1、MK-3207 HydrochlorideCat. No.: HY-10302CAS No.: 957116-20-0分式: CHClFNO分量: 594.05作靶点: CGRP Receptor作通路: GPCR/G Protein; Neuronal Signaling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 (168.34 mM)* “ means soluble, but saturation unknown.Concentration
2、Solvent Mass 1 mg 5 mg 10 mg1 mM 1.6834 mL 8.4168 mL 16.8336 mL5 mM 0.3367 mL 1.6834 mL 3.3667 mL制备储备液10 mM 0.1683 mL 0.8417 mL 1.6834 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液体内实验 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.21 mM); Clear solution1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% s
3、alineSolubility: 2.5 mg/mL (4.21 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 (4.21 mM); Clear solution3. BIOLOGICAL ACTIVITY物活性 MK-3207 Hydrochloride 是种有效的，可服的 CGRP receptor 拮抗剂， IC50 值为 0.12 nM， Ki 值为 0.024 nM。IC n=14) as for human, but it 体外研究Product D
4、ata Sheet InhibitorsAgonistsScreening Librarieswww.MedChemE1displays 400-fold lower affinity for the canine and rat receptors, with values of 10 nM and 101.2 nM, respectively. MK-3207 is highly selective versus the human AM1 (CLR/RAMP2) and AM2 (CLR/RAMP3) receptors, with Ki values of 16,500 nM and
5、15617 nM, respectively. MK-3207 maintains a high degree of selectivity versus human CTR, with a Ki value of 1.90.58 M. MK-3207 also displays good selectivity versus the AMY3 (CTR/RAMP3) receptor, with a Ki value of 12825 nM, but it is less selective versus the AMY1 (CTR/RAMP1) receptor, with a Ki va
6、lue of 0.750.13 nM. MK-3207 potently blocks human -CGRP-stimulated cAMP responses in human CGRP receptor-expressing HEK293 cells, with an IC50 value of 0.120.02 nM. MK-3207 displays significantly lower potency for the rat CGRP receptor, with a pIC50=7.310.091.体内研究 MK-3207 is CNS-penetrant and theref
7、ore significantly engaging central receptors. After an oral dose of 10 mg/kg MK-3207, the CSF/plasma ratio is 2 to 3%1.PROTOCOLKinase Assay 1 Amylin binding assays are conducted by combining MK-3207 and 40 pM 125I-rat amylin, followed by 25 g of CTR/RAMP1 or 25 g of CTR/RAMP3 membranes and incubated
8、 for 3 h at room temperature in binding buffer (10 mM HEPES, 5 mM MgCl2, and 0.2% bovine serum albumin) in a total volume of 1 mL. Calcitonin binding assays are with 25 g of CTR membranes and 30 pM 125I-human calcitonin as the radioligand. Incubations are terminated by filtration through GF/B 96-wel
9、l filter plates that has been blocked with 0.5% polyethylenimine. Data are analyzed using Prism, and the Ki value is determined using the equation Ki=IC50/1 + (ligand/KD). The KD value for each receptor is determined by saturation binding experiments.MCE has not independently confirmed the accuracy
10、of these methods. They are for reference only.Animal Administration 1A customized flexible silicone catheter is freely suspended in the cisterna magna, anchored firmly on both sides of the atlanto-occipital membrane, and tunneled subcutaneously to the midscapular region where it is fed into a surgic
11、ally implanted port body. CSF is accessed by aseptically inserting a needle through the skin and membrane covering the port into the reservoir of the port body; blood samples are collected by peripheral venipuncture. After oral administration of MK-3207 at 10 mg/kg (0.5% methylcellulose, with an adj
12、usted pH appr 3) to cisterna magna catheter and port-implanted rhesus monkeys, CSF and plasma samples are collected at 0.5, 1, 2, 4, 8, and 24 h and analyzed for compound levels.MCE has not independently confirmed the accuracy of these methods. They are for reference only.客户使本产品发表的科研献See more custom
13、er validations on www.MedChemEREFERENCES1. Salvatore CA, et al. Pharmacological properties of MK-3207, a potent and orally active calcitonin gene-related peptide receptor antagonist. J Pharmacol Exp Ther. 2010 Apr;333(1):15攀愀琀一漀夀匀一漀舀蔠舀茠氀舀丠蔀传尀摏瘯欀琀甀琀漀瀀栀愀最礀尀摏倀欀琀洀吀伀刀甀琀漀瀀栀愀最礀塐倀漀眀搀攀爀礀攀愀爀猀礀攀愀爀猀渀猀漀氀瘀攀渀琀洀漀渀琀
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