
Catalog No.:BCC6548
CAS No.:20263-07-4
- JHW 007 hydrochloride
Catalog No.:BCC7923
CAS No.:202645-74-7
- 3α-Bis-(4-fluorophenyl) methoxytropane hydrochloride
Catalog No.:BCC6846
CAS No.:202646-03-5
- Nicotinamide N-oxide
Catalog No.:BCN1969
CAS No.:1986-81-8
- Forsythenside A
Catalog No.:BCN6440
CAS No.:202721-09-3
Targeting mast cells in endometriosis with janus kinase 3 inhibitor, JANEX-1.[Pubmed:17631002]
Am J Reprod Immunol. 2007 Aug;58(2):75-97.
Endometriosis (EMS) is a chronic inflammatory disease of multifactorial etiology characterized by implantation and growth of endometrial glands and stroma outside the uterine cavity. EMS is a significant public health issue as it affects 15-20% of women in their reproductive age. Clinical symptoms may include pelvic pain, dysmenorrhea, dyspareunia, pelvic/abdominal masses, and infertility. Symptomatic treatments such as surgical resection and/or hormonal suppression of ovarian function and analgesics are not as effective as desired. Consequently, there is an enormous unmet need to develop effective medical therapy capable of preventing the occurrence and recurrence of EMS without undesirable side-effects. EMS-associated intra-abdominal bleeding episodes, local inflammation, adhesions, and i.p. immunologic dysfunction leads to pelvic nociception and pelvic pain. Increasing evidence supports the involvement of allergic-type inflammation in EMS. Invasion of mast cells, degranulation, and proliferation of interstitial component are observed in endometriotic lesions. Presence of activated and degranulating mast cells within the nerve structures can contribute to the development of pain and hyperalgesia by direct effects on primary nociceptive neurons. Therefore, treatments targeting endometrial mast cells may prove effective in preventing or alleviating EMS-associated symptoms. The Janus kinase 3 (JAK3) is abundantly expressed in mast cells and is required for the full expression of high-affinity IgE receptor-mediated mast cell inflammatory sequelae. JANEX-1/WHI-P131 is a rationally designed novel JAK3 inhibitor with potent anti-inflammatory activity in several cellular and in vivo animal models of inflammation, including mouse models of peritonitis, colitis, cellulitis, sunburn, and airway inflammation with favorable toxicity and pharmacokinetic profile. We hypothesize that JAK3 inhibitors, especially JANEX-1, may prove useful to prevent or alleviate the symptoms of EMS.
JANEX-1, a JAK3 inhibitor, protects pancreatic islets from cytokine toxicity through downregulation of NF-kappaB activation and the JAK/STAT pathway.[Pubmed:19414010]
Exp Cell Res. 2009 Jul 15;315(12):2064-71.
JANEX-1/WHI-P131, a selective Janus kinase 3 (JAK3) inhibitor, has been shown to delay the onset of diabetes in the NOD mouse model. However, the molecular mechanism by which JANEX-1 protects pancreatic beta-cells is unknown. In the current study, we investigated the role of JANEX-1 on interleukin (IL)-1beta and interferon (IFN)-gamma-induced beta-cell damage using isolated islets. JANEX-1-pretreated islets showed resistance to cytokine toxicity, namely suppressed nitric oxide (NO) production, reduced inducible form of NO synthase (iNOS) expression, and decreased islet destruction. The molecular mechanism by which JANEX-1 inhibits iNOS expression was mediated through suppression of the nuclear factor kappaB (NF-kappaB) and JAK/signal transducer and activator of transcription (STAT) pathways. Islets treated with the cytokines downregulated the protein levels of suppressor of cytokine signaling (SOCS)-1 and SOCS-3, but pretreatment with JANEX-1 attenuated these decreases. Additionally, islets from JAK3(-/-) mice were more resistant to cytokine toxicity than islets from control mice. These results demonstrate that JANEX-1 protects beta-cells from cytokine toxicity through suppression of the NF-kappaB and JAK/STAT pathways and upregulation of SOCS proteins, suggesting that JANEX-1 may be used to preserve functional beta-cell mass.
Anti-inflammatory activity profile of JANEX-1 in preclinical animal models.[Pubmed:18024136]
Bioorg Med Chem. 2008 Feb 1;16(3):1287-98.
We examined the biologic activity of the rationally designed JAK3 inhibitor, JANEX-1, in several cellular and animal models of inflammation. Notably, JANEX-1 exhibited potent anti-inflammatory activity in each of these preclinical models, including mouse models of peritonitis, colitis, cellulitis, and systemic inflammatory response syndrome. Therefore, JANEX-1 may prove useful as a broad-spectrum anti-inflammatory agent. The present study may provide the basis for new and effective treatment as well as prevention programs for inflammatory disorders.
Janex-1, a JAK3 inhibitor, ameliorates tumor necrosis factor-alpha-induced expression of cell adhesion molecules and improves myocardial vascular permeability in endotoxemic mice.[Pubmed:22344597]
Int J Mol Med. 2012 May;29(5):864-70.
Vascular endothelial cells play an important role in leukocyte trafficking during the inflammatory process. Proinflammatory cytokines activate the expression of cell adhesion molecules in endothelial cells. Janus kinase (JAK) and signal transducer and activator of transcription (STAT) are important intracellular cytokine signaling molecules that are involved in immune responses. The purpose of this study was to investigate the effect of JAK3 inhibition on the expression of tumor necrosis factor (TNF)-alpha-induced cell adhesion molecules in vascular endothelial cells and to evaluate the therapeutic potential of JAK3 for myocardial vascular permeability in endotoxemic mice. A JAK3 inhibitor, JANEX-1, decreased the TNF-alpha-induced expression of intercellular adhesion molecule (ICAM)-1, VCAM (vascular cell adhesion molecule)-1 and fractalkine in human umbilical vein endothelial cells (HUVECs). The downregulation of the expression of these cell adhesion molecules by JANEX-1 was mediated via suppression of STAT3 phosphorylation and nuclear factor-kappaB (NF-kappaB) activation. In endotoxemic mice, pretreatment with JANEX-1 prevented not only an increase in the cardiac ICAM-1 expression by LPS in the arteriolar and capillary endothelial cells, but also myocardial vascular leakage. These results suggest that inhibition of the JAK/STAT pathway by JANEX-1 ameliorates the expression of TNF-alpha-induced cell adhesion molecules in HUVECs and improves myocardial vascular permeability.
