SH494
SH494 is a p38 MAPK inhibitor and Nrf2 pathway activator. SH494 inhibits RANKL-induced phosphorylation of p38 and disrupts the MAPK cascade associated with osteoclastogenesis. SH494 activates the Nrf2 pathway, upregulates downstream target genes and induces the expression of cytoprotective enzymes. SH494 reduces intracellular ROS accumulation and restores mitochondrial membrane potential (ΔΨm) to normal. SH494 decreases osteoclast activity and alleviates osteoporosis symptoms in ovariectomized mice. SH494 can be used for research on osteoporosis.
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- Fòrmula: C31H34N4O2
- Peso molecular:494.63
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
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Chemical Information
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Actividad biológica
SH494 (0.01-1 μM; 7 days) potently inhibits RANKL-induced osteoclast differentiation in mouse bone marrow macrophages (BMMs), with an IC50 of 8.4 nM, and achieves complete inhibition at concentrations ≥0.1 μM following 7 days of treatment[1].
SH494 (0.01-1 μM; 7 days) dose-dependently inhibits RANKL-induced F-actin ring formation in mouse bone marrow macrophages (BMMs)[1].
SH494 (0.01-1 μM; 1-5 days) dose-dependently and time-dependently downregulates the mRNA expression of key osteoclastogenic genes in mouse bone marrow macrophages (BMMs) treated with RANKL and M-CSF[1].
SH494 (0.01-1 μM; 72 h) dose-dependently inhibits the protein expression of key osteoclastogenic markers (c-Fos, Ctsk, Mmp9) in mouse bone marrow-derived macrophages (BMMs)[1].
SH494 (1 μM; 5-30 min) inhibits RANKL-induced phosphorylation of p38 MAPK in mouse bone marrow macrophages (BMMs) at 5, 10, and 30 min following RANKL stimulation[1].
SH494 (0.01-1 μM; 48-72 h) reduces RANKL-induced ROS accumulation in mouse bone marrow macrophages (BMMs) and restores their mitochondrial membrane potential after 48 h; meanwhile, it activates the Nrf2 pathway by upregulating the expression of Cat, Gclc and HO-1, as well as increasing the nuclear localization of Nrf2[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:mouse bone marrow-derived macrophages (BMMs)
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Concentration:0.01 μM (48 h), 0.1 μM (48 h), 1 μM (48 h; 1, 3, 5 days)
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Incubation Time:48 h (concentration-dependent analysis); 1, 3, 5 days (time course with 1 μM SH494)
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Result:Dose-dependently downregulated the mRNA expression of key osteoclastogenic markers: Nfatc1, Trap, Ctsk, Mmp9, and c-Fos after 48 h.
Over a 5-day time course, 1 μM SH494 abrogated RANKL-induced upregulation of Nfatc1, Trap, Ctsk, and c-Fos throughout differentiation.
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Cell Line:mouse bone marrow-derived macrophages (BMMs)
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Concentration:0.01 μM, 0.1 μM, 1 μM
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Incubation Time:72 h
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Result:Dose-dependently reduced the protein levels of c-Fos, Ctsk, and Mmp9 in RANKL-stimulated BMMs.
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Cell Line:mouse bone marrow-derived macrophages (BMMs)
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Concentration:1 μM
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Incubation Time:pretreated, then incubated with RANKL for 5, 10, 30 min
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Result:Markedly inhibited RANKL-induced phosphorylation of p38 at all tested time points.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (8-week-old female; osteoporosis induced by bilateral ovariectomy)[1]
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Dosage:1 mg/kg; 5 mg/kg
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Administration:i.p.; once daily; 6 weeks
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Result:Increased bone volume fraction (BV/TV) by 40.66%, trabecular number (Tb.N) by 28.35%, and bone surface density (BS/TV) by 33.43% relative to vehicle-treated OVX mice at 5 mg/kg.
Dose-dependently prevented OVX-induced bone microstructural deterioration, with the 5 mg/kg dose showing improvement in Tb.N and BS/TV comparable to positive control teriparatide.
Preserved trabecular architecture and reduced osteoclast numbers in treated groups.
Showed no systemic or organ-specific toxicity, with stable body weights and normal histology of major organs.
Chemical Information
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Peso molecular 494.63
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Fòrmula C31H34N4O2
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SMILES
C[C@]12[C@]([H])([C@@]3(CCC4=CC(CC[C@@]4(C3=CC2)C)=O)[H])CC(C1=NC5=NC=NN65)=C6C7=CC=C(C=C7)OCCC
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
SH494 Related Classifications
HY-182818 Related Classifications
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