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25mg |
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JH-X-119-01 (JH-X119-01) is a novel, potent, selective and covalent inhibitor of IRAK1 (interleukin-1 receptor-associated kinases 1) (IC50 = 9 nM) with anticancer activity.
ln Vitro |
When added to LPS-treated macrophages in vitro, JH-X-119-01 (10 μM) decreases NF-κB phosphorylation as well as IL-6 and TNFα mRNA. The monomer JH-X-119-01 phosphorylates IRAK1 in an inhibitory manner [1]. Just YSK4 and MEK3—two additional disruptors—showed off-target inhibition in JH-X-119-01. The IC50 of YSK4 was found to be 57 nM by dose-response analysis[2]. In a group of Waldenstrom's macroglobulin-coupled (WM) cells, DLBCL cells, and tumor cells that expressed MYD88 differently, JH-X-119-01 displayed the majority of the cell killing effects, or EC50. The range is from 0.59 to 9.72 μM[2].
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ln Vivo |
In mice given lipopolysaccharide (LPS), JH-X-119-01 lowers immune disease and raises the even rate. At a dosage of 5 mg/kg, JH-X-119-01 raises even rates. Upon reaching a dosage of 10 mg/kg
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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: LPS (100 ng/mL)-induced decrease in IκBα and NF-κB-P65 phosphorylation. |
Animal Protocol |
Animal/Disease Models: C57BL/6 (20-22g, male) mouse [1]
Doses: 5mg/kg and 10mg/kg Route of Administration: intraperitoneal (ip) injection; the survival rate is further improved [1 ]. 5-day Experimental Results: Protection of mice from LPS (20 mg/kg)-induced sepsis. The control group of septic mice treated with vehicle had a survival rate of 13.3% on day 5, while the survival rates at 5 mg/kg and 10 mg/kg were 37.5% and 56.3%, respectively. |
References |
[1]. Bin Pan, et al. Selective inhibition of interleukin-1 receptor-associated kinase 1 ameliorates lipopolysaccharide-induced sepsis in mice. Int Immunopharmacol. 2020 Aug;85:106597.
[2]. John M Hatcher, et al. Discovery of a Selective, Covalent IRAK1 Inhibitor with Antiproliferative Activity in MYD88 Mutated B-Cell Lymphoma. ACS Med Chem Lett. 2020 Oct 9;11(11):2238-2243. |
Molecular Formula |
C25H20N6O3
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Molecular Weight |
452.474
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Exact Mass |
452.16
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Elemental Analysis |
C, 66.36; H, 4.46; N, 18.57; O, 10.61
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CAS # |
2227368-54-7
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Related CAS # |
JH-X-119-01 hydrochloride;2591344-30-6
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Appearance |
Solid powder
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SMILES |
O=C(C1C=CC=C(C=1)NC(C=C)=O)NC1C=CC(=CC=1)NC(C1=CC=CC(C2=CC=NN2)=N1)=O
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Chemical Name |
N-(4-(3-Acrylamidobenzamido)phenyl)-6-(1H-pyrazol-5-yl)picolinamide
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Synonyms |
JH-X119-01 JH-X-11901 JH-X 11901 JH-X-119-01 JH-X 119-01JH-X11901 JHX11901 JHX-11901 JHX 11901
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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 |
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 : ~125 mg/mL (~276.27 mM)
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.98 mg/mL (4.38 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 19.8 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.  (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.2101 mL | 11.0505 mL | 22.1009 mL | |
5 mM | 0.4420 mL | 2.2101 mL | 4.4202 mL | |
10 mM | 0.2210 mL | 1.1050 mL | 2.2101 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.