R-7050-TNF-α-Antagonist-III-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemER-7050Cat. No.: HY-110203CAS No.: 303997-35-5Synonyms: TNF- Antagonist III分式: CHClFNS分量: 380.77作靶点: TNF Receptor作通路: Apoptosis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 : 25 mg/mL (65.66

2、 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.6263 mL 13.1313 mL 26.2626 mL5 mM 0.5253 mL 2.6263 mL 5.2525 mL10 mM 0.2626 mL 1.3131 mL 2.6263 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，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

3、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. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.57 mM); Suspended solution; Need ultrasonic2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (6.57 mM); Clear solution3. 请依序添加每种溶剂： 10% DMSO 90% corn oil1/

4、2 Master of Small Molecules 您边的抑制剂师www.MedChemESolubility: 2.5 mg/mL (6.57 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 R-7050种肿瘤坏死因受体 (TNFR) 拮抗剂，对 TNF 具有更选择性。IC50 & Target TNF体外研究 R-7050 is a potent and fully reversible hit with greater selectivity toward TNF. In TNF-induced intercellularadhesion mole

5、cule 1 (ICAM-1) expression, R-7050 inhibition potency (EC50=0.63 M) is 2- to 3-fold greaterthan EC50 for IL-1-induced ICAM-1 expression (EC50=1.45 2 M). R-7050 inhibits phosphorylation of boththe JNK pathway (MKK4, JNKs, and ATF2) and p38 pathway (MKK3/6, p38, and MAPKAP2) 1. R-7050 is acell-permeab

6、le triazoloquinoxaline compound that selectively inhibits TNF- induced cellular signaling. Unlikebiologic TNF inhibitors (e.g. Infliximab, Etanercept, Adalimumab) that directly bind TNF- and function asdecoy receptors, R-7050 does not affect binding of TNF- to TNFR. In contrast, R-7050 selectively i

7、nhibitsthe association of TNFR with intracellular adaptor molecules (e.g. TRADD, RIP), limits receptorinternalization, and prevents subsequent cellular responses after TNF- binding 2.体内研究 R-7050 (6 mg/kg) reduces Evans blue extravasation to 28.75.9 g and 30.31.9 g Evans blue/g braintissue when admin

8、istered at 0.5 h or 2 h post-ICH, respectively (p 2.PROTOCOLAnimal Mice 2Administration 2 A mouse collagenase model of ICH is utilized. Briefly, male CD-1 mice (8-10 weeks old) are placed into astereotactic frame and a 0.5 mm diameter burr hole is drilled over the parietal cortex, 2.2 mm lateral to

9、thebregma. A 26-gauge Hamilton syringe, loaded with 0.04 U of bacterial type IV collagenase in 0.5 L saline, islowered 3 mm deep from the skull surface directly into the left striatum. The syringe is depressed at a rate of450 nL/min and left in place for several minutes after the procedure to preven

10、t solution reflux and excessdiffusion. Sham animals undergo the same surgical procedure, except that saline is stereotactically injectedrather than collagenase. After the syringe is removed, bone wax is used to close the burr hole, the incision issurgically stapled, and mice are kept warm until reco

11、very of the righting reflex. R-7050 (6-18 mg/kg) isadministered via intraperitoneal route at the time of injury or up to 2 h post-ICH 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Gururaja TL, et al. A class of small molecules that inhi

12、bit TNFalpha-induced survival and death pathways viaprevention of interactionsbetween TNFalphaRI, TRADD, and RIP1. Chem Biol. 2007 Oct;14(10):1105-18.2. King MD, et al. TNF-alpha receptor antagonist, R-7050, improves neurological outcomes following intracerebralhemorrhage in mice.Neurosci Lett. 2013 May 10;542:92-6.McePdfHeight2/2 Master of Small Molecules 您边的抑制剂师www.MedChemECaution