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.
Physicochemical Properties
| Molecular Formula | C25H20N6O3 |
| Molecular Weight | 452.46 |
| Exact Mass | 452.16 |
| Elemental Analysis | C, 66.36; H, 4.46; N, 18.57; O, 10.61 |
| CAS # | 2227368-54-7 |
| Related CAS # | JH-X-119-01 hydrochloride;2591344-30-6 |
| PubChem CID | 131704492 |
| Appearance | Light yellow to brown solid powder |
| LogP | 2.6 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 34 |
| Complexity | 738 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | WQVPGYMGERDXLH-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C25H20N6O3/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) |
| Chemical Name | N-(4-(3-Acrylamidobenzamido)phenyl)-6-(1H-pyrazol-5-yl)picolinamide |
| Synonyms | JH-X119-01 JH-X-11901 JH-X 11901 JH-X-119-01 JH-X 119-01JH-X11901 JHX11901 JHX-11901 JHX 11901 |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological 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]. |
| 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 |
| 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]. Selective inhibition of interleukin-1 receptor-associated kinase 1 ameliorates lipopolysaccharide-induced sepsis in mice. Int Immunopharmacol. 2020 Aug;85:106597. [2]. 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. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~125 mg/mL (~276.27 mM) |
| 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 | 11.0507 mL | 22.1014 mL | |
| 5 mM | 0.4420 mL | 2.2101 mL | 4.4203 mL | |
| 10 mM | 0.2210 mL | 1.1051 mL | 2.2101 mL |