SB-505124-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemESB-505124Cat. No.: HY-13521CAS No.: 694433-59-5分式: CHNO分量: 335.4作靶点: TGF- Receptor作通路: TGF-beta/Smad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 : 113.33 mg/mL (337.90 mM; Need ultrasonic)

2、Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.9815 mL 14.9076 mL 29.8151 mL5 mM 0.5963 mL 2.9815 mL 5.9630 mL10 mM 0.2982 mL 1.4908 mL 2.9815 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；澄清的储备液可以根据储存条件，适当保存；以下溶剂

3、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 (7.45 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (7.45 mM); Clear solutionBIOLOGICAL ACTIVITY1/3 Master of Small Molecules 您边的抑制剂师www.MedChemE物活性 SB-505124种选择性的 TGF-

4、Receptor type I receptor (ALK4，ALK5，ALK7) 抑制剂，对 LK4，ALK5 的IC50 值分别为 129 nM 和 47 nM，对 ALK1，2，3 或 6 作。IC50 & Target IC50: 129 nM (ALK4), 47 nM (ALK5)体外研究 SB-505124 demonstrates no toxicity to renal epithelial A498 cells at concentrations up to 100 M for 48 h.505124 inhibits the closely related ALK4 wi

5、th an IC50 value of 12911 nM (about 2.5-fold less sensitive thanALK5) but does not inhibit ALK2 at concentrations up to 10 M. SB-505124 (1 M) inhibits the TGF-induced phosphorylation of Smad2 in all three of these cell lines in a concentration-dependent fashion. SB-505124 (1 or 5 M) potently inhibit

6、s TGF-induced activation of JNK/SAP, extracellular signal-regulatedkinase 1/2, and p38 despite the different patterns of activation in these cells 1. SB-505124 (10 M) impairsSmad2 phosphorylation and CTGF and -SMA expression in vitro 2. SB-505124 susspresses CTGF and -SMA observed by immunofluoresce

7、nce. Cell outgrowth from explants dissected from eyes to which SB-505124 is applied during GFS is robust while outgrowth is poor from those treated with MMC 3.PROTOCOLKinase Assay 1 Briefly, phospho-p38 is immunoprecipitated from 200 g of cell lysates with an immobilized phosphor-p38antibody overnig

8、ht at 4C. p38 kinase activity is measured using 2 g of ATF-2 fusion protein as thesubstrate with addition of 200 M ATP. After a 30-min incubation at 30C, the reaction is terminated withLaemmLi sample buffer, and the proteins are boiled and resolved by 10% SDS-polyacrylamide gelelectrophoresis, trans

9、ferred to nitrocellulose membrane, and immunoblotted with phospho-ATF-2 antibody.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 Cell viability is measured as described previously or by using the modified tetrazolium salt WST-1.Approximatel

10、y 2000 cells are seeded in 96-well dishes in 100 L of 0.2% FBS phenol red-free mediaovernight. The cells are treated with 50 L of SB-505124 (to achieve the final concentrations indicated) for 30min before being treated with or without TGF-1 and TNF- to a final volume of 200 L. Cell growth ismeasured

11、 at the indicated time points by incubating each well with 10 L of WST-1 for 3 h at 37C.Metabolically active cells cleave WST-1 to water-soluble formazan, which is directly quantitated with anenzyme-linked immunosorbent assay plate reader. Each experiment is done at least twice, and treatment foreac

12、h cell line is done in triplicate.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Bone Res. 2019 Mar 6;7:8. Oncogene. 2019 Mar;38(12):2056-2075. Development. 2018 Aug 6;145(15). pii: dev162586. J Cell Physiol. 2019 May 29. Patent. US20180263

13、995A1.See more customer validations on HYPERLINK / www.MedChemE2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEREFERENCES1. DaCosta Byfield S, et al. SB-505124 is a selective inhibitor of transforming growth factor-beta type I receptors ALK4, ALK5, and ALK7.Mol Pharmacol. 2004 Mar;65(3):744-52.2. S

14、utariya V, et al. Thermoreversible gel for delivery of receptor-like kinase 5 inhibitor SB-505124 for glaucoma filtration surgery. PharmDev Technol. 2013 Jul-Aug;18(4):957-62.3. Sapitro J, et al. Suppression of transforming growth factor- effects in rabbit subconjunctival fibroblasts by receptor-like kinase 5inhibitor. Mol Vis. 2010 Sep 16;