SB-408124

SB-408124 is a elective non-peptide orexin OX1 receptor antagonist (Kb values are 21.7 and 1405 nM for human OX1 and OX2 receptors respectively). A critical role for the orexin-1 receptor (OX1R) in complex emotional behavior is emerging, such as overactivation of the OX1R pathway being associated with panic or anxiety states.

Product information

CAS Number: 288150-92-5

Molecular Weight: 356.37

Formula: C19H18F2N4O

Synonym:

SB408124 free base

SB 408124

Related CAS Number:

1431697-90-3 (SB-408124 hydrochloride)

Chemical Name: N-(6, 8-Difluoro-2-methyl-4-quinolinyl)-N'-[4-(dimethylamino)phenyl]urea

Smiles: CC1=CC(NC(=O)NC2C=CC(=CC=2)N(C)C)=C2C=C(F)C=C(F)C2=N1

InChiKey: JTARFZSNUAGHRB-UHFFFAOYSA-N

InChi: InChI=1S/C19H18F2N4O/c1-11-8-17(15-9-12(20)10-16(21)18(15)22-11)24-19(26)23-13-4-6-14(7-5-13)25(2)3/h4-10H,1-3H3,(H2,22,23,24,26)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO: 36 mg/mL(101.01 mM). Water: Insoluble.

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

SB-408124 binds hypocretin type 1 receptor (HcrtR1) with pKi values of 7.57. Calcium mobilization studies shows that SB-408124 is a functional antagonist of the OX1 receptor with a affinity of approximately 50-fold selectivity over the OX2 receptor. A recent study indicates that pretreatment of primary cultures of rat astrocytes with SB-401824 before Orexin A administration significantly reduced the stimulatory action of Orexin A on both basal and forskolin-acivated cAMP production.

In Vivo:

SB-408124 (30 μg/10 μL, administered intracerebroventricularly) decreases Orexin-A induced water intake in Wistar rats. Intracerebroventricularly administered Orexin-A (30 μg/10 μL) blocks the vasopressin (VP) level increase induced by either histamine or 2.5% NaCl administration, and this blocking effect is moderated by pretreatment with SB-408124. Intracerebroventricular pretreatment with SB-408124 (50 mM, 5 μL/h) prevents Bicuculline (BIC)-induced increases in endogenous glucose production (EGP).

References:

1. Kis Gk, et al, Pflugers Arch, 2012, 463(4), 531-536
2. Woldan-Tambor A, et al, Pharmacol Rep, 2011, 63(3), 717-723.
3. Langmead CJ, et al, Br J Pharmacol, 2004, 141(2) , 340-346.

Products are for research use only. Not for human use.