TNF-α-IN-29
TNF-α-IN-29 is an orally active and selective TNF-α inhibitor, with IC50 values of 123.0 nM against human targets, and a human Kd of 45.9 nM. TNF-α-IN-29 blocks TNF-α-TNFR1 protein-protein interactions and inhibits TNF-α-mediated inflammatory signaling pathways. TNF-α-IN-29 exhibits anti-inflammatory effects in a mouse model of collagen-induced arthritis and promotes articular cartilage repair. TNF-α-IN-29 can be used for the research of rheumatoid arthritis.
For research use only. We do not sell to patients.
- Formula: C29H27ClF3N7O
- Molecular Weight:582.02
-
Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
-
Biological Activity
-
Chemical Information
- Protocols
- Purity & Documentation
- References
-
Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
TNF-α 123 nM (IC50) |
TNF-α 45.9 nM (Kd) |
In Vitro
TNF-α-IN-29 (XS-18) binds strongly to human TNF-α protein with an FP-IC50 of 123.0 nM and a Kd of 45.9 nM, and inhibits the protein-protein interaction between TNF-α and TNFR1 with an IC50 of 36.4 nM.
TNF-α-IN-29 (up to 60 min) has enhanced in vitro metabolic stability in human liver microsomes with a half-life of 63.6 min[1].
TNF-α-IN-29 (1.37-1000 nM; 1.5 h preincubated with TNF-α, 24 h incubated with cells) neutralizes TNF-α-induced apoptosis in L929 cells[1].
TNF-α-IN-29 (20 min preincubated with TNF-α, 18 h incubated with cells) inhibits TNF-α-induced NF-κB activation in NF-κB-TA-Luc HEK293 cells with an IC50 of 126.9 nM and exhibits minimal cytotoxicity at 20 μM[1].
TNF-α-IN-29 (5-10 μM; 72 h incubated with cells, 15 min stimulated with TNF-α) blocks TNF-α-mediated NF-κB pathway activation in MH7A cells by reducing IκBα phosphorylation and suppresses IL-6 mRNA expression[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
-
Cell Line:L929 cells
-
Concentration:1.37, 12, 111, 1000 nM
-
Incubation Time:1.5 h (preincubated with TNF-α); 24 h (incubated with cells)
-
Result:Inhibited L929 cell apoptosis with a neutralization rate of 68.1% at 1 μM.
Maintained a nearly 50% inhibitory effect at a concentration of 1.37 nM.
Parmacokinetics
In Vivo
TNF-α-IN-29 (5-50 mg/kg; p.o.; twice daily; 14 days) exhibits dose-dependent anti-rheumatoid arthritis activity in the CIA mouse model, with the 50 mg/kg dose demonstrating superior efficacy to Tofacitinib (HY-40354) in reducing joint inflammation, repairing cartilage damage, and inhibiting pro-inflammatory cytokine expression (IL-6 and TNF-α)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:DBA/1J (male, 6 weeks old, 16-19 g, collagen-induced arthritis model)[1]
-
Dosage:5 mg/kg; 15 mg/kg; 50 mg/kg
-
Administration:p.o.; twice daily; 14 days
-
Result:Showed dose-dependent inhibition of hind paw volume increase and paw thickening; 15 mg/kg presented efficacy similar to tofacitinib, and 50 mg/kg showed better effects on arthritis scores.
Ameliorated joint histopathological injury dose-dependently; 50 mg/kg markedly reduced inflammatory infiltration and synovial hyperplasia, with stronger effects than tofacitinib.
Improved cartilage repair in a dose-dependent manner; 50 mg/kg significantly restored cartilage structure and exhibited superior efficacy to tofacitinib.
Dose-dependently suppressed IL-6 and TNF-α expression in ankle joints; 15 mg/kg was comparable to tofacitinib, and 50 mg/kg showed stronger inhibition.
Chemical Information
-
Molecular Weight 582.02
-
Formula C29H27ClF3N7O
-
SMILES
ClC1=C(C2=CC(C3=CN=C(N=C3)N4CCC5(CC4)CN(C5)C(N)=O)=CC=C2N=C1)NC6=CC(C)=CC=C6C(F)(F)F
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
-
Collagen-Induced Arthritis
Collagen-induced arthritis (CIA) is an autoimmune murine model of rheumatoid arthritis in which immunization with type II collagen (CII) emulsified in an adjuvant induces a T cell- and autoantibody-driven inflammatory arthritis characterized by synovial hyperplasia, immune cell infiltration, and joint destruction. The model typically relies on genetically susceptible mouse strains (e. g. , DBA/1) and reproduces key features of human rheumatoid arthritis, including anti-collagen immune responses and progressive joint inflammation. Disease onset generally occurs within ~3-4 weeks after immunization, depending on antigen/adjuvant combinations and protocol variation. The immunopathology is driven by adaptive immune activation against CII, leading to systemic and local joint inflammation mediated by pro-inflammatory cytokines and effector immune cells, making CIA a standard preclinical platform for evaluating immunomodulatory and anti-arthritic interventions.
-
Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
-
Research Protocol for Inflammation-related Diseases
The NLRP3 inflammasome is a cytosolic innate immune signaling platform that integrates priming signals and danger-signal activation to promote caspase-1 activation, maturation of IL-1β and IL-18, and gasdermin D-mediated pyroptotic cell death. The core experimental logic is to determine whether inflammatory disease phenotypes are driven by increased NLRP3 expression, ASC-containing inflammasome assembly, caspase-1 cleavage, GSDMD cleavage, and extracellular release of IL-1β/IL-18 rather than by nonspecific cell injury alone. The pathway is strongly linked to inflammation-related disease phenotypes because monosodium urate crystals activate NALP3/NLRP3 inflammasome signaling in gout-like crystal inflammation, cholesterol crystals activate NLRP3 inflammasomes in atherogenesis models, and DSS-induced intestinal inflammation has been reported to involve NLRP3 inflammasome activity. However, experimental colitis studies also show context-dependent protective effects of NLRP3 inflammasome co
-
How to Choose the Right Model Animal
Choosing the right model animal is a validity-driven decision in which the species, strain, sex, age, genetic background, disease-induction method, outcome measures, and welfare burden must match the scientific question rather than laboratory tradition or convenience. A model should be selected by judging face validity, construct validity, and predictive validity: whether it resembles the human phenotype, whether it reproduces relevant mechanisms, and whether results are likely to predict human biology or treatment response. Animal studies often fail to translate because of species differences, weak disease resemblance, poor experimental design, inadequate reporting, publication bias, and underuse of randomization, blinding, and sample-size justification. Unresolved questions include how to rank competing models objectively, how much human-disease complexity must be reproduced for a given objective, and when non-animal systems such as organoids, ex vivo tissue, or computational models
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
TNF-α-IN-29 Related Classifications
HY-182884 Related Classifications
Powered by Bioz