JH-X-119-01
new
featured

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 535214

CAS#: 2227368-54-7 (free base)

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.


Chemical Structure

img
JH-X-119-01
CAS# 2227368-54-7 (free base)

Theoretical Analysis

MedKoo Cat#: 535214
Name: JH-X-119-01
CAS#: 2227368-54-7 (free base)
Chemical Formula: C25H20N6O3
Exact Mass: 452.1597
Molecular Weight: 452.474
Elemental Analysis: C, 66.36; H, 4.46; N, 18.57; O, 10.61

Price and Availability

Size Price Availability Quantity
50.0mg USD 750.0 2 Weeks
100.0mg USD 1250.0 2 Weeks
200.0mg USD 1850.0 2 Weeks
500.0mg USD 2850.0 2 Weeks
1.0g USD 3850.0 2 Weeks
2.0g USD 6450.0 2 Weeks
Bulk inquiry

Related CAS #: 2227368-54-7 (free base)   2591344-30-6 (HCl)    

Synonym: 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/Chemical Name: N-(4-(3-Acrylamidobenzamido)phenyl)-6-(1H-pyrazol-5-yl)picolinamide

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)

SMILES Code: O=C(NC1=CC=C(NC(C2=CC=CC(NC(C=C)=O)=C2)=O)C=C1)C3=NC(C4=CC=NN4)=CC=C3

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: 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.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >3 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Product Data:

Biological target: IRAK1
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.

Preparing Stock Solutions

The following data is based on the product molecular weight 452.474 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 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 vitro protocol: 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 protocol: 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.

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.
=
x
x
g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

=
÷

Dilution Calculator

Calculate the dilution required to prepare a stock solution.
x
=
x

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.