Ruboxistaurin-hydrochloride-LY-333531-hydrochloride-DataSheet-生命科學試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemERuboxistaurin hydrochlorideCat. No.: HY-10195BCAS No.: 169939-93-9Synonyms: LY 333531 hydrochloride分式: CHClNO分量: 505.01作靶點: PKC作通路: Epigenetics; TGF-beta/Smad儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month

2、溶解性數據體外實驗 DMSO : 6.67 mg/mL (13.21 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 1.9802 mL 9.9008 mL 19.8016 mL5 mM 0.3960 mL 1.9802 mL 3.9603 mL10 mM 0.1980 mL 0.9901 mL 1.9802 mL請根據產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。體內實驗請根據您的實驗動物和給藥式選擇適當的溶解案，配制前請先配制澄清的儲備液，再依次添加助溶劑(為保

3、證實驗結果的可靠性，體內實驗的作液，建議您現現配，當天使；澄清的儲備液可以根據儲存條件，適當保存；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: 0.67 mg/mL (1.33 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 0.67 mg/mL (1.33 mM); Clear solution3. 請依序添加每種溶劑： 10% DMSO

4、90% corn oil1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemESolubility: 0.67 mg/mL (1.33 mM); Precipitated solutionBIOLOGICAL ACTIVITY物活性 Ruboxistaurin hydrochloride種選擇性的，ATP-競爭性的 PKC 抑制劑，對 PKCI 和 PKCII 的 IC50值分別為 4.7 和 5.9 nM，對 PKC (IC50，52 nM)，PKC (IC50，360 nM)，PKC (IC50，300 nM) 和 PKC(IC50，250 nM

5、) 的抑制作相對較弱，對 PKC (IC50，100 M) 作。IC50 & Target PKCI PKCII PKC PKC4.7 nM (IC50) 5.9 nM (IC50) 52 nM (IC50) 250 nM (IC50)PKC PKC PKC300 nM (IC50) 360 nM (IC50) 600 nM (IC50)體外研究 Ruboxistaurin hydrochloride is a selective and ATP-competitive PKC inhibitor, with IC50s of 4.7 and 5.9 nMfor PKCI and PKCII,

6、 shows less potent inhibition on PKC (IC50, 52 nM), PKC (IC50, 360 nM), PKC (IC50, 300 nM), PKC (IC50, 250 nM), and has no effect on PKC (IC50, 100 M) 1. Ruboxistaurin (10 and400 nM) dramatically inhibits glucose-induced monocyte adherence to levels that are not different frombaseline adherence of m

7、onocytes to endothelial cells under NG conditions. Ruboxistaurin (10 and 400 nM)dose not alter the endothelial expression of adhesion molecules or modify endothelial cell growth 2.Ruboxistaurin (LY333531; 10 nM) reduces high-glucose (HG)-induced human renal glomerular endothelialcells (HRGECs) viabi

8、lity, and inhibits the increases in swiprosin-1 in HRGECs incubated with HG 3.體內研究 Ruboxistaurin (LY333531; 1 mg/kg/d for 8 weeks) markedly reduces GEC apoptosis as well as swiprosin-1upregulation, and ameliorates renal glomerular injury in the diabetic mice. Ruboxistaurin also potentlyattenuates th

9、e expression of PARP, cleaved-caspase9, cleaved-caspase3, and the Bax/Bcl-2 ratio, indiabetic mice 3. Ruboxistaurin (LY333531; 0.1, 1.0, or 10.0 mg/kg/d, po.o.) dramatically reduces thenumber of leukocytes trapped in the retinal microcirculation of diabetic rats 4.PROTOCOLCell Assay 2 The second pas

10、sages of human umbilical vein endothelial cells (HUVEC) are grown to confluence inmicrotiter plates coated with gelatin. The medium contains 5.5 mM glucose. If endothelial cells are stimulatedwith 27.7 mM glucose for 4 days, they are seeded in the well at a calibrated higher cell concentration in or

11、derto achieve comparable cell density at the day adhesion assays are performed. Therefore, cell density in thewells is tested thoroughly in control wells of each glucose concentration prior to monocyte adhesion assays.If Ruboxistaurin is used in this assay, it is added to the cultures for the whole

12、period 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Rats 4Administration 4 Leukocyte entrapment is evaluated only once after a 4-week diabetic period in both groups of rats with andwithout Ruboxistaurin treatment, using one eye (right eye) o

13、f each rat. Ruboxistaurin is administered orally at2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEdosages of 0.1 (n = 8), 1.0 (n = 16), and 10.0 mg/kg/d (n = 8) for 4 weeks, from the time streptozotocin isinjected in the rats. Immediately before acridine orange digital fluorography, rats are anest

14、hetized with amixture (1:1) of xylazine hydrochloride (4 mg/kg) and ketamine hydrochloride (10 mg/kg). The pupils aredilated with 0.5% tropicamide and 2.5% phenylephrine hydrochloride. A contact lens is placed on the corneato maintain transparency throughout the experiments. Each rat has a catheter

15、inserted into the tail vein and isplaced on a movable platform. Body temperature is maintained between 37C and 39C throughout theexperiment 4.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產品發(fā)表的科研獻 Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093.

16、 Endocrinology. 2018 May 1;159(5):2253-2263. Biosci Rep. 2018 Sep 7;38(5).See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Jirousek MR, et al. (S)-13-(dimethylamino)methyl-10,11,14,15-tetrahydro-4,9:16, 21-dimetheno-1H, 13H-dibenzoe,kpyrrolo3,4-h1,4,13oxadiazacyclohexadecene-1,3

17、(2H)-d ione (LY333531) and related analogues: isozyme selective inhibitors of protein kinase Cbeta. J Med Chem. 1996 Jul 5;39(14):2664-71.2. Kunt T, et al. The beta-specific protein kinase C inhibitor ruboxistaurin (LY333531) suppresses glucose-induced adhesion of humanmonocytes to endothelial cells

18、 in vitro. J Diabetes Sci Technol. 2007 Nov;1(6):929-35.3. Wang ZB, et al. LY333531, a PKC inhibitor, attenuates glomerular endothelial cell apoptosis in the early stage of mouse diabeticnephropathy via down-regulating swiprosin-1. Acta Pharmacol Sin. 2017 Jul;38(7):1009-1023.4. Nonaka A, et al. PKC-beta inhibitor (LY333531) attenuates leukocyte entrapment in retinal microci