AS2677131
AS2677131 is a potent and orally active PIKfyve inhibitor. AS2677131 inhibits f IL-12p40, IL-6 and IL-1β through a PIKfyve-c-Rel pathway. AS2677131 selectively inhibits DNA-binding activity of c-Rel to IL-12p40 and IL-1β promoter. AS2677131 inhibits MHC class II expression on B cells. AS2677131 can be used for the researches of inflammation and immunology, such as arthritis.
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- CAS. Nr.: 2171502-44-4
- Formel: C27H30N6O2
- Molecular Weight:470.57
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Speicherung:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biologische Aktivität
Beschreibung
IC50 & Target
[1]|
IL-12 |
IL-1β |
IL-6 |
MHC II |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| RAW264.7 | IC50 |
2.4 nM
Compound: 69; AS2677131
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Antiinflammatory activity in mouse RAW264.7 cells assessed as effect on LPS induced IL-12p40 level measured after 24 hrs by RT-qPCR analysis
Antiinflammatory activity in mouse RAW264.7 cells assessed as effect on LPS induced IL-12p40 level measured after 24 hrs by RT-qPCR analysis
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[PMID: 37981443] |
In Vitro
AS2677131 inhibits IL-12p40 production with an IC50 of 2.4 nM and inhibits IL-1β and IL-6 levels in RAW264.7 mouse macrophage cells[1].
AS2677131 (0.1-10000 nM) inhibits IL-12p40 and IL-6 in mouse peritoneal macrophages[1].
AS2677131 (0.1-10000 nM) inhibits IL-12p40 and IL-6 in mouse bone marrow-derived dendritic cells[1].
AS2677131 (10 μM) shows no significant effect on intracellular Ca2+ influx in Ramos cells[1].
AS2677131 (200 nM) inhibits PI (3,5) P2 production by more than 90% in RAW264.7 cells[1].
AS2677131 (100 nM, 2 h) increases the size of RAW264.7 cells and induces numerous small vesicles in the cytoplasm[1].
AS2677131 (10-100 nM, 2h) decreases the promoter activity and inhibits the binding of c-Rel to the promoters of IL-12p40 and IL-1β in RAW264.7 cells[1].
AS2677131 (100 nM, 2 h) reduces p-Akt levels in RAW264.7 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:RAW264.7 cells
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Concentration:100 nM
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Incubation Time:2 h
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Result:Reduced p-Akt levels.
In Vivo
AS2677131 (1-10 mg/kg, p.o.) reduces the expression of MHC class II molecules on the surface of CD45R+ B cells in rats[1].
AS2677131 (1-10 mg/kg, p.o., daily for 24 days) reduces inflammation in rats with adjuvant-induced arthritis[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Rats with adjuvant-induced arthritis[1]
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Dosage:1, 3 and 10 mg/kg
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Administration:Orally administration, daily for 24 days
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Result:Reduced paw swelling (swelling inhibition rates of 34.3% and 78.3% at doses of 3 and 10 mg/kg, respectively).
Reversed body weight loss.
Decreased joint histological scores (including bone destruction, cartilage destruction, synovial thickening, and inflammatory cell infiltration.
Reduced the proportion of CD3-CD45RA+CD62Llow activated B cells in peripheral blood.
Chemical Information
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CAS. Nr. 2171502-44-4
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Molecular Weight 470.57
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Formel C27H30N6O2
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SMILES
O=C(C1=CC=C(NC(C)=C2CC)C2=N1)NC3=CN=CC(C4=CC=C(N5C[C@@H](C)O[C@@H](C)C5)N=C4)=C3
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Please store the product under the recommended conditions in the Certificate of Analysis.
Protokoll
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RNA extraction experimental
By lysing cells, releasing RNA, and removing impurities such as proteins and DNA, high-purity RNA products are finally obtained. The commonly used traditional method is the guanidine isothiocyanate/phenol/chloroform method (Trizol), which is suitable for a variety of animal materials including animal tissues, microorganisms, cultured cells, etc., and most plant materials.
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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.
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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
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Pyroptosis Solutions
Pyroptosis is a lytic inflammatory cell-death pathway executed by gasdermin pores, most classically through inflammasome-mediated activation of caspase-1, cleavage of gasdermin D, membrane pore formation, LDH release, and secretion of IL-1β and IL-18. The canonical pathway is commonly modeled by priming cells with an inflammatory signal such as LPS to induce pro-IL-1β and inflammasome components, followed by an activation signal such as ATP or nigericin to activate NLRP3, ASC speck formation, caspase-1 cleavage, GSDMD cleavage, cytokine release, and pyroptotic membrane rupture. The non-canonical pathway is triggered when cytosolic LPS activates mouse caspase-11 or human caspase-4/5, leading to GSDMD cleavage and pyroptosis, and this can secondarily activate NLRP3-dependent IL-1β release. Pyroptosis is linked to inflammatory injury, infection, cancer, liver disease, ocular disease, placental inflammation, and other disease phenotypes, but unresolved questions include which gasdermin fam
Reinheit & Dokumentation
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Calculators
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