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Cat. No.: HY-182818

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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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화학식: C₃₁H₃₄N₄O₂
분자량:494.63

보관:

Please store the product under the recommended conditions in the Certificate of Analysis.

SH494 Chemical Structure

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Use of MCE Products

Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- 제품 설명
- In Vitro
- Parmacokinetics
- In Vivo
Chemical Information
순도&문서
References
Calculators
Help & FAQs
Classifications
Bioz

Biological Activity

제품 설명

All p38 MAPK Isoforms :

In Vitro

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.

Real Time qPCR^[1]

Cell Line:

mouse bone marrow-derived macrophages (BMMs)
Concentration:

0.01 μM (48 h), 0.1 μM (48 h), 1 μM (48 h; 1, 3, 5 days)
Incubation Time:

48 h (concentration-dependent analysis); 1, 3, 5 days (time course with 1 μM SH494)
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.

Western Blot Analysis^[1]

Cell Line:

mouse bone marrow-derived macrophages (BMMs)
Concentration:

0.01 μM, 0.1 μM, 1 μM
Incubation Time:

72 h
Result:

Dose-dependently reduced the protein levels of c-Fos, Ctsk, and Mmp9 in RANKL-stimulated BMMs.

Western Blot Analysis^[1]

Cell Line:

mouse bone marrow-derived macrophages (BMMs)
Concentration:

1 μM
Incubation Time:

pretreated, then incubated with RANKL for 5, 10, 30 min
Result:

Markedly inhibited RANKL-induced phosphorylation of p38 at all tested time points.

Parmacokinetics

Species	Dose	Route	T_max	C_max	AUC_0-t	AUC_0-∞	V_z	CL	T_1/2	F
Mice^[1]	1.0 mg/kg	i.v.	0.083 h	1093 ng/mL	396 ng·h/mL	399 ng·h/mL	674 mL/kg	42 mL/min/kg	0.32 h	/
Mice^[1]	10.0 mg/kg	p.o.	0.333 h	1162 ng/mL	1061 ng·h/mL	1067 ng·h/mL	/	/	0.66 h	26.8 %

In Vivo

SH494 (1-5 mg/kg; i.p.; once daily; 6 weeks) dose-dependently prevents ovariectomy-induced bone loss in mice^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

C57BL/6 (8-week-old female; osteoporosis induced by bilateral ovariectomy)^[1]
Dosage:

1 mg/kg; 5 mg/kg
Administration:

i.p.; once daily; 6 weeks
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

분자량 494.63
화학식 C₃₁H₃₄N₄O₂
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
선적

Room temperature in continental US; may vary elsewhere.
보관

Please store the product under the recommended conditions in the Certificate of Analysis.

순도&문서

Handling Instructions (2659 KB)

References

[1]. Zhang JZ, et al. Design and Synthesis of 9α-Hydroxyandrost-4-ene-3,17-dione Derivatives as Novel Potent Antiosteoporosis Agents. J Med Chem. 2026 Apr 9;69(7):8451-8475.
[Content Brief]

Calculators

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Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

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Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

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MOQ

Minimum order quantity

100 mg

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Amount: USD 0.00

Biological Activity
- 제품 설명
- In Vitro
- In Vivo
Chemical Information
순도&문서
References

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SH494

All p38 MAPK Isoforms

Biological Activity

Chemical Information

순도&문서

References

Calculators

Help & FAQs

SH494 Related Classifications

HY-182818 Related Classifications