RGH-706
RGH-706 is an orally active, blood-brain barrier-permeable, selective MCH1 receptor antagonist with an IC50 of 6.2 nM against hMCHR1. RGH-706 shows no antagonistic activity against hMCH2 receptors. RGH-706 improves obesity. RGH-706 can be used in research related to obesity and Prader-Willi syndrome.
For research use only. We do not sell to patients.
- CAS No.: 2027497-52-3
- Formula: C26H27ClN4O2
- Molecular Weight:462.97
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
In Vitro
RGH-706 (60 min) is a potent MCHR1 antagonist in human MCH1-expressing cells, with an IC50 of 6.2 nM[1].
RGH-706 (3 μM; 5.5 h) has high plasma protein binding (fu = 0.0235) and high brain tissue binding (fu = 0.009) in mouse samples at 3 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (male, obese, ~45g average body weight, diet-induced obesity model)[1]
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Dosage:0.3 mg/kg; 1 mg/kg; 3 mg/kg
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Administration:p.o.; twice daily; 14 days (for 0.3,1,3 mg/kg); twice daily; 28 days (for 3 mg/kg)
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Result:Induced dose-dependent body weight loss after 14 days of treatment, with control-subtracted body weight loss of 13.1% at 3 mg/kg b.i.d.
Caused a sustained 10-30% decrease in daily food intake.
Determined an ED50 (dose for 5% weight loss) of 0.25 mg/kg p.o.
Sustained body weight loss with no habituation to treatment in a 28-day DIO study with 3 mg/kg b.i.d.
dosing.
Showed supraproportional increases in plasma and brain concentrations across the 0.3-3 mg/kg dose range: at 0.3 mg/kg, Cmax plasma was 0.175 μM and Cmax brain was 0.258 μM; at 1 mg/kg, Cmax plasma was 0.664 μM and Cmax brain was 1.010 μM; at 3 mg/kg, Cmax plasma was 2.51 μM and Cmax brain was 3.010 μM.
Achieved receptor occupancy of 24% at 0.3 mg/kg b.i.d.
and 99% at 3 mg/kg b.i.d., with corresponding Cu brain/IC50 potency ratios of 0.37 and 5.78, respectively.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 2027497-52-3
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Molecular Weight 462.97
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Formula C26H27ClN4O2
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SMILES
O=C1C=C(OCC2=NC=C(Cl)C=C2)C=CN1C3=CC4=C(N(CCN(C(C)C)CC5)C5=C4)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.
Protocols
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Research Protocol for Metabolic Diseases
AMP-activated protein kinase, AMPK, is a conserved cellular energy sensor that responds to reduced cellular energy status and coordinates metabolism by increasing ATP-generating catabolic pathways while suppressing ATP-consuming anabolic processes. In metabolic disease research, the AMPK pathway is experimentally relevant because it regulates hepatic lipid synthesis, fatty acid oxidation, glucose production, skeletal-muscle glucose disposal, mTORC1-linked biosynthesis, autophagy, mitochondrial homeostasis, and whole-body energy balance. The central pathway logic is that energy stress, metformin, exercise-like stimulation, or direct AMPK activators increase AMPKα Thr172 phosphorylation and downstream substrate phosphorylation, including ACC and RAPTOR. Phosphorylation of ACC suppresses lipogenesis and supports fatty acid oxidation, whereas phosphorylation of RAPTOR suppresses mTORC1 signaling and links cellular energy status to growth and protein synthesis control. The pathway is linked
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
RGH-706 Related Classifications
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