PC-C7
PC-C7 is an orally active TLR4/MD2 inhibitor with Kd values of 696 nM and 764 nM for binding to TLR4 and MD2, respectively. PC-C7 inhibits the production of pro-inflammatory cytokines, the production of NO, and the expression of matrix-degrading enzymes. PC-C7 protects cells from inflammation-induced Apoptosis. PC-C7 alleviates joint swelling and protects subchondral bone structure. PC-C7 can be used for research on osteoarthritis.
For research use only. We do not sell to patients.
- Formula: C26H37NO4
- Molecular Weight:427.58
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
IC50 & Target
[1]|
TLR4 696 nM (Kd) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| RAW264.7 | IC50 |
0.17 μM
|
Inhibition of nitric oxide production in LPS-stimulated RAW264.7 macrophages incubated 24 hrs measured by nitric oxide detection kit at 560 nm.
Inhibition of nitric oxide production in LPS-stimulated RAW264.7 macrophages incubated 24 hrs measured by nitric oxide detection kit at 560 nm.
|
5433017 |
| RAW264.7 | IC50 |
68.70 nM
|
Inhibition of IL-6 release from LPS-stimulated RAW264.7 macrophages incubated 24 hrs.
Inhibition of IL-6 release from LPS-stimulated RAW264.7 macrophages incubated 24 hrs.
|
5433017 |
| RAW264.7 | IC50 |
54.54 nM
|
Inhibition of TNF-α release from LPS-stimulated RAW264.7 macrophages incubated 24 hrs.
Inhibition of TNF-α release from LPS-stimulated RAW264.7 macrophages incubated 24 hrs.
|
5433017 |
| RAW264.7 | CC50 |
256.73 μM
|
Cytotoxicity against murine RAW264.7 macrophages assessed as viability by MTT assay after 24 hrs incubation.
Cytotoxicity against murine RAW264.7 macrophages assessed as viability by MTT assay after 24 hrs incubation.
|
5433017 |
In Vitro
PC-C7 (200-400 nM; 2 h pre-exposure; 24 h LPS stimulation) disrupts TLR4-MD2 complex formation in RAW264.7 cells without altering total TLR4 or MD2 expression[1].
PC-C7 (200-400 nM; 24 h) suppresses TLR4/MD2-mediated MyD88/TRAF6/NF-κB inflammatory signaling in LPS-stimulated RAW264.7 macrophages[1].
PC-C7 (0.078-10 μM; 24 h) inhibits NO production with an IC50 of 0.17 µM and suppresses IL-6 and TNF-α release in LPS-stimulated RAW264.7 macrophages[1].
PC-C7 (0-25 μM) directly binds both TLR4 and MD2, with KD values of 696 nM and 764 nM, respectively[1].
PC-C7 (60 min) exhibits limited in vitro liver microsomal metabolism, with 75.1% parent compound remaining after 60 min[1].
PC-C7 (0-500 μM; 24 h) has low cytotoxicity in RAW264.7 cells with a CC50 of 256.73 µM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:RAW264.7 cells
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Concentration:0-500 μM
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Incubation Time:24 h (PC-C7); 4 h (MTT)
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Result:Low cytotoxicity was observed; CC50 = 256.73 μM (text).
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Sprague-Dawley (male and female, 220-250 g)[1]
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Dosage:10 mg/kg (oral gavage); 20 mg/kg (oral gavage); 1 μg/μL, 20 μL (intra-articular injection)
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Administration:oral gavage; intra-articular injection; once daily; 10 consecutive days
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Result:Reduced joint swelling and promoted recovery of joint thickness over the observation period, with overall efficacy comparable to Dex (Figure 8A,B; img-p10-b6-1).
Alleviated ACLT-induced joint tissue damage, with improved tissue architecture and reduced inflammatory lesions (Figure 8C; img-p10-b8-1).
Significantly reduced elevated IL-1β, IL-6, and TNF-α levels in synovial tissues of ACLT-induced OA rats (Figure 8D-F).
Micro-CT showed partially preserved joint bone structure and significantly restored BV/TV and BMD in diseased animals (Figure 9A-C; img-p11-b4-1).
In synovial tissues, reduced TLR4, MD2, MyD88, and TRAF6 protein levels and decreased the p-p65/p65 ratio after both systemic and intra-articular administration, with the 20 mg/kg dose producing stronger inhibition than 10 mg/kg (Figure 10A-F).
Immunofluorescence showed that increased p-NF-κB p65 and MyD88 signals in model rat synovial tissues were reduced (Figure 11; img-p12-b3-1).
Reduced MMP3 and MMP13 fluorescence signals in rat joint tissues, with more pronounced effects in the 20 mg/kg and intra-articular injection groups (Figure S3A,B).
Chemical Information
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Molecular Weight 427.58
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Formula C26H37NO4
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SMILES
CN(CCCCCCCC)CC1=C(O)C(C(C(C)=C(C)O2)=O)=C2C3=C1OC(C)(C)C=C3
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)