1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEA-1165442Cat. No.: HY-12428CAS No.: 1221443-94-2分式: CHClFNO分量: 431.86作靶點: TRP Channel作通路: Membrane Transporter/Ion Channel; Neuronal Signaling儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO :

2、 100 mg/mL (231.56 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.3156 mL 11.5778 mL 23.1557 mL5 mM 0.4631 mL 2.3156 mL 4.6311 mL10 mM 0.2316 mL 1.1578 mL 2.3156 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)娜芙獍福渲魄罢埾扰渲瞥吻宓膬湟?，再?/p>

3、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 (5.79 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.79 mM); Clear solution1/2 Master of Small Molecules

4、您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 A-1165442有效，競爭性，有服活性的 TRPV1 拮抗劑，對TRPV1的 IC50 值為 9 nM。IC50 & Target IC50: 9 nM (human TRPV1) 1體外研究 A-1165442 displays potent, competitive antagonism at recombinant human TRPV1 activated by capsaicin(IC50=9 nM) and incomplete blockade of acid-evoked response (

5、62% block at 30 M). A-1165442 possessesexcellent selectivity (100-fold) versus other members of the TRP family (TRPA1, TRPM8, TRPV2, TRPV3)and other receptors expressed in peripheral sensory neurons including P2X2/3, Cav2.2, Nav channels, andKCNQ2/3. A-1165442 shows minimal cross-reactivity upon eva

6、luation (10 M) in a broad screening panel(n=74, CEREP) of cell-surface receptors, ion channels, and enzymes 1.體內(nèi)研究 A-1165442 exhibits excellent pharmacological selectivity, has a favorable pharmacokinetic profile, anddemonstrates good efficacy against osteoarthritis pain in rodents. Oral administrat

7、ion of A-1165442 preventscapsaicin-induced nocifensive behaviors in rats, with an ED50 of 9.5 mol/kg corresponding to plasmaconcentration of 420 ng/mL (970 nM). A single dose of A-1165442 produces a robust effect on grip force,with an ED50 of 35 mol/kg measured 1 h postdosing. Repeated dosing of A-1

8、165442 results in an increasein potency relative to acute analgesic efficacy. No significant changes in core body temperature is observedin conscious rats dosed with A-1165442 and this temperature-neutral profile is maintained in conscious dogs1.PROTOCOLAnimal Dogs: Male beagle dogs are instrumented

9、 with telemetry transmitters capable of monitoring core bodyAdministration 1 temperature and then allowed to recover. Dosing is initiated at time zero, with dogs receiving a single oraldose of vehicle, compound 1 at (30 mol/kg), or A-1165442 (100 mol/kg); n=46 per group. Measurementsare recorded eve

10、ry 5 min for the duration of the study, then averaged to 15 min and 1 h intervals.Temperature signals are transmitted as radio signals by each implanted transmitter to a receiver placed onthe cage and interfaced with a desktop personal computer 1.MCE has not independently confirmed the accuracy of t

11、hese methods. They are for reference only.REFERENCES1. Voight EA, et al. Discovery of (R)-1-(7-chloro-2,2-bis(fluoromethyl)chroman-4-yl)-3-(3-methylisoquinolin-5-yl)urea (A-1165442): atemperature-neutral transient receptor potential vanilloid-1 (TRPV1) antagonist with analgesic efficacy. J Med Chem. 2014 Sep11;57(17):7412-24.McePdfHeightCaution: Product has not