WJH-C19
Based on 1 Customer Validation
WJH-C19 is an orally active RIPK1 inhibitor with an IC50 of 5.7 nM. WJH-C19 inhibits the RIPK1/RIPK3/MLKL signaling axis, blocks RIPK1 phosphorylation, suppresses the phosphorylation of downstream RIPK3 and MLKL, disrupts necrosome formation, and exhibits protective effects against necroptosis (Apoptosis) in multiple cell lines. WJH-C19 ameliorates symptoms of inflammatory bowel disease in a mouse colitis model by regulating the necroptosis pathway. WJH-C19 alleviates inflammation and bone destruction in a mouse model of rheumatoid arthritis. WJH-C19 is applicable to research related to inflammatory bowel disease and rheumatoid arthritis.
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- Purity: 98.65%
- 화학식: C27H22ClN5O2S
- 분자량:516.01
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보관:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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용액&용해도
- 순도&문서
- References
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Help & FAQs
Biological Activity
제품 설명
IC50 & Target
[1]|
RIPK1 5.7 nM (IC50) |
RIPK3 |
In Vitro
WJH-C19 (Compound 10e12) (25 h) exerts potent, concentration-dependent protective effects against necroptosis in multiple cell lines, with EC50 values of 0.28 nM in L929 cells, 4.0 nM in HT22 cells, 1.6 nM in HT29 cells, and 2.0 nM in U937 cells; in addition, this compound reduces necroptotic L929 cells in a dose-dependent manner[1].
WJH-C19 potently inhibits the kinase activity of RIPK1, with an IC50 value of 5.7 nM[1].
WJH-C19 (0.5-50 nM) concentration-dependently inhibits the TNFα/z-VAD-FMK (HY-16658BG) (TZ)-induced phosphorylation of RIPK1, RIPK3 and MLKL in L929 cells, as well as the mTNFα/Smac mimetic/z-VAD-FMK (TSZ)-induced phosphorylation in HT29 cells, thereby blocking necrosome formation and the downstream necroptotic signaling pathway[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Parmacokinetics
In Vivo
WJH-C19 (10-20 mg/kg; p.o.; daily; 14 days) potently ameliorates complete Freund's adjuvant (CFA, HY-153808)-induced rheumatoid arthritis in female C57BL/6 mice, reduces paw swelling, joint inflammation and bone destruction, and inhibits the RIPK1/RIPK3/MLKL signaling axis[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (female, 10-12 weeks old, ~28 g, DSS-induced colitis)[1]
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Dosage:2.5 mg/kg; 1.25 mg/kg
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Administration:p.o.; daily; 7 days
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Result:Achieved 47.5% body weight recovery, 42.9% disease activity index (DAI) reduction, and 60.5% colon length recovery at 2.5 mg/kg.
Achieved 33.2% body weight recovery, 32.1% DAI reduction, and 35.1% colon length recovery at 1.25 mg/kg.
Reduced proinflammatory cytokine levels (IL-1β, IL-6, TNFα) and increased anti-inflammatory cytokine IL-10 levels in colon tissue at both doses.
Inhibited phosphorylation of RIPK1, RIPK3, and MLKL in colonic proteins at both doses, with the high dose showing the most robust inhibition.
Reduced mucosal damage, maintained intact glandular architecture, and restored zonula occludens-1 (ZO-1) and Occludin expression at both doses, with the high-dose group exhibiting near-normal morphology.
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Animal Model:C57BL/6 (female, 8 weeks old, CFA-induced rheumatoid arthritis)[1]
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Dosage:20 mg/kg; 10 mg/kg
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Administration:p.o.; daily; 14 days
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Result:Reduced paw swelling percentage, ankle joint temperature, and arthritis index scores in a dose-dependent manner at both doses, with efficacy comparable or superior to celecoxib.
Reduced osteophyte formation and reversed bone destructive changes, including improvements in bone mineral density (BMD), cortical BMD, trabecular number (Tb.N), connectivity density (Conn.D), bone volume (BV), cortical volume (CV), trabecular separation (Tb.Sp), pore number (Po.N), cortical area (Ct.Ar), and cortical thickness (Ct.Th) at both doses, with the high dose showing the most pronounced improvement.
Reduced inflammatory cell infiltration, synovial hyperplasia, and cartilage erosion at both doses, with the high-dose group achieving histological scores approaching normal levels.
Reduced the M1/M2 macrophage ratio in spleens in a dose-dependent manner at both doses, shifting toward the anti-inflammatory M2 phenotype.
Suppressed expression of phosphorylated RIPK1, RIPK3, and MLKL in ankle joints at both doses, with the high dose showing the strongest inhibition.
Chemical Information
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Appearance Solid
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분자량 516.01
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화학식 C27H22ClN5O2S
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Color White to off-white
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SMILES
O=C(C1=CN=C2C=CC(C3=CC=C4N=C(NC(C5CC5)=O)SC4=C3)=CN21)N[C@H](C6=CC=C(Cl)C=C6)C
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
용액&용해도
In Vitro:
DMSO : 50 mg/mL (96.90 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
순도&문서
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Data Sheet (277 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
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| DMSO | 1 mM | 1.9379 mL | 9.6897 mL | 19.3795 mL | 48.4487 mL |
| 5 mM | 0.3876 mL | 1.9379 mL | 3.8759 mL | 9.6897 mL | |
| 10 mM | 0.1938 mL | 0.9690 mL | 1.9379 mL | 4.8449 mL | |
| 15 mM | 0.1292 mL | 0.6460 mL | 1.2920 mL | 3.2299 mL | |
| 20 mM | 0.0969 mL | 0.4845 mL | 0.9690 mL | 2.4224 mL | |
| 25 mM | 0.0775 mL | 0.3876 mL | 0.7752 mL | 1.9379 mL | |
| 30 mM | 0.0646 mL | 0.3230 mL | 0.6460 mL | 1.6150 mL | |
| 40 mM | 0.0484 mL | 0.2422 mL | 0.4845 mL | 1.2112 mL | |
| 50 mM | 0.0388 mL | 0.1938 mL | 0.3876 mL | 0.9690 mL | |
| 60 mM | 0.0323 mL | 0.1615 mL | 0.3230 mL | 0.8075 mL | |
| 80 mM | 0.0242 mL | 0.1211 mL | 0.2422 mL | 0.6056 mL |
WJH-C19 Related Classifications
HY-181596 Related Classifications
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