Free shipping on all orders over $ 500

SB-649868

Cat. No. M8966
SB-649868 Structure
Synonym:

GSK649868

Size Price Availability
5mg USD 430 1-2 Weeks
10mg USD 690 1-2 Weeks
Free Delivery on orders over USD 500 Bulk Inquiry?

Quality Control
  • Current batch:
  • Purity >98%
  • COA
  • MSDS
Biological Activity

SB-649868 is a selective orally active orexin (OX) receptor antagonist with pKi values of 9.4 and 9.5 at the OX1 and OX2 receptor, respectively. SB-649868 antagonizes orexin-A-induced inositol 1 phosphate (IP1) accumulation with the following pKB value (OX1=9.67; OX2=9.64). SB-649868 displaces the [3H]ACT-078573 receptor binding with the following pKi values: OX1=9.27; OX2=8.91. SB-649868, administered orally 3 h before OX-A injection at doses of 1, 3 and 10 mg/kg, causes a dose-dependent reduction of OX-A induced grooming as measured by total time spent grooming and number of grooming bouts (p <0.01 at 3 and 10 mg/kg po).

Protocol
Cell Experiment
Cell lines Chinese Hamster Ovary (CHO) cells
Preparation method Chinese Hamster Ovary (CHO) cells stably transfected with human OX1 orexin receptor are cultured in Dulbecco's modified Eagle's medium F12 Ham, supplemented with 10% fetal bovine serum (FBS), 2 mg/mL glutamine, 600 μg/ml geneticin at 37 °C in an atmosphere of 95% air and 5% CO2. CHO cells stably transfected with human OX2 orexin receptor are cultured in alpha-MEM supplemented with 10% FBS, 100 units/mL penicillin G, 100 units/mL streptomycin and 400 μg/mL geneticin, at 37 °C in an atmosphere of 95% air and 5% CO2. Accumulation of IP1 is measured using IP-One HTRF terbium cryptate-based assay. OX1-CHO cells are seeded into white 384-well plate at the cell density of 1×104 cells per well and cultured for 24 h in the presence of 5 mM sodium butyrate while OX2-CHO cells are seeded at the cell density of 4×104 cells per well and cultured for 24 h in culture medium. After washings Hank's Balanced Salt Solution (HBSS) at room temperature containing 20 mM HEPES pH 7.4, 50 mM, LiCl and 0.1% Bovine Serum Albumin (BSA) cells are pre-incubated for 45 min with antagonist and then treated with agonist for 60 min at 37 °C. Detection reagents, IP1-d2 tracer and anti-IP1-cryptate are diluted in lysis buffer and added to the cells. Following 60 min incubation at room temperature, time-resolved fluorescence at 615 nm and 665 nm are measured with Envision Multilabel flash lamp reader with 100 flashes and 400 μs integration time.
Concentrations final DMSO concentration not exceeding 0.5% for functional studies and 1% for binding studies
Incubation time 45 min
Animal Experiment
Animal models
Formulation
Dosages
Administration
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 477.55
Formula C26H24FN3O3S
CAS Number 380899-24-1
Purity >98%
Solubility DMSO 10 mM
Storage at -20°C
References

Functional and binding kinetic studies make a distinction between OX1 and OX2 orexin receptor antagonists.
Faedo S, et al. Eur J Pharmacol. 2012 Oct 5;692(1-3):1-9. PMID: 22796453.

Discovery process and pharmacological characterization of a novel dual orexin 1 and orexin 2 receptor antagonist useful for treatment of sleep disorders.
Di Fabio R, et al. Bioorg Med Chem Lett. 2011 Sep 15;21(18):5562-7. PMID: 21831639.

Phase I studies on the safety, tolerability, pharmacokinetics and pharmacodynamics of SB-649868, a novel dual orexin receptor antagonist.
Bettica P, et al. J Psychopharmacol. 2012 Aug;26(8):1058-70. PMID: 21730017.

Related OX Receptor Products
MK-1064

MK-1064 is a potent, selective and orally active Orexin OX2 Receptor Antagonist for the research of insomnia.

SB-334867

SB-334867 is a selective non-peptide orexin OX1 receptor antagonist with a pKb value of 7.2.

TCS-1102

TCS 1102 is a potent, dual orexin receptor antagonist (Ki values are 0.2 and 3 nM for OX2 and OX1 receptors respectively).

MK-3697

MK-3697 is an isonicotinamide small molecule, acting as a potent and selective Orexin 2 receptor antagonist with Ki = 0.95 nM.

SB408124

SB408124 (Tocris-1963) is a non-peptide antagonist for OX1 receptor with Ki of 57 nM and27 nM in both whole cell and membrane, respectively, exhibits 50-fold selectivity over OX2 receptor.

  Catalog
Abmole Inhibitor Catalog 2017




Keywords: SB-649868, GSK649868 supplier, OX Receptor, inhibitors

Contact Us

Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2017 AbMole BioScience. All Rights Reserved.