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MedKoo Cat#: 535214 | Name: JH-X-119-01
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Description:

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

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

JH-X-119-01
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: 452.47

Elemental Analysis: C, 66.36; H, 4.46; N, 18.57; O, 10.61

Price and Availability

Size Price Availability Quantity
25mg USD 250.00 2 Weeks
50mg USD 450.00 2 Weeks
100mg USD 750.00 2 Weeks
200mg USD 1,250.00 2 Weeks
500mg USD 2,650.00 2 Weeks
1g USD 3,850.00 2 Weeks
2g USD 6,250.00 2 Weeks
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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
More Info
Product Data
Product Data
Instruction
View handling instruction
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 452.47 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.
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.