| Chemical Properties | Back Directory | [density ]
1.28±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : 50 mg/mL (119.18 mM; ultrasonic and warming and adjust pH to 2 with HCl and heat to 80°C) | [form ]
Solid | [pka]
12.32±0.43(Predicted) | [color ]
Off-white to light yellow | [InChIKey]
NPEMHKSMWPZEOV-UHFFFAOYSA-N | [SMILES]
O=C(C1=CC=CC(C(NC2=NC3=C(N2CCC)C=C(CN4CCCCC4)C=C3)=O)=C1)N |
| Hazard Information | Back Directory | [Uses]
HS-276 is an orally active, potent and highly selective TAK1 inhibitor, with a Ki of 2.5 nM. HS-276 shows significant inhibition of TAK1, CLK2, GCK, ULK2, MAP4K5, IRAK1, NUAK, CSNK1G2, CAMKKβ-1, and MLK1, with IC50 values of 8.25, 29, 33, 63, 125, 264, 270, 810, 1280, and 5585 nM, respectively. HS-276 can be used for rheumatoid arthritis (RA) research[1]. | [Biological Activity]
HS-276 is an orally activepotent and selective TGF-β-activated kinase-1 (TAK-1; TAK1) inhibitor (Ki = 2.5 nM; IC50 = 8.25 nM) th at significantly reduced cytokines production in THP-1 human macrophages upon LPS/IFNγ treatment (IC50 = 138 nM/TNF201 nM/IL-6and 234 nM/IL-1β). HS-276 effectively attenuates arthritic-like symptoms in the CIA mouse rheumatoid arthritis (RA) model (10-30 mg/kg/d p.o. or 25 mg/kg/d i.p.). | [in vivo]
HS-276 (CIA mouse model of inflammatory arthritis, 50 mg/kg, IP, daily for 6 days) reduces inflammation, pannus, cartilage damage (CD), bone resorption (BR), and periosteal bone formation (PBF) histological manifestations[1].
HS-276 (CD-1 mice, 30 mg/kg, Oral gavage, once) shows excellent bioavailability in mice with a Cmax of 3.68 μM and %F of 98.1%[1]. | [IC 50]
IRAK1: 264 nM (IC50); IRAK4: 2500 nM (IC50) | [References]
[1] Scarneo S, et al. Development and Efficacy of an Orally Bioavailable Selective TAK1 Inhibitor for the Treatment of Inflammatory Arthritis. ACS Chem Biol. 2022 Mar 18;17(3):536-544. DOI:10.1021/acschembio.1c00788 |
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| Company Name: |
Merck KGaA
|
| Tel: |
21-20338288 |
| Website: |
www.sigmaaldrich.cn |
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