Ruboxistaurin-hydrochloride-LY-333531-hydrochloride-DataSheet-生命科学试剂-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作靶点: PKC作通路: Epigenetics; TGF-beta/Smad储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month

2、溶解性数据体外实验 DMSO : 6.67 mg/mL (13.21 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液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

3、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. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 0.67 mg/mL (1.33 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 0.67 mg/mL (1.33 mM); Clear solution3. 请依序添加每种溶剂： 10% DMSO

4、90% corn oil1/3 Master of Small Molecules 您边的抑制剂师www.MedChemESolubility: 0.67 mg/mL (1.33 mM); Precipitated solutionBIOLOGICAL ACTIVITY物活性 Ruboxistaurin hydrochloride种选择性的，ATP-竞争性的 PKC 抑制剂，对 PKCI 和 PKCII 的 IC50值分别为 4.7 和 5.9 nM，对 PKC (IC50，52 nM)，PKC (IC50，360 nM)，PKC (IC50，300 nM) 和 PKC(IC50，250 nM

5、) 的抑制作相对较弱，对 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)体外研究 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.体内研究 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 您边的抑制剂师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.户使本产品发表的科研献 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