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SB-408124

Catalog No. S1545 Name Selleck Chemicals
CAS Number 288150-92-5 Website http://www.selleckchem.com
M. F. C19H18F2N4O Telephone (877) 796-6397
M. W. 356.3692264 Fax (832) 582-8590
Purity Email sales@selleckchem.com
Storage -20°C Chembase ID: 73135

SYNONYMS

IUPAC name
3-(6,8-difluoro-2-methylquinolin-4-yl)-1-[4-(dimethylamino)phenyl]urea
IUPAC Traditional name
3-(6,8-difluoro-2-methylquinolin-4-yl)-1-[4-(dimethylamino)phenyl]urea
Synonyms
SB408124

DATABASE IDS

CAS Number 288150-92-5

PROPERTIES

Target OX1
Salt Data Free Base
Storage Condition -20°C

DETAILS

Description (English)
Biological Activity
Description SB-408124 (Tocris-1963) is a non-peptide antagonist for OX1 with Ki of 57 nM and 27 nM in both whole cell and membrane, respectively.
Targets

OX1 (whole cell)

OX1 (membrane)

IC50

57 nM (Ki)

27 nM (Ki) [1]

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. [1] 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. [2]
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. [3] Intracerebroventricular pretreatment with SB-408124 (50 mM, 5 μL/h) prevents Bicuculline (BIC)-induced increases in endogenous glucose production (EGP). [4]
Clinical Trials
Features
Protocol
Kinase Assay [1]
Whole cell binding assays After overnight culture in 96-well Packard Cultur plates, the medium is discarded and cells are incubated in buffer containing 150 mM NaCl, 20 mM HEPES and 0.5% bovine serum albumin (pH 7.4) for 60 minutes at 25 °C. Saturation studies are carried out by incubating cells with a range of concentrations of [3H]SB-408124 (0.2–24 nM); the total assay volume is 250 μL. Protein content is assayed by lysing cells with 0.1M NaOH and using the Bradford method with bovine serum albumin (BSA) as a standard. Association kinetic studies are performed by measuring the specific binding of [3H]SB-408124 (3 nM) at 1–60 minutes after addition of [3H]SB-408124. All assays are terminated by washing the cells three times with 250μL ice-cold phosphate-buffered saline. A volume of 100 μL of Microscint 40 is added to each well and the plate is left at room temperature for 2 hours. Cell-associated radioactivity is then measured using a Packard Topcount, with a count time of 2 minute/well.
Membrane-based SPA binding assays CHO-K1_OX1 cell membranes (75 μg/mL) are precoupled by shaking with wheatgerm-agglutinin polyvinyltoluene (WGA-PVT) scintillation proximity assay (SPA) beads (5 mg/mL) in buffer containing 25 mM HEPES, 2.5 mM MgCl2, 0.5 mM EDTA and 0.025% bacitracin (pH 7.4) at 4 °C for 1 hour. The bead-membrane suspension is centrifuged at 300× g and resuspended in the same volume of room temperature assay buffer. A volume of 100 μL of bead-membrane suspension is incubated with [3H]SB-674042 (5 nM) in a total assay volume of 200 μL in a 96-well Packard Optiplate to give a final protein concentration of 7.5 μg/well. Nonspecific binding is measured as that remaining in the presence of 3 μM SB-408124. Assay plates are shaken for 10 min and then incubated at room temperature for 4 hours before being counted on a Packard TopCount scintillation counter (count time 2 min/well). Saturation studies are carried out by incubating bead-membranes (equivalent to 7.5 μg protein/well and 2.5 mg beads/mL) with a range of concentrations of [3H]SB-674042 (0.1–20 nM). Protein content is assayed using the Bradford method using bovine serum albumin as a standard. Association kinetic studies are performed by measuring specific binding of [3H]SB-674042 (5 nM) at 1–30 min after addition of bead-membranes (equivalent to 7.5 μg protein/well and 2.5 mg beads/mL). For dissociation studies, bead-membranes are first incubated with [3H]SB-674042 (5 nM) for 30 min. Specific binding is then measured at 2–120 min after the addition of 3 μM SB-408124. Competition studies are performed by incubating bead-membranes (equivalent to 7.5 μg protein/well and 2.5 mg beads/mL) with [3H]SB-674042 (5 nM) and a range of concentrations of the test compound.
Animal Study [3]
Animal Models Male Wistar rats
Formulation SB-408124 is dissolved in saline.
Doses 30 μg/10 μL
Administration Intracerebroventricularly (i.c.v.) injected into the lateral ventricle of the rat.
References
[1] Langmead CJ, et al, Br J Pharmacol, 2004, 141(2) , 340-346.
[2] Woldan-Tambor A, et al, Pharmacol Rep, 2011, 63(3), 717-723.
[3] Kis Gk, et al, Pflugers Arch, 2012, 463(4), 531-536
[4] Yi CX, et al, Diabetes, 2009, 58(9), 1998-2005.