| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
IRAK1
Interleukin-1 receptor-associated kinase 1 (IRAK1). IRAK1 is a serine/threonine kinase that plays a critical role in the signaling pathways of Toll-like receptors (TLRs) and interleukin-1 receptors (IL-1Rs). Upon receptor activation, IRAK1 is recruited to the receptor complex, where it undergoes phosphorylation and activation, leading to the downstream activation of NF-κB and MAPK pathways and the production of pro-inflammatory cytokines. JH-X-119-01 hydrochloride is a potent and selective IRAK1 inhibitor. By inhibiting IRAK1, the compound blocks TLR and IL-1R signaling, reducing the production of pro-inflammatory mediators and attenuating the inflammatory response. |
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| ln Vitro |
When Jh-X-119-01 (10 μM) is added to LPS-treated macrophages in vitro, it reduces the phosphorylation of NF-κB and the levels of mRNA for IL-6 and TNFα. IRAK1 phosphorylation is specifically inhibited by Jh-X-119-01[1].
In vitro, JH-X-119-01 hydrochloride is a potent and selective IRAK1 inhibitor. The compound effectively inhibits IRAK1 kinase activity, blocking downstream signaling through NF-κB and MAPK pathways. In cell-based assays, JH-X-119-01 hydrochloride inhibits the production of pro-inflammatory cytokines in response to TLR or IL-1R stimulation. Combining JH-X-119 with ibrutinib shows synergism in MYD88 mutated cells. |
| ln Vivo |
LPS-challenged mice who receive Jh-X-119-01 have increased survival and decreased immunopathies. Mice's survival is increased by Jh-X-119-01 at a dose of 5 mg/kg body weight. Raising the dosage to 10 mg/kg considerably improves survival[1].
In vivo, JH-X-119-01 hydrochloride ameliorates LPS-induced sepsis in mice. By inhibiting IRAK1, the compound reduces the production of pro-inflammatory cytokines and attenuates the systemic inflammatory response in sepsis models. The compound has been investigated for potential therapeutic applications in inflammatory and immune-related conditions. However, detailed in vivo efficacy data are limited in the available literature. |
| Enzyme Assay |
The in vitro enzyme/receptor binding (cell-free) assay for JH-X-119-01 hydrochloride typically involves measuring the inhibition of IRAK1 kinase activity using purified recombinant IRAK1 enzyme. The assay is performed by incubating IRAK1 with a peptide substrate and ATP in the presence of varying concentrations of the compound. The phosphorylation of the substrate is measured using a luminescent or fluorescent detection method, and the IC50 for IRAK1 inhibition is determined from dose-response curves. Selectivity assays can be performed to assess the compound's activity against other kinases.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: RAW 264.7 cells and THP-1 cells Tested Concentrations: 10 μM Incubation Duration: 15 minutes Experimental Results: diminished LPS (100 ng/mL)-induced phosphorylation of IκBα and NF-κB-P65. In vitro cellular assays for JH-X-119-01 hydrochloride are performed using cell lines that express IRAK1 and respond to TLR or IL-1R stimulation. Cells are treated with varying concentrations of JH-X-119-01 hydrochloride and stimulated with a TLR agonist (such as LPS) or IL-1β. The production of pro-inflammatory cytokines (such as TNF-α, IL-6, and IL-1β) is measured in the culture supernatant by ELISA. The inhibition of IRAK1-mediated signaling can be assessed by measuring the phosphorylation of downstream signaling molecules, such as IRAK1 itself, TAK1, or IKK. |
| Animal Protocol |
Animal/Disease Models: C57BL/6 (20-22 g, male) mice[1]
Doses: 5 mg/kg and 10 mg/kg Route of Administration: intraperitoneally (ip) injected; 5 days Experimental Results: Protected mice from LPS (20 mg/kg)-induced sepsis. Survival at day 5 was 13.3% in control group where septic mice were treated by vehicle, while the values were 37.5% and 56.3% for 5 mg/kg and 10 mg/kg. In vivo animal experiments for JH-X-119-01 hydrochloride are conducted in mouse models of sepsis, such as LPS-induced sepsis. Mice are administered JH-X-119-01 hydrochloride via oral gavage or intraperitoneal injection, followed by LPS challenge. Survival rates, body temperature, and clinical scores are monitored. Inflammatory cytokine levels in serum are measured by ELISA. The compound's ability to ameliorate sepsis is determined by its effects on survival and the reduction of pro-inflammatory cytokine production. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for JH-X-119-01 hydrochloride are limited. As a small molecule with a molecular weight of 488.93 g/mol and a molecular formula of C25H21ClN6O3, JH-X-119-01 hydrochloride is expected to have moderate oral bioavailability and tissue distribution. The compound is soluble in DMSO. Further pharmacokinetic studies would be required to fully characterize its absorption, distribution, metabolism, and excretion (ADME) properties, including half-life, Cmax, AUC, and clearance.
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| Toxicity/Toxicokinetics |
Toxicology data for JH-X-119-01 hydrochloride are limited. The compound is used for research purposes only and is not approved for human use. No significant toxicities have been reported in the available literature. As an IRAK1 inhibitor, the compound may have immunomodulatory effects that could impact host defense against infections. Careful evaluation of safety and potential off-target effects would be required for therapeutic development.
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| References | |
| Additional Infomation |
JH-X-119-01 hydrochloride (CAS: 2591344-30-6) is a potent and selective IRAK1 inhibitor. It has a molecular formula of C25H21ClN6O3 and a molecular weight of 488.93. JH-X-119-01 hydrochloride ameliorates LPS-induced sepsis in mice. Combining JH-X-119 with ibrutinib shows synergism in MYD88 mutated cells. JH-X-119-01 hydrochloride is not approved for human use and is intended for research purposes only.
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| Molecular Formula |
C25H21CLN6O3
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|---|---|
| Molecular Weight |
488.9256
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| Exact Mass |
488.136
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| CAS # |
2591344-30-6
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| Related CAS # |
JH-X-119-01;2227368-54-7
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| PubChem CID |
131704491
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| Appearance |
Light yellow to yellow solid powder
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
35
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| Complexity |
738
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl[H].O=C(C1C([H])=C([H])C([H])=C(C=1[H])N([H])C(C([H])=C([H])[H])=O)N([H])C1C([H])=C([H])C(=C([H])C=1[H])N([H])C(C1=C([H])C([H])=C([H])C(C2=C([H])C([H])=NN2[H])=N1)=O
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| InChi Key |
BUFHXMGSECIZAM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H20N6O3.ClH/c1-2-23(32)27-19-6-3-5-16(15-19)24(33)28-17-9-11-18(12-10-17)29-25(34)22-8-4-7-20(30-22)21-13-14-26-31-21;/h2-15H,1H2,(H,26,31)(H,27,32)(H,28,33)(H,29,34);1H
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| Chemical Name |
N-[4-[[3-(prop-2-enoylamino)benzoyl]amino]phenyl]-6-(1H-pyrazol-5-yl)pyridine-2-carboxamide;hydrochloride
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
DMSO: 50 mg/mL (102.26 mM)
H2O: < 0.1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.11 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
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. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.11 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0453 mL | 10.2264 mL | 20.4528 mL | |
| 5 mM | 0.4091 mL | 2.0453 mL | 4.0906 mL | |
| 10 mM | 0.2045 mL | 1.0226 mL | 2.0453 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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