2. Metabolic Enzyme/Protease NF-κB Immunology/Inflammation
  3. Heme Oxygenase (HO) Reactive Oxygen Species (ROS) NO Synthase COX Interleukin Related
  4. SIN 14

SIN 14, a derivative of Sinomenine (HY-15122), is an orally active HO-1 activator (KD = 17.2 μM). SIN 14 binds to the catalytic core domain of HO-1 and induces HO-1 activation in catalysis. SIN 14 significantly increases HO-1 stability. SIN 14 has anti-inflammatory effects and inhibits M1 macrophage polarization while promoting M2 polarization in LPS (Lipopolysaccharides)(HY-D1056)-induced RAW264.7 cells. SIN 14 inhibits inflammatory mediator production (eg: NO, IL-6, IL-1β and CCL2, inhibits production of ROS and down-regulates the expression of COX-2 and iNOS. SIN 14 can inhibit RA-related inflammatory edema in collagen-induced arthritis (ClA) mice.

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SIN 14

SIN 14 Chemical Structure

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SIN 14 Related Antibodies

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HO-1 HO-2

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nNOS iNOS eNOS

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COX COX-1 COX-2 COX-3

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IL-1 IL-2 IL-3 IL-4 IL-5 IL-6 IL-8 IL-10 IL-12 IL-13 IL-15 IL-17 IL-23 IL-7 IL-33 IL-22

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Description

SIN 14, a derivative of Sinomenine (HY-15122), is an orally active HO-1 activator (KD = 17.2 μM). SIN 14 binds to the catalytic core domain of HO-1 and induces HO-1 activation in catalysis. SIN 14 significantly increases HO-1 stability. SIN 14 has anti-inflammatory effects and inhibits M1 macrophage polarization while promoting M2 polarization in LPS (Lipopolysaccharides)(HY-D1056)-induced RAW264.7 cells. SIN 14 inhibits inflammatory mediator production (eg: NO, IL-6, IL-1β and CCL2, inhibits production of ROS and down-regulates the expression of COX-2 and iNOS. SIN 14 can inhibit RA-related inflammatory edema in collagen-induced arthritis (ClA) mice[1].

IC50 & Target[1]

HO-1

17.2 μM (Kd)

iNOS

 

COX-2

 

IL-6

 

IL-1β

 

In Vitro

SIN 14 (2.5-10 μM, 24 h) can inhibit NO release in LPS-induced RAW 264.7 (IC50 = 4.97 μM), BMDM (IC50 = 3.88 μM), and BV-2 cells (IC50 = 3.88 μM)[1].
SIN 14 (2.5-10 μM, 24 h) significantly suppresses the release of inflammatory factors, including NO, IL-6, IL-1β, and CCL2, and down-regulates the expression of COX-2 and iNOS upon LPS-induced RAW 264.7 cells[1].
SIN 14 (50 μM) inhibits inflammatory cells migration and aggregation induced by CuSO4 in Tg (zlyz: EGFP) transgenic zebrafish line[1].
SIN 14 (10 μM, 24 h) inhibits M1 macrophage polarization while promoting M2 polarization in LPS-induced RAW264.7 cells[1].
SIN 14 (10 μM, 4 h or 20 min) significantly increases HO-1 stability (4 h) and enhances HO-1 resistance to pronase-induced proteolysis (20 min)[1].
SIN 14 (2.5-10 μM, 24 h) can inhibit NO production and TNF-α release, and these effects were reduced in HO-1 siRNA-transfected cells[1].
SIN 14 (10 μM, 24 h) inhibits ROS levels in LPS-induced RAW 264.7 cells by activating HO-1 (detected with the DCFH-DA probe (HY-D0940))[1].

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

SIN 14 Related Antibodies

Real Time qPCR[1]

Cell Line: LPS induced-RAW 264.7 cells
Concentration: 10 μM
Incubation Time: 24 h
Result: Significantly inhibited CXCL10 release and enhanced the expression of IL-10, inhibited M1 macrophage polarization.

Immunofluorescence[1]

Cell Line: LPS induced-RAW 264.7 cells
Concentration: 10 μM
Incubation Time: 24 h
Result: Enhanced the expression of CD206, Arg-1, promoted M2 polarization
In Vivo

SIN 14 (10 mg/kg, 50 mg/kg, p.o., once daily, 36 days) reduces joint swelling in both the fore and hind limbs, effectively suppresses the progression of cartilage injury and promotes the repair of bone erosion in the CIA DBA/1 mice[1].

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

Animal Model: Male DBA/1 mice, 7-8 weeks old, weighing 18-20 g, were injected with bovine type II collagen and Complete Freund's Adjuvant (CFA)(HY-153808). 21 days later, they were boosted with bovine type II collagen and Incomplete Freund's Adjuvant (IFA)(HY-153808A) for 16 days of induction[1].
Dosage: 10 mg/kg, 50 mg/kg
Administration: p.o., once daily for 36 days
Result: Alleviated joint swelling in both the forelimbs and hindlimbs.
Showed significant improvements in BV/TV, BMD and Tb.Th, showed notable reduction in Tb.Sp.
Decreased cartilage and bone damage as well as reduced pannus formation.
Effectively curbed the abnormal proliferation of synovial cells and alleviated damage to both cartilage and bone.
The mean paw area was markedly restored compared to the model mice.
Significantly decreased the number of TRAP-positive cells in the ankle joints compared to the CIA group, indicating the inhibitory effect on RA-related osteoclast differentiation.
Decreased 8-OHdG expression in the joint tissues.
Molecular Weight

375.85

Formula

C20H22ClNO4
SMILES

COC1=CC=C2C[C@H](N3C)C4[C@@]5(CC3)C(C(O)OC1=C52)=C(Cl)C(OC)=C4
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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SIN 14 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

SIN 14SIN14SIN-14Heme Oxygenase (HO)Reactive Oxygen Species (ROS)NO SynthaseCOXInterleukin RelatedHeme OxygenaseNitric oxide synthasesNOSCyclooxygenaseILRheumatoid ArthritisHeme Oxygenase-1HO-1Collagen-induced arthritisCIAROSCOX-2iNOS Macrophage polarizationInflammationAllosteric regulationInhibitorinhibitorinhibit

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