JH-X-119-01

• CAS: 2227368-54-7
• Catalog Number: ACM2227368547
• Category: Inhibitors
• Molecular Weight: 452.47
• Molecular Formula: C25H20N6O3
• Description: Jh-X-119-01 is a novel potent and selective interleukin-1 receptor-associated kinases 1 (IRAK1) inhibitor. JH-X-119-01 irreversibly labels IRAK1 at C302. This compound exhibited cytotoxic activity at single digit micromolar concentrations in a panel of WM, DLBCL, and lymphoma cell lines expressing MYD88. Cotreatment of JH-X-119-01 with the BTK inhibitor ibrutinib resulted in synergistic killing effects in these systems.
• Synonyms: JH-X-119-01; JH-X119-01; JH-X 119-01; JH-X-11901; JH-X11901; JH-X 11901; JHX-11901; JHX11901; JHX 11901
• IUPAC Name: N-(4-(3-Acrylamidobenzamido)phenyl)-6-(1H-pyrazol-5-yl)picolinamide
• Canonical SMILES: O=C(NC1=CC=C(NC(C2=CC=CC(NC(C=C)=O)=C2)=O)C=C1)C3=NC(C4=CC=NN4)=CC=C3
• InChI: 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)
• InChI Key: WQVPGYMGERDXLH-UHFFFAOYSA-N
• Solubility: Soluble in DMSO
• Appearance: Solid powder
• Shelf Life: >3 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Alternative CAS: 2227368-54-7 (free base); 2591344-30-6 (HCl)
• Biological Target: IRAK1
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 66.36; H, 4.46; N, 18.57; O, 10.61
• Exact Mass: 452.1597
• HS Tariff Code: 2934.99.9001
• In Vitro Activity: The discovery of a highly potent and selective covalent inhibitor of IRAK1, JH-X-119-01 was reported. Intact protein MS labeling studies confirmed that JH-X-119-01 irreversibly labels IRAK1 at C302. This compound exhibited cytotoxic activity at single digit micromolar concentrations in a panel of WM, DLBCL, and lymphoma cell lines expressing MYD88. Cotreatment of JH-X-119-01 with the BTK inhibitor ibrutinib resulted in synergistic killing effects in these systems. Taken together, JH-X-119-01 represents a highly selective probe of IRAK1 for further development.; Reference: Hatcher JM, Yang G, Wang L, Ficarro SB, Buhrlage S, Wu H, Marto JA, Treon SP, Gray NS. 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. doi: 10.1021/acsmedchemlett.0c00378. PMID: 33214835; PMCID: PMC7667833.
• In Vivo Activity: Jh-X-119-01 selectively inhibited IRAK1 phosphorylation comparing with a non-selective IRAK1/4 inhibitor which simultaneously inhibited phosphorylation of IRAK1 and IRAK4. Both Jh-X-119-01 and IRAK1/4 inhibitor increased survival of septic mice, but Jh-X-119-01-treated mice had higher blood CD11b+ cell counts than IRAK1/4 inhibitor-treated ones [24 h: (1.18 ± 0.26) × 106/ml vs. (0.79 ± 0.20) × 106/ml, p = 0.001; 48 h: (1.00 ± 0.30) × 106/ml vs. (0.67 ± 0.23) × 106/ml, p = 0.042]. IRAK1/4 inhibitor induced more apoptosis of macrophages than Jh-X-119-01 did in vitro. IRAK1/4 inhibitor decreased protein levels of anti-apoptotic BCL-2 and MCL-1 in RAW 264.7 and THP-1 cells, an effect not seen in Jh-X-119-01-treated cells. In conclusion, Jh-X-119-01 selectively inhibited activation of IRAK1 and protected mice from LPS-induced sepsis. Jh-X-119-01 showed less toxicity on macrophages comparing with a non-selective IRAK1/4 inhibitor.; Reference: Pan B, Gao J, Chen W, Liu C, Shang L, Xu M, Fu C, Zhu S, Niu M, Xu K. Selective inhibition of interleukin-1 receptor-associated kinase 1 ameliorates lipopolysaccharide-induced sepsis in mice. Int Immunopharmacol. 2020 Aug;85:106597. doi: 10.1016/j.intimp.2020.106597. Epub 2020 May 13. PMID: 32422509.
• Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).