氨基核苷嘌呤霉素作用机制 - Medchemexpress - MCE中国

1、Product Data SheetPuromycin aminonucleosideCat. No.: HY-15695CAS No.: 58-60-6分式: CHNO分量: 294.31作靶点: Bacterial; Apoptosis; Dipeptidyl Peptidase; Aminopeptidase作通路: Anti-infection; Apoptosis; Metabolic Enzyme/Protease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 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制备储备液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；旦配成溶液，请分装保存，避免反

3、复冻融造成的产品失效。储备液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 储存时，请在 6 个内使，-20C 储存时，请在 1 个内使。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。以下溶解案都请先按照 In Vitro 式配制澄清的储备液，再依次添加助溶剂：为保证实验结果的可靠性，澄 的储备液可以根据储存条件，适当保存；体内实验的作液，建议您现现配，当天使； 以下溶剂前显的百分 指该溶剂在您配制终溶液中的体积占；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的式助溶1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5%

4、 Tween-80 45% salineSolubility: 2.08 mg/mL (7.07 mM); Clear solution此案可获得 2.08 mg/mL (7.07 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 20.8 mg/mL 的澄 DMSO 储备液加到 400 L PEG300 中，混合均匀；向上述体系中加50 L Tween-80，混合均匀；然后继续加 450 L 理盐定容 1 mL。2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.08 mg/mL (7.07 mM

5、); Clear solutionPage 1 of 2 www.MedChemE此案可获得 2.08 mg/mL (7.07 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 20.8 mg/mL 的澄 DMSO 储备液加到 900 L 20% 的 SBE-CD 理盐溶液中，混合均匀。3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.08 mg/mL (7.07 mM); Clear solution此案可获得 2.08 mg/mL (7.07 mM，饱和度未知) 的澄 溶液，此案不适于实验周 期在半个以上的实验。以 1

6、mL 作液为例，取 100 L 20.8 mg/mL 的澄 DMSO 储备液加到 900 L 油中，混合均匀。BIOLOGICAL ACTIVITY物活性 Puromycin aminonucleoside (NSC 3056)种氨 核苷类抗素，为嘌呤霉素类似物1。Puromycinaminonucleoside 诱导细胞凋亡 (apoptosis)2。Puromycin aminonucleoside 可逆抑制肽基肽酶 (dipeptidylpeptidase II) 和胞浆丙氨酸氨基肽酶3。体外研究 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.体内研究 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