1、n and body protection Impervious clothing.Respiratory protection Suitable respirator.Environmental exposure controlsKeep the product away from drains, water courses or the soil. Cleanspillages in a safe way as soon as possible.9. PHYSICAL AND CHEMICAL PROPERTIES9.1 Information on basic physical and
2、chemical propertiesAppearance White to yellow (Solid)Odor No data availableOdor threshold No data availablepH No data availableMelting/freezing point No data availableBoiling point/range No data availableFlash point No data availableEvaporation rate No data availableFlammability (solid, gas) No data
3、 availableUpper/lower flammability or explosive limitsNo data availableVapor pressure No data availableVapor density No data availableRelative density No data availableWater Solubility No data availablePartition coefficient No data availableAuto-ignition temperature No data availableDecomposition te
4、mperature No data availableViscosity No data availableExplosive properties No data availableOxidizing properties No data available9.2 Other safety informationNo data available.10. STABILITY AND REACTIVITY10.1 ReactivityNo data available.10.2 Chemical stabilityStable under recommended storage conditi
5、ons.10.3 Possibility of hazardous reactionsPage 3 of 5 www.MedChemENo data available.10.4 Conditions to avoidNo data available.10.5 Incompatible materialsStrong acids/alkalis, strong oxidising/reducing agents.10.6 Hazardous decomposition productsUnder fire conditions, may decompose and emit toxic fu
6、mes.Other decomposition products - no data available.11.TOXICOLOGICAL INFORMATION11.1 Information on toxicological effectsAcute toxicityClassified based on available data. For more details, see section 2Skin corrosion/irritationClassified based on available data. For more details, see section 2Serio
7、us eye damage/irritationClassified based on available data. For more details, see section 2Respiratory or skin sensitizationClassified based on available data. For more details, see section 2Germ cell mutagenicityClassified based on available data. For more details, see section 2CarcinogenicityIARC:
8、 No component of this product present at a level equal to or greater than 0.1% is identified as probable, possible orconfirmed human carcinogen by IARC.ACGIH: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmedcarcinogen by ACGIH.NT
9、P: No component of this product present at a level equal to or greater than 0.1% is identified as a anticipated or confirmedcarcinogen by NTP.OSHA: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmedcarcinogen by OSHA.Reproductive t
10、oxicityClassified based on available data. For more details, see section 2Specific target organ toxicity - single exposureClassified based on available data. For more details, see section 2Specific target organ toxicity - repeated exposureClassified based on available data. For more details, see sec
11、tion 2Aspiration hazardClassified based on available data. For more details, see section 212. ECOLOGICAL INFORMATION12.1 ToxicityNo data available.12.2 Persistence and degradabilityNo data available.12.3 Bioaccumlative potentialNo data available.12.4 Mobility in soilNo data available.Page 4 of 5 www
12、.MedChemE12.5 Results of PBT and vPvB assessmentPBT/vPvB assessment unavailable as chemical safety assessment not required or not conducted.12.6 Other adverse effectsNo data available.13. DISPOSAL CONSIDERATIONS13.1 Waste treatment methodsProductDispose substance in accordance with prevailing countr
13、y, federal, state and local regulations.Contaminated packagingConduct recycling or disposal in accordance with prevailing country, federal, state and local regulations.14. TRANSPORT INFORMATIONDOT (US)This substance is considered to be non-hazardous for transport.IMDGThis substance is considered to
14、be non-hazardous for transport.IATAThis substance is considered to be non-hazardous for transport.15Bay 60-7550Cat. No.: HY-14992CAS No.: 439083-90-6Molecular Formula: CHNOMolecular Weight: 476.57Target: Phosphodiesterase (PDE)Pathway: Metabolic Enzyme/ProteaseStorage: Powder -20C 3 years4C 2 yearsI
15、n solvent -80C 6 months-20C 1 monthSolvent significant increases are observed at a dose of 3 mg/kg. In nonstressed mice, Bay 60-7550 increases, in a dose-dependent manner, the number of head-dips and time spent head-dipping, compared with vehicle-treated mice; significant increases are observed at d
16、oses of 1 and 3 mg/kg1.PROTOCOLKinase Assay 1 COS-7 cells are maintained in complete DMEM (containing 10% fetal calf serum, 100 units/mL penicillin G, 100 mg/mL streptomycin, and 400 M L-alanyl-L-glutamine) at 37C in 5% CO2 atmosphere. A PDE2 expression plasmid is introduced into COS-7 cells using t
17、he FuGENE6 transfection reagent. Cells are lysed in solubilization buffer (275 mM NaCl, 1.5 mM MgCl2, 2 mM EGTA, 2% Triton X, 20% glycerol, and 40 mM Tris-HCl), and the cell lysates are used in the immunoprecipitation procedures. A protein A-agarose bead slurry (100 L) is washed three times with ice
18、-cold phosphate-buffered saline (100 mM NaCl, 2.7 mM KCl, 10.6 mM Na2HPO4, and 1.6 mM NaH2PO4) and mixed with the 5 g of PDE2 antibody and 100 L (2 g/L) of the lysate sample and rotated overnight at 4C. The bead/sample mixture is then centrifuged at 1000g to separate the beads from the supernatant.
19、The beads are resuspended in 100 L of ice-cold lysis buffer (20 mM Tris, pH 7.4, 140 mM NaCl, 0.75 mM MgCl2, 1 mM EGTA, 1% Triton X-100, and 20% glycerol, containing protease and phosphatase inhibitors) to elute the PDE2 for use in the enzyme activity assays. The PDE2 activity assay is done. The rec
20、ombinant PDE2 enzyme derived from COS-7 cell expression and diluted in KHEM buffer (50 mM KCl, 50 mM HEPES, 10 mM EGTA, and 1.9 mM MgCl2, pH 7.2) is mixed with different concentrations of PDE2 inhibitors (Bay 60-7550, ND7001, and EHNA) and 3HcGMP/cGMP (5 M) as the substrate. The mixture is then incu
21、bated for 30 min at 37C (100 L of reaction volume). To convert the 3HGMP to 3Hguanosine, samples are incubated with snake venom from Crotalus atrox for 30 min at 37C. The samples are then vortexed with a freshly prepared slurry of Dowex/water/ethanol 1:1:1, v/v and then centrifuged for 10 min. 3HGua
22、nosine in the supernatant is then quantified by liquid scintillation counting. Bay 60-7550 is dissolved in dimethyl sulfoxide, EHNA is dissolved in distilled water, and ND7001 is dissolved in ethanol as 10 mM stocks and then diluted for use in assays with 20 mM Tris, pH 7.4; final concentrations of
23、the respective solvents did not affect the assay. IC50 values at a single substrate concentration are determined by nonlinear regression analysis of the log concentration-response curves for each PDE2 inhibitor; Ki values are calculated1.MCE has not independently confirmed the accuracy of these meth
24、ods. They are for reference only.Cell Assay 2 Growth of human distal pulmonary artery smooth muscle cells isolated from patients with idiopathic pulmonary arterial hypertension (IPAH) or control cells from adults undergoing transplant or lung resection for suspected malignancy, are monitored followi
25、ng treatment with BAY 60-7550 (1 M), ANP (1 M), DETA-NONOate (10 M), or Treprostinil (1 M), alone or in combination2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Administration 1Mice1 Male ICR mice weighing 28 to 35 g are used. Bay 60-7550 (0.
26、5, 1, and 3 mg/kg), ND7001 (0.5, 1.0, and 3 mg/kg), Detanonoate (0.5 mg/kg), L-NAME (50 mg/kg), or Diazepam (1 mg/kg) is administered after restraint stress and 30 min before behavioral testing. Mice also are treated with Bay 60-7550 (3 mg/kg), ND7001 (3 mg/kg), Detanonoate, (0.5 mg/kg), L-NAME (50
27、mg/kg), or diazepam (1 mg/kg) in the absence of restraint stress; drugs are administered 30 min before the behavioral tests. Bay 60-7550 shows 50-fold selectivity for PDE2 compared with PDE1, 100-fold compared with PDE5, and greater than 200-fold compared with the other PDE families. ND7001 exhibits
28、 at 1east 100-fold selectivity for inhibition of PDE2 relative to other PDE families. For antagonism tests to assess the role of cGMP signaling in the behavioral effects of the PDE2 inhibitors, ODQ, an inhibitor of soluble guanylyl cyclase (20 mg/kg), is administered 20 min before Bay 60-7550 or ND7
29、001.MCE has not independently confirmed the accuracy of these methods. They are for reference only.www.MedChemE2CUSTOMER VALIDATIONSee more customer validations on www.MedChemEREFERENCES1. Masood A, et al. Anxiolytic effects of phosphodiesterase-2 inhibitors associated with increased cGMP signaling.
30、 J Pharmacol Exp Ther. 2009 Nov;331(2):690-9.2. Bubb KJ, et al. Inhibition of phosphodiesterase 2 augments cGMP and cAMP signaling to ameliorate pulmonary hypertension. Circulation. 2014 Aug 5;130(6):496-507.Caution: Product has not been fully validated for medical applications. For research use onl
31、y.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: techMedChemEAddress: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA Psychopharmacology (Berl). 2018 Jun 7.www.MedChemE3了。儿们一 接一 止了唱。最 ，连 和 了。可要 了，留 的森林上空突 来了轻轻的 ：”尔科，”尔科，好了好了 猎人一惊。 到了 上，一动 动， 来的 呢 ”尔科，”尔科，好了好了 ”尔科，”尔科 是一 森林的上空，“ 长 急匆匆扇 。一 另一 是
32、打 。是 ，的是雌的， 的是雄的。 的那 ， 车 一样，fl转，到了currency1里。猎人 一样了过：他 ，晚了， currency1的儿到currency1里，那 白费夫了。， 的羽毛和树叶一样 的。它挂currency1上，一 到了。那， 儿又 来了”尔科，”尔科 的 。太远了散打 到。猎人又靠 ， “ 。森林里好 ”尔科，”尔科 好了好了 叫 新了来。那，那太远了扔个什 东西， 它吸引过来，应该可以的 第一部分 森林报：春 第11节：冬眠苏醒月(11)猎人 ，向空中fi。雄 ，它正fl的森林薄 里 自 的爱人雌 。 一个黑糊糊的东西 来，又了 。是雌 它空中转了个 ，向 直接猎人的方向。猎人的 动了。 打 最好 过一“ 准 了 来。-|-|-|-|-|1 1.176 MM R 0.0144 5.49910 6.37950 0.51742 1.222 MM R 0.0156 1053.68909 1126.73889 99.13613 1.315 MF R 0.0157 2.81441 2.98392 0.26484 1.328 FM R 9.15e-3 8.68180e-1 1.58062 0
