魯伯斯塔鹽酸鹽作用機(jī)制 - Medchemexpress - MCE中國(guó)

1、Product Data SheetRuboxistaurin hydrochlorideCat. No.: HY-10195BCAS No.: 169939-93-9分式: CHClNO分量: 505.01作靶點(diǎn): PKC作通路: Epigenetics; TGF-beta/Smad儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 6.67 mg/mL (13.21 mM; Need ultrasonic)SolventMass1 mg 5 mg 10 mgConcen

2、tration制備儲(chǔ)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(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)內(nèi)使，-20C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?1 個(gè)內(nèi)使。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?。以下溶解案都?qǐng)先按照 In Vitro 式配制澄清的儲(chǔ)

3、備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的式助溶1. 請(qǐng)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 solution此案可獲得 0.67 mg/mL (1.33 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 6.7000003 mg/m

4、L 的澄清DMSO 儲(chǔ)備液加到 400 L PEG300 中，混合均勻；向上述體系中加 50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請(qǐng)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 solution此案可獲得 0.67 mg/mL (1.33 mM，飽和度未知) 的澄清溶液。Page 1 of 2 www.MedChemE以 1 mL 作液為例，取 100 L 6.7000003 mg/mL 的澄，混合均勻。DMSO 儲(chǔ)備液加到

5、900 L 20% 的 SBE-CD 理鹽溶液中3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 0.67 mg/mL (1.33 mM); Precipitated solution此案可獲得 0.67 mg/mL (1.33 mM，飽和度未知)以 1 mL 作液為例，取 100 L 6.7000003 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Ruboxistaurin hydrochloride (LY 333531 hydrochloride) 種選擇性的，ATP-競(jìng)爭(zhēng)性

6、的 PKC 抑制劑，對(duì) PKCI 和 PKCII 的 IC50 值分別為 4.7 nM 和 5.9 nM，對(duì) PKC (IC50，52 nM)，PKC (IC50，360 nM)，PKC (IC50，300 nM) 和 PKC (IC50，250 nM) 的抑制作相對(duì)較弱，對(duì) PKC (IC50，100 M) 作。IC & 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 R

7、uboxistaurin hydrochloride is a selective and ATP-competitive PKC inhibitor, with IC50s of 4.7 and 5.9 nM for PKCIand PKCII, 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 and 40

8、0 nM) dramatically inhibits glucose-induced monocyte adherence to levels that are not different from baseline adherence of monocytes to endothelialcells under NG conditions. Ruboxistaurin (10 and 400 nM) dose not alter the endothelial expression of adhesionmolecules or modify endothelial cell growth

9、2. Ruboxistaurin (LY333531; 10 nM) reduces high-glucose (HG)-inducedhuman renal glomerular endothelial cells (HRGECs) viability, and inhibits the increases in swiprosin-1 in HRGECsincubated with HG3.體內(nèi)研究 Ruboxistaurin (LY333531; 1 mg/kg/d for 8 weeks) markedly reduces GEC apoptosis as well as swipro

10、sin-1 upregulation, and ameliorates renal glomerular injury in the diabetic mice. Ruboxistaurin also potently attenuates the expression of PARP, cleaved-caspase9, cleaved-caspase3, and the Bax/Bcl-2 ratio, in diabetic mice3. Ruboxistaurin(LY333531; 0.1, 1.0, or 10.0 mg/kg/d, po.o.) dramatically redu

11、ces the number of leukocytes trapped in the retinalmicrocirculation of diabetic rats4.PROTOCOLCell Assay 2 The second passages of human umbilical vein endothelial cells (HUVEC) are grown to confluence in microtiterplates coated with gelatin. The medium contains 5.5 mM glucose. If endothelial cells a

12、re stimulated with 27.7 mMglucose for 4 days, they are seeded in the well at a calibrated higher cell concentration in order to achievecomparable cell density at the day adhesion assays are performed. Therefore, cell density in the wells is testedthoroughly in control wells of each glucose concentra

13、tion prior to monocyte adhesion assays. If Ruboxistaurin isused in this assay, it is added to the cultures for the whole period2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Rats4Administration 4 Leukocyte entrapment is evaluated only once aft

14、er a 4-week diabetic period in both groups of rats with and withoutRuboxistaurin treatment, using one eye (right eye) of each rat. Ruboxistaurin is administered orally at dosages of 0.1Page 2 of 3 www.MedChemE(n = 8), 1.0 (n = 16), and 10.0 mg/kg/d (n = 8) for 4 weeks, from the time streptozotocin i

15、s injected in the rats4.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. Endocrinology. 2018 May 1;159(5):2253-2263. Diabetes Metab Syndr Obes. 2019 Nov 4;12:2289-2302. Biosci Rep. 2018 Sep

16、7;38(5).See more customer validations on HYPERLINK www.MedChemE 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(2H)-d ione (LY333531) and related analogues: isozyme s

17、elective inhibitors of protein kinase C beta. 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 human monocytes toendothelial cells in vitro. J Diabetes Sci Technol. 2007 Nov;1(6):929-35

18、.3. Wang ZB, et al. LY333531, a PKC inhibitor, attenuates glomerular endothelial cell apoptosis in the early stage of mouse diabetic nephropathy 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 microcirculation of diabetic r