氨基核苷嘌呤霉素作用機制 - Medchemexpress - MCE中國

1、Product Data SheetPuromycin aminonucleosideCat. No.: HY-15695CAS No.: 58-60-6分式: CHNO分量: 294.31作靶點: Bacterial; Apoptosis; Dipeptidyl Peptidase; Aminopeptidase作通路: Anti-infection; Apoptosis; Metabolic Enzyme/Protease儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 H2O :

2、 33.33 mg/mL (113.25 mM; Need ultrasonic)DMSO : 32 mg/mL (108.73 mM)* means soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 3.3978 mL 16.9889 mL 33.9778 mL5 mM 0.6796 mL 3.3978 mL 6.7956 mL10 mM 0.3398 mL 1.6989 mL 3.3978 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；旦配成溶液，請分裝保存，避免反

3、復凍融造成的產(chǎn)品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲存時，請在 6 個內(nèi)使，-20C 儲存時，請在 1 個內(nèi)使。體內(nèi)實驗請根據(jù)您的實驗動物和給藥式選擇適當?shù)娜芙獍浮Ｒ韵氯芙獍付颊埾劝凑?In Vitro 式配制澄清的儲備液，再依次添加助溶劑：為保證實驗結果的可靠性，澄 的儲備液可以根據(jù)儲存條件，適當保存；體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當天使； 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；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的式助溶1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5%

4、 Tween-80 45% salineSolubility: 2.08 mg/mL (7.07 mM); Clear solution此案可獲得 2.08 mg/mL (7.07 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 20.8 mg/mL 的澄 DMSO 儲備液加到 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. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.08 mg/mL (7.07 mM

5、); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.08 mg/mL (7.07 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 20.8 mg/mL 的澄 DMSO 儲備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合均勻。3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.08 mg/mL (7.07 mM); Clear solution此案可獲得 2.08 mg/mL (7.07 mM，飽和度未知) 的澄 溶液，此案不適于實驗周 期在半個以上的實驗。以 1

6、mL 作液為例，取 100 L 20.8 mg/mL 的澄 DMSO 儲備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Puromycin aminonucleoside (NSC 3056)種氨 核苷類抗素，為嘌呤霉素類似物1。Puromycinaminonucleoside 誘導細胞凋亡 (apoptosis)2。Puromycin aminonucleoside 可逆抑制肽基肽酶 (dipeptidylpeptidase II) 和胞漿丙氨酸氨基肽酶3。體外研究 Puromycin aminonucleoside (NSC 3056) (30 g/mL

7、) markedly increases p53 protein levels in podocytes. Puromycinaminonucleoside (NSC 3056)-induced podocyte apoptosis is p53 dependent. Puromycin aminonucleoside (NSC 3056)induces podocyte apoptosis in a time-dependent manner2. The IC50 values for PMAT-expressing and vector-transfected cells are 48.9

8、 and 122.1 M, respectively, suggesting expression of PMAT-enhanced cell sensitivity toPuromycin aminonucleoside. Puromycin aminonucleoside (NSC 3056) (250 M) is toxic to both PMAT-expressing andvector-transfected cells. Puromycin aminonucleoside (NSC 3056) uptake in PMAT-expressing cells is fourfold

9、 higher atpH 6.6 than that at pH 7.44.體內(nèi)研究 The number of podocytes per glomerulus is 95.517.6 in the control rats, 90.7 on Day 4 in Puromycinaminonucleoside (NSC 3056) (8 mg/100 g, i.v.)-treated nephrosis rats. The amount of nephrin per glomerulus incontrol rats is 1.020.11 fmol and those in Puromyc

10、in aminonucleoside (NSC 3056) nephrosis rats are reduced to0.460.06 fmol and 0.350.04 fmol on Day 4 and Day 7. The nephrin amount per podocyte is significantly decreasedassociation with the development of proteinuria in Puromycin aminonucleoside (NSC 3056) nephrosis rats5. Ratsgiven Puromycin aminon

11、ucleoside (NSC 3056) (100 mg/kg, s.c.) gain less weight and their serum creatinine levels arehigher than the control rats6.PROTOCOLCell Assay 4 Cells are seeded in MEM with 10% FBS on 96-well plates at a density of 5,000 cells/well. After appr 48-h incubation(appr 40-50% confluence), cells are chang

12、ed to fresh growth medium containing Puromycin aminonucleoside (NSC3056) at various concentrations. For the protection experiment, cells are incubated in medium containing 250 MPuromycin aminonucleoside (NSC 3056) with or without the PMAT inhibitor decynium-22 (2 M). After a total of 72-hincubation

13、in a 95% O2 incubator at 37C, cells are washed and the plates. The IC50 values are determined by fittingthe cell growth data to the following model using nonlinear regression (WinNonLin version 3.2): S=Smax Smax S0 C/(C + IC50), where S is the cell survival expressed as percentage of the optical den

14、sity to untreated controlcells, Smax is the maximal cell survival, S0 is the lowest residual cell survival at the high drug concentration, C isPuromycin aminonucleoside concentration, is the Hill coefficient, and IC50 is the Puromycin aminonucleosideconcentration leading to half-maximal cell surviva

15、l. Five to six determinations are carried out within each experiment,and four independent experiments are performed.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Male F344 rats at 11 weeks of age are purchased from JaPuromycin aminonucleoside S

16、LC. Normal rats and aAdministration 5 Puromycin aminonucleoside nephrosis model are used in the present study. Puromycin aminonucleoside (NSC 3056)Page 2 of 3 www.MedChemEnephrosis is induced in rats by a single intravenous injection of Puromycin aminonucleoside at a dose of 8 mg/100 gbody weight in

17、 saline. Control animals receive an identical volume of saline. Nephrotic rats (n=6 per group) arestudied at Days 4 and 7 after the Puromycin aminonucleoside injection.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Wada T, et al. Prevents

18、podocyte apoptosis induced by puromycin aminonucleoside: role of p53 and Bcl-2-related family proteins. J Am Soc Nephrol.2005 Sep;16(9):2615-25.2. Xia L, et al. Podocyte-specific expression of organic cation transporter PMAT: implication in puromycin aminonucleosidenephrotoxicity. Am J PhysiolRenal

19、Physiol. 2009 Jun;296(6):F1307-13.3. Kawakami H, et al. Dynamics of absolute amount of nephrin in a single podocyte in puromycin aminonucleoside nephrosis rats calculated byquantitative glomerular proteomics approach with selected reaction monitoring mode. Nephrol Dial Transplant. 2012 Apr;4. Nosaka K, et al. An adenosine deaminase inhibitor prevents puromycin aminonucleoside nephrotoxicity. Free Radic Biol Med 1