1、ClofibrateCat. No.: HY-B0287CAS No.: 637-07-0Molecular Formula: CHClOMolecular Weight: 242.7Target: PPARPathway: Cell Cycle/DNA DamageStorage: Pure form -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 monthSolvent PPAR, EC50: 500 MIn Vitro Clofibrate is a PPAR agonist, with E50s of 50 M, null50
2、0 M for murine PPAR and PPAR, and 55 M, null500 M for human PPAR and PPAR, respectively1. Clofibrate (0.5, 1, 2 mM) increases FABP1 expression in two fatty acid (FA)-treated rat hepatoma cells. Clofibrate lowers ROS levels after early treatment, much more than late treatment in FA-treated cells2.In
3、Vivo Clofibrate (0.5%) up-regulates serum concentrations and hepatic expression of FGF21 in fetuses, with a return to basal levels after Clofibrate administration withdrawal. Clofibrate administration-offspring have significantly higher expression of thermogenic genes (Ucp1, Cidea, Ppara Ppargc1a, C
4、pt1b) and UCP1 protein levels in response to HFD in inguinal fat, but not in retroperitoneal (combined with perirenal) or epididymal fat3.Product Data Sheet InhibitorsAgonistsScreening Librarieswww.MedChemE1PROTOCOLCell Assay 1 Cells are seeded at a density of 2.5 104 cells/well (for WST-1, intracel
5、lular lipid droplet quantification and dichlorofluorescein (DCF) assay, 96-well plates) and 1 105 cells/well (for Nile Red Staining, 12-well plates) in MEM/EBSS medium and incubated overnight for adherence. The next day cell culture medium is replaced with freshly prepared medium containing the fatt
6、y acid mixture oleate:palmitate (2:1) in presence of 3% fatty-acid-free bovine serum albumin. Cells are treated with 0, 0.5, 1, 2, and 3 mM fatty acid (FA) mixture for 24 and 48 hr at 37C in a humidified incubator in an atmosphere of 95% air and 5% CO2. Clofibrate is used to increase levels of FABP1
7、 in treated cell cultures. Clofibrate (500 M) is dissolved in DMSOand later added to the medium (DMSO 0.1% v/v in final volume). Control cells are incubated with DMSO alone. Four different cell treatments includ 1-day FA treatment, 2-day FA treatment, early clofibrate intervention and late clofibrat
8、e intervention1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Administration 3Female and male C57BL/6JNarl mice are used for breeding. Females with parity from 1 to 5 are used. Pregnant females are fed either a control (C) or experimental (CF)
9、diet from breeding to parturition. The C diet is based on an AIN-93M diet with a slight modification to contain 21 kcal% fat from soybean oil, whereas the CF diet is the C diet with addition of 0.5% clofibrate. Pregnancy is dated by the presence of a vaginal plug (defined as pregnancy day 1). After
10、spontaneous parturition (pregnancy day 19.5 0.5), all littermates are uniformly nursed by dams fed the C diet for 3 wk, with litter sizes adjusted to 8-10, weaned onto a nonpurified standard diet for 4 wk, and then switched to a HFD (51 kcal% fat, butter-based) for 5 wk. In this study, only male off
11、spring are used and 2 groups of offspring are designated, according to their mothers diet (C or CF). All mice are kept in a room maintained at 23 2C, with a controlled 12-h-light:-dark cycle with ad libitum to feed and drinking water. Body weight and feed intake are recorded weekly3.MCE has not inde
12、pendently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Willson TM, et al. The PPARs: from orphan receptors to drug discovery. J Med Chem. 2000 Feb 24;43(4):527-50.2. Chen Y, et al. Clofibrate Attenuates ROS Production by Lipid Overload in Cultured Rat Hepatoma Ce
13、lls. J Pharm Pharm Sci. 2017;20(0):239-251.3. Chen SH, et al. Prenatal PPAR activation by clofibrate increases subcutaneous fat browning in male C57BL/6J mice fed a high-fat diet during adulthood. PLoS One. 2017 Nov 2;12(11):e0187507.Caution: Product has not been fully validated for medical applErdo
14、steineCat. No.: HY-B0289CAS No.: 84611-23-4Molecular Formula: CHNOSMolecular Weight: 249.31Target: NF-BPathway: NF-BStorage: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 monthSolvent group 2, Erdosteine-treated; group 3, Methotrexate (MTX)-treated; and group 4, Methotrexate+Erdosteine
15、 treated. On the first day of experiment, a single dose of Methotrexate is intraperitoneally administered to groups 3 and 4, although a daily single dose of Erdosteine is orally administered to group 2 and 4 for 7 days. At the end of the experiment, the testes of the animals are removed and weighed.
16、 The levels of total antioxidant capacity and total oxidative stress, and myeloperoxidase activity in the Methotrexate group are higher than the control group (p0.05). Lipid peroxidation levels are not changed in Methotrexate group compared with control group. In conclusion, Erdosteine can effective
17、ly protect the testes in Methotrexate-induced toxicity. Erdosteine administration with Methotrexate improves testicular injures, as indicated by appearance of spermatogenesis in seminiferous tubules2.PROTOCOLCell Assay 1 The murine macrophage/monocyte cell line RAW264.7 are maintained as monolayers
18、in Dulbeccos modified Eagles medium (DMEM) containing 10 % fetal bovine serum, 60 U/mL Penicillin, and 100 g/mL Streptomycin at 37.8C in 5 % CO2. The cell viability is quantified using a colorimetric tetrazolium compound MTS assay. Briefly, 1104 cells incubated with various concentrations of Erdoste
19、ine (1, 10, or 100 g/mL) for 24 h are treated with 10 L of MTS solution (5 mg/mL) for 45 min. The cells are then lysed with isopropyl alcohol, and the absorbance is read at the wavelength of 540 nm1. MCE has not independently confirmed the accuracy of these methods. They are for reference only.Anima
20、l Administration 2Mice2 Twenty-six male C57BL/6 mice (8 weeks, 20-30 g) are randomly divided into four groups. In control group (n=6); mice are treated the 0.5 mL of saline as a placebo intraperitoneally (i.p.). In Erdosteine group (n=6), mice are treated with Erdosteine orally (gavage; 10 mg/kg) fo
21、r 7 days. In this study, low-dose MTX are used because high-dose (20-40 mg/kg) MTX has anti-inflammatory and immunosuppressive activity. Mice in MTX group (n=7) are injected with single dose of i.p. MTX (10 mg/kg). In MTX+Erdosteine group (n=7), mice are injected with single dose of i.p. MTX (10 mg/
22、kg) the first day and Erdosteine is given orally (10 mg/kg) to the animals starting the first day for 7 days. After the last administration of the drug, all rats fasted about 12 hours, but have free access to water. And then, the animals are sacrificed by cervical dislocation at the end of the exper
23、iment. Following sacrifice, the testes are quickly removed from the mice. Right testes specimens are fixed in 10% neutral-buffered formaldehyde solution for histological assessment2. MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Park JS,
24、et al. Anti-inflammatory Effect of Erdosteine in Lipopolysaccharide-Stimulated RAW 264.7 Cells. Inflammation. 2016 Aug;39(4):1573-81.2. Oktar S, et al. Beneficial effect of erdosteine on methotrexate-induced testicular toxicity in mice. Toxicol Ind Health. 2010 Aug;26(7):433-8.www.MedChemE2Caution:
25、Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: techMedChemEAddress: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USAwww.MedChemE3抖鎂殅蔲抖鎇殅蔲鎂檅薭腠鎇檅薭灐賟牁嘃旽蝙薓梅脎牁嘄柽舉薓殅脕爀鎇殅蔕鎂斅薌豥鎇斅薌豥Clonidine hydrochlorideCat. No.: HY-B
26、0409ACAS No.: 4205-91-8Molecular Formula: CHClNMolecular Weight: 266.55Target: Adrenergic ReceptorPathway: GPCR/G ProteinStorage: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 monthSolvent Need ultrasonic and warming)ConcentrationSolvent Mass 1 mg 5 mg 10 mg1 mM 3.7516 mL 18.7582 mL 37
27、.5164 mL5 mM 0.7503 mL 3.7516 mL 7.5033 mLPreparing Stock Solutions10 mM 0.3752 mL 1.8758 mL 3.7516 mLPlease refer to the solubility information to select the appropriate solvent.BIOLOGICAL ACTIVITYDescription Clonidine hydrochloride is an agonist of 2-adrenoceptor and potent antihypertensive agent.
28、In Vitro Clonidine (0.01, 0.1 or 1 M) significantly induces CGRP ( and ) mRNA expression in a dose-dependent manner in endothelial cells. Clonidine treatment (1 M) for 24 h significantly increases the NO level in endothelial cells. NO pathway modulates CGRP production induced by clonidine2.Clonidine
29、 (50 g/kg, i.p.) induces a significant decrease in body temperature of rat lasting 3 hr, with the maximum at 1 hr after administration. An intracerebroventricular pretreatment of rats with neutral doses of phentolamine 15 min before clonidine considerably antagonizes the clonidine-induced hypothermi
30、a1. Clonidine (0.003-0.05 mg/kg, i.p.) potently suppresses dopamine efflux in the prefrontal cortex induced by PCP. Pretreatment with the alpha-2A receptor antagonist (BRL-44408) prevents clonidine from suppressing PCP-induced dopamine overflow in the prefrontal cortex3. In DMSO-pretreated SO rats,
31、clonidine (0.6 g i.c.) has no effect on blood pressure. However, after central adenosine A1R blockade (DPCPX) in SO rats, clonidine significantly (P 0.05, one-way ANOVA) clonidine-evoked reduction in blood pressure in ABD rats. In DPCPX-pretreated SO rats and along with the appearance of the hypoten
32、sive response, clonidine causes a significant (P 0.05) increase in the RVLM pERK1/2 level compared with basal or clonidine treatment in DMSO-pretreated SO rats. In vehicle (DMSO)-pretreated ABD rats, clonidine significantly (P 0.05) enhances RVLM pERK1/2, and this response is not affected by DPCPX p
33、retreatment4.PROTOCOLAnimal Administration 3On the day of the experiment, the flow rate is increased to 2 L/min approximately 2 h before beginning the collection of baseline samples. Dialysates are collected every 20 min; after 4 baseline samples are collected, animals are pretreated with an intra-p
34、eritoneal (i.p.) injection of either 0.9% saline (the vehicle), clonidine (0.0033, 0.01 or 0.05 mg/kg) or guanfacine (0.05 or 0.5 mg/kg), before receiving an injection of PCP (2.5 mg/kg, i.p.) 20 min later. In a separate study, BRL (1.0 mg/kg) is administered 20 min prior to clonidine. In addition,
35、for some control experiments, the animals only receive one injection of saline, clonidine (0.01 or 0.05 mg/kg), guanfacine (0.5 mg/kg) or BRL (1.0 mg/kg).MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Bugajski J, et al. The involvement of
36、central alpha-adrenergic and histamine H2-receptors in the hypothermia induced by clonidine in the rat. Neuropharmacology. 1980 Jan;19(1):9-15.2. Zhang YM, et al. Clonidine induces calcitonin gene-related peptide expression via nitric oxide pathway in endothelial cells. Peptides. 2009 Sep;30(9):1746
37、-52.3. Jentsch JD, et al. Clonidine and guanfacine attenuate phencyclidine-induced dopamine overflow in rat prefrontal cortex: mediating influence of the alpha-2A adrenoceptor subtype. Brain Res. 2008 Dec 30;1246:41-6.4. Nassar N, et al. Brainstem adenosine A1 receptor signaling masks phosphorylated
38、 extracellular signal-regulated kinase 1/2-dependent hypotensive action of clonidine in conscious normotensive rats. J Pharmacol Exp Ther. 2009 Jan;328(1):83-9.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 提出了相应的计量方法，其中包括：标准法、高级计量法等。此外，国外针对于方面的研究较为广泛，其中涉及到了电子、结算、运营质量风险等。进入到21世纪，便有众多学者纷纷表示与其他融资方式进行对比与分析后，能够清晰的看出融资租赁的所存在的优势是非常显著的，不但能够对经济的增长具有促进作用，同时在投资方面的作用也是不可小视的。美国设备租赁协会的James Renner在美国租赁业市场回顾中提到现在融资租赁已进入了一个新的阶段，一个挑战不亚于机遇的阶段。在经济仍然保持强势的同时，其业务的特点是凭借令人难以置信的竞争以及客户基础，向全球成熟的承租人转移，但是也有通过营销上和技术上的变化所带来的机遇。
