GNE-495 - MAP4K 抑制剂 - 生命科学试剂 - 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作靶点: MAP4K作通路: MAPK/ERK Pathway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 : 2.17 mg/mL (5.35 mM; Need ultrasonic)Mass So

2、lvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.4666 mL 12.3329 mL 24.6658 mL5 mM 0.4933 mL 2.4666 mL 4.9332 mL10 mM - - -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，并请注意储备液的保存式和期限。体内实验 请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加

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

4、cules 您边的抑制剂师www.MedChemEBIOLOGICAL ACTIVITY物活性 GNE-495是有效，选择性的 MAP4K4 抑制剂，IC50 值3.7 nM。IC50 & Target MAP4K43.7 nM (IC50)体外研究 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.体内研究 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