GSK189254A-GSK189254-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEGSK189254ACat. No.: HY-14111CAS No.: 720690-73-3Synonyms: GSK189254分式: CHNO分量: 351.44作靶點: Histamine Receptor作通路: GPCR/G Protein; Immunology/Inflammation; NeuronalSignaling儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 month

2、s-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 25 mg/mL (71.14 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.8454 mL 14.2272 mL 28.4544 mL5 mM 0.5691 mL 2.8454 mL 5.6909 mL10 mM 0.2845 mL 1.4227 mL 2.8454 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。體內(nèi)實驗請根據(jù)您的實驗動物和給藥式選擇適當(dāng)?shù)娜芙獍?，配制前請先配制澄清的儲備?/p>

3、，再依次添加助溶劑(為保證實驗結(jié)果的可靠性，體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲備液可以根據(jù)儲存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (7.11 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (7.11 mM); Clear solution1/3 Master of

4、 Small Molecules 您邊的抑制劑師www.MedChemE3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (7.11 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 GSK189254A (GSK189254)個新穎效有選擇性的H3受體拮抗劑，對類和H3的pKi值分別為9.59-9.90 and 8.51-9.17。IC50 & Target pKi: 9.59-9.90 (H3, human), 8.51-9.17 (H3, rat) 1體外研究 GSK189254 has h

5、igh affinity for both recombinant H3 receptors expressed in HEK-293-MSR-II cells andnative H3 receptors expressed in the cerebral cortex of several species. GSK189254 generally exhibitshigher affinity for human and pig H3 receptors compared with rat,mouse, and dog H3 receptors.3HGSK189254 binds in r

6、at and human brain areas, including cortex and hippocampus. GSK189254 mayhave therapeutic potential for the symptomatic treatment of dementia in Alzheimers disease and othercognitive disorders 1.體內(nèi)研究 GSK189254 (0.3-3 mg/kg p.o.) increases the release of acetylcholine, noradrenaline, and dopamine in

7、theanterior cingulate cortex and acetylcholine in the dorsal hippocampus. GSK189254 significantly improvesperformance of rats in diverse cognition paradigms, including passive avoidance, water maze, objectrecognition, and attentional set shift 1. In Ox+/+ and Ox/ mice, acute administration of GSK189

8、254increases W and decreases slow wave and paradoxical sleep to a similar degree to modafinil, while itreduces narcoleptic episodes in Ox/ mice 2.PROTOCOLAnimal Rats: Pharmacokinetic studies with GSK189254 are conducted in conscious male Sprague-Dawley rats.Administration 12 Animals receives an intr

9、avenous infusion of GSK189254 (n=3) administered at a nominal dose level of 1 mgof free base/kg for 1 h via the femoral vein cannula (10 mL/h/kg). GSK189254 is dissolved in 0.9% (w/v)saline at a target concentration of 0.1 mg free base/mL and filtered with a 0.22-mm Millex-GV filter beforeadministra

10、tion. After a ish out of at least 2 days, the same rats received a single oral administration ofGSK189254 by gastric gavage to achieve a target dose of 2 mg of free base/kg. GSK189254 is formulated in1% (w/v) aqueous methylcellulose at a target concentration of 0.4 mg free base/mL 1.Mice: The vehicl

11、e consists of 0.05 mL NaCl at 0.9% containing methylcellulose at 1%. GSK189254 isdissolved in vehicle solution. The effects of acute and repeat administration of GSK189254 on the sleep-wake cycle in wild-type (Ox+/+) and orexin knockout (Ox/) mice is investigated. GSK189254 (3 and 10mg/kg, p.o.) is

12、administered on the sleep-wake cycle in Ox+/+ and Ox/ mice, dosed at 10 h. The oraladministration dose of GSK189254 is 10 mg/kg 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE1. Medhurst AD,

13、et al. GSK189254, a novel H3 receptor antagonist that binds to histamine H3 receptors in Alzheimers disease brain andimproves cognitive performance in preclinical models. J Pharmacol Exp Ther. 2007 Jun;321(3):1032-45.2. Guo RX, et al. Differential effects of acute and repeat dosing with the H3 antagonist GSK189254 on the sleep-wake cycle andnarcoleptic episodes in Ox-/- mice.Br J Pharmacol. 2009 May;157(1):104-17.M