CP-376395 - CRFR Antagonist - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemECP376395Cat. No.: HY-14130CAS No.: 175140-00-8分式: CHNO分量: 326.48作靶点: CRFR作通路: GPCR/G Protein储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 100 mg/mL (306.30 mM)H2O : 40% PEG300 5% Tween-80

2、 45% salineSolubility: 2.5 mg/mL (7.66 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (7.66 mM); Suspended solution; Need ultrasonic1/2 Master of Small Molecules 您边的抑制剂师www.MedChemE3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (7.66 mM); Clear so

3、lutionBIOLOGICAL ACTIVITY物活性 CP 376395有效和选择性的 CRF1 受体拮抗剂。IC50 & Target CRF1 1体外研究 CP 376395 fully antagonizes oCRF-stimulated adenylate cyclase activity in rat cerebral cortex and at humanCRF1 receptors with an apparent Ki value of 12 nM, indicating antagonist functional activity. It is highlyselect

4、ive for the human CRF1 receptor subtype; affinity for the CRF2 receptor is 10000 nM. It showsaffinities greater than 1 M against 40 neurotransmitter receptor and ion channels 1.体内研究 In the CNS, systemically administered CP 376395 blocks the effects of both exogenous and endogenousCRF. Pretreatment w

5、ith CP 376395 reverses the excitation of locus coeruleus neurons induced by icv CRF(3 g) with an ID50 of completely blocked the enhanced startle response induced by icv CRF (1 g) at 17.8mg/kg, p.o. and partially blocked at 10 mg/kg, p.o. without significantly altering baseline startle. Theattenuatio

6、n of fear-potentiated startle is statistically significant at lower doses (0.32-3.2 mg/kg, p.o., with 62-83% blockade) and completely reversed by CP 376395 at 10 mg/kg, p.o 1.PROTOCOLAnimal Dogs: Four beagle dogs (two male and two female) weighing between 8 and 15 kg are administered 1Administration

7、 1 mesylate salt or CP 376395 hydrochloride salt (1.0 mg/kg) into the cephalic vein of the foreleg. The dosingsolution for 1 is neat ethanol (15.4 mg/mL) and for CP 376395 is sterile saline at pH 2 (10 mg/mL). Oraldosing is conducted by gavage with drugs suspended in 0.1% methyl cellulose at pH 2. F

8、or the intravenousand fasted oral legs of the study, animals have last eaten approximately 21 h prior to drug administration andare permitted food and water approximately 3.5 h postdose. In the fed oral leg of the study, the animals aregiven one can of wet dog food 1 h before dosing. Blood samples a

9、re collected by venipuncture of the jugularvein prior to drug administration and at time points of 0.083 (i.v. only), 0.25, 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0,12, and 24 h postdose, processed to obtain serum and stored frozen until the day of analysis 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Chen YL, et al. 2-aryloxy-4-alkylaminopyridines: discovery of novel corticotropin-releasing factor 1 antagonists. J Med Chem. 2008 Mar13;51(5):1385-92.McePdfHeightCaution: Product has not been fully validate