GNE-495 - MAP4K 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEGNE-495Cat. No.: HY-100343CAS No.: 1449277-10-4分式: CHFNO分量: 405.42作靶點(diǎn): MAP4K作通路: MAPK/ERK Pathway儲(chǔ)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(shí)驗(yàn) DMSO : 2.17 mg/mL (5.35 mM; Need ultrasonic)Mass So

2、lvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.4666 mL 12.3329 mL 24.6658 mL5 mM 0.4933 mL 2.4666 mL 4.9332 mL10 mM - - -請(qǐng)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(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。體內(nèi)實(shí)驗(yàn) 請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?，配制前?qǐng)先配制澄清的儲(chǔ)備液，再依次添加助溶劑(為保證實(shí)驗(yàn)結(jié)果的可靠性，體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲(chǔ)備液可以根據(jù)儲(chǔ)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(qǐng)依序添加

3、每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 0.22 mg/mL (0.54 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 0.22 mg/mL (0.54 mM); Clear solution3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 0.22 mg/mL (0.54 mM); Clear solution1/2 Master of Small Mole

4、cules 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 GNE-495是有效，選擇性的 MAP4K4 抑制劑，IC50 值3.7 nM。IC50 & Target MAP4K43.7 nM (IC50)體外研究 GNE-495 is a potent and selective MAP4K4 inhibitor with efficacy in retinal angiogenesis. GNE-495 showsthe best balance of MAP4K4 inhibition, permeability, microsomal stabili

5、ty, and cellular potency 1.體內(nèi)研究 GNE-495 is administered intraperitoneally to neonatal mouse pups at high doses: 25 and 50 mg/kg. GNE-495 shows good in vivo profile in all species tested, with low clearances, moderate terminal half-lives, andreasonable oral exposure levels (F=37-47%) 1.PROTOCOLAnimal

6、 Rats, Mice and Pups 1Administration 1 For the brain cassette study, three male Sprague-Dawley (SD) rats are dosed with intravenous (IV) bolus ofsix test compounds (e.g., GNE-495; 0.5 mg/kg). For the mouse PK study, female CD-1 mice areadministered IV bolus doses of GNE-495 (1 mg/kg). In addition, f

7、emale CD-1 mice are administered GNE-495 (5 mg/kg) via oral (PO) gavage. A dosing volume of 2 mL/kg is used for the rat brain cassette PK and 5mL/kg is used for all other dosing. Animals are not fasted prior to dose administration, and water and foodare available ad libitum. Following administration

8、 of the compound of interest, three blood samples (60 L)are collected at each time point from individual mice up to either 9 or 24 hours post-dose using a serialsampling approach. Immediately upon collection, the blood is mixed with K2EDTA and stored on ice or in achilled Kryorack prior to centrifug

9、ation to obtain plasma. Within 1 hr of collection, blood samples arecentrifuged at approximately 1000-2000 g for 10-15 min at 4C, and plasma is harvested. The plasmasamples are stored at -70 to -80C until analysis. For neonate PK, 3-day old CD1 pups are injected with 25mg/kg and 50 mg/kg GNE-495 int

10、raperitoneally, blood samples are collected at the time points indicated,retinas are collected one hour post-dose and snap frozen in liquid nitrogen and stored at -80C until analysis.Plasma and retinal lysate concentrations are determined by LC/MS/MS.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Ndubaku CO et al. Structure-Based Design of GNE-495, a Potent and Selective MAP4K4 Inhibitor with Efficacy in Retinal Angiogenesis.ACS Med Chem Lett. 2015 Jun 29;6(8):913-8.McePdfHeightCaution: Product has not bee