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MG-132_DataSheet_MedChemExpress

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Inhibitors, Agonists, Screening Librarieswww.MedChemExpress.comData Sheet

BIOLOGICAL ACTIVITY: MG–132 is a potent, non–specific 20S proteasome inhibitor, with IC50 of 24.2 nM for the β5 chymotrypsin–like active site.IC50 & Target: IC50: 24.2 nM (chymotrypsin–like activity)[1]In Vitro: Dose–dependent inhibition of cell growth is observed in HeLa cells with an IC50 of approximately 5 μM MG132 for 24 h.MG132 inhibits the growth of HeLa cells via inducing the cell cycle arrest as well as triggering apoptosis[2]. MG–132 inhibits C6glioma cell proliferation in a time– and dose–dependent manner (the IC50 value at 24 h is 18.5 μM). MG–132 (18.5 μM) suppressesthe proteasome activity by about 70% at 3 h. MG–132 induces apoptosis via down–regulation of antiapoptotic proteins Bcl–2 andXIAP, up–regulation of pro–apoptotic protein Bax and caspase–3, and production of cleaved C–terminal 85 kDa PARP. MG–132 alsocauses a more than 5–fold increase of reactive oxygen species[3]. The IC50 of MG–132 against HeLa, CaSki, and C33A cervical cancercells viability after 48 h of incubation is 2.1, 3.2, and 5.2 μM, respectively[4].In Vivo: The in vivo antitumor activity of MG–132 against cervical cancer is examined using s.c. xenograft models. MG–132 isinjected at 1 mg/kg using the following schedule: days 1, 4, 8, 12, 15 18, 23, and 26 for mice bearing HeLa tumors. The growthinhibition rates of MG132 compared to control is 49%[4]. MG–132 (i.p., 0.1 mg/kg/day) attenuates pressure–overload–inducedcardiac hypertrophy and improves cardiac function in abdominal aortic banding (AAB) rats through regulation of ERK1/2 and JNK1signaling pathways[5].PROTOCOL (Extracted from published papers and Only for reference) Kinase Assay:[3]After growing on six–well plates (3×105 cells/well) for 24 h, C6 glioma cells are treated with either PBS (control) or18.5 μM MG–132 for 3, 6, 12, or 24 h at 37°C. Cells are thoroughly scraped from the culture dishes with a cell scraper and washedwith cold PBS. After centrifugation for 10 min at 800×g, the cell pellets are suspended in ice–cold buffer (50 mM Tris–HCl, pH 7.5, 20μM ATP, 5 mM MgCl2, 1 mM dithiothreitol, and 20% glycerol) and homogenized with a Pyrex glass microhomogenizer (20 strokes).The homogenate is centrifuged at 15 000×g for 10 min at 4°C to obtain supernatant. Protein concentration is determined usingprotein assay kits. A total of 10 μL (1 μg/μL) of each freshly made supernatant is incubated in a 96–well plate at 37°C for 30 minwith 10 μL of 300 μM of Succinyl–LLVY–AMC and 85 μL of assay buffer (20 mM Tris–HCl, pH 7.5, and 20% glycerol). Release offluorescent AMC is measured with a spectrofluorometer at 440 nm with an excitation wavelength of 380 nm[3].Cell Assay: MG–132 is dissolved in PBS to a storage concentration of 50 μM[3]. [3]C6 glioma cells are seeded onto 96–well microplates(3×104 cells/well) and cultured for 24 h. The cells are treated with PBS or MG–132 final concentrations of 10, 20, 30, and 40 μM,respectively. Cell viability is assessed using an MTT assay at 3, 6, 12, and 24 h after MG–132 treatment. The absorbance value at 570nm is read using an automatic multi–well spectrophotometer. C6 glioma cells (3×105 cells/well) are allowed to grow on coverslipsin 6–well culture plates for 24 h. The cells are then treated with either PBS (control) or 18.5 μM MG–132 at 37°C for 24 h. Cellsgrowing on glass coverslips are fixed in methanol for 5 min at room temperature. The fixed cells are washed twice with PBS andthen incubated with Hoechst 33342 for 5 min at room temperature and observed under a fluorescence microscope. Fragmented orProduct Name:MG–132Cat. No.:HY-13259CAS No.:133407-82-6Molecular Formula:C26H41N3O5Molecular Weight:475.62Target:ProteasomePathway:Metabolic Enzyme/ProteaseSolubility:10 mM in DMSO

www.MedChemExpress.comcondensed nuclei are scored as apoptotic[3].Animal Administration: MG–132 is dissolved in vehicle (saline) (Mice)[4].MG–132 is dissolved in vehicle (0.1% DMSO) (Rat)[5].[4][5]Mice[4]C.B–17/lcr–scid/scidJcl mice are inoculated s.c. with HeLa, CaSki, or C33A (1×107 cells). Tumors are allowed to grow for 1 week.Mice are killed and tumors are removed. Tumors are then cut into 2–mm diameter pieces and s.c. transplanted inC.B–17/lcr–scid/scidJcl mice (n=6 per group). One week after inoculation, mice are treated with i.v. injection of saline (control),MG–132 (1 mg/kg/dose) twice a week for 4 weeks. The volume (V) of tumors is measured before every injection, as estimated usingequation V=a×b2/2 where a and b are major and minor axes of the tumor measured by a caliper, respectively.Rat[5]Male Sprague–Dawley rats (8 weeks old, 180–230 g) are used to establish pressure–overload model. All animals are separated intofour groups (10 rats per group): (i) vehicle–treated sham group; (ii) MG–132–treated sham group; (iii) vehicle–treated abdominal aorticbanding (AAB) group; and (iv) MG–132–treated AAB group. Under intraperitoneal pentobarbital (50 mg/kg) anesthesia, AAB is createdusing a 5–0 suture tied twice around the abdominal aorta in which a 21–gauge needle is inserted. The needle is then retracted yieldinga 70–80% constriction with an outer aortic diameter of ~0.8 mm. In the sham surgery rats, the same surgery is performed except theaorta is constricted. At Day 3 after the surgery, MG–132–treated rats are intraperitoneally injected with 0.1 mg/kg/day of MG–132 for8 weeks. All control animals are injected with a corresponding volume of vehicle only (0.1% DMSO).References: [1]. Braun HA, et al. Tripeptide mimetics inhibit the 20 S proteasome by covalent bonding to the active threonines. J Biol Chem. 2005 Aug 5;280(31):28394–401.[2]. Han YH, et al. The effect of MG132, a proteasome inhibitor on HeLa cells in relation to cell growth, reactive oxygen species and GSH. Oncol Rep. 2009 Jul;22(1):215–21.[3]. Fan WH, et al. Proteasome inhibitor MG–132 induces C6 glioma cell apoptosis via oxidative stress. Acta Pharmacol Sin. 2011 May;32(5):619–25.[4]. Matsumoto Y, et al. Enhanced efficacy against cervical carcinomas through polymeric micelles physically incorporating theproteasome inhibitor MG132.Cancer Sci. 2016 Jun;107(6):773–81.[5]. Chen B, et al. MG132, a proteasome inhibitor, attenuates pressure–overload–induced cardiac hypertrophy in rats by modulation of mitogen–activatedprotein kinase signals. Acta Biochim Biophys Sin (Shanghai). 2010 Apr;42(4):253–8.

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PZM21_DataSheet_MedChemExpress

PZM21_DataSheet_MedChemExpress

Inhibitors, Agonists, Screening Data SheetBIOLOGICAL ACTIVITY: PZM21 is a potent and selective μ opioid receptor agonist with an EC50 of 1.8 nM.IC50 & Target: EC50: 1.8 nM (μ opioid receptor)[1]In Vitro: PZM21 has no detectable κOR or nociceptin receptor agonist activity–it is actually an 18 nM κOR antagonist–while it is a500–fold weaker δOR agonist, making it a selective μOR agonist. At hERG, PZM21 has an IC50 of between 2 and 4 μM, 500– to1,000–fold weaker than its potency as a μOR agonist. Signalling by PZM21 and other μOR agonists appears to be mediated primarilyby the heterotrimeric G protein Gi/o, as its effect on cAMP levels is eliminated by pertussis toxin and no activity is observed in acalcium release assay [1].In Vivo: PZM21 is a potent Gi activator with exceptional selectivity for μOR and minimal β–arrestin–2 recruitment. Unlike morphine,PZM21 is more efficacious for the affective component of analgesia versus the reflexive component and is devoid of both respiratorydepression and morphine–like reinforcing activity in mice at equi–analgesic doses. PZM21 displays dose–dependent analgesia in amouse hotplate assay, with a per cent maximal possible effect (% MPE) of 87% reached 15 min after administration of the highestdose of drug tested [1].PZM21 has a long–lasting analgesic effect on CNS mediated–pain responses, but does not cause respiratorydepression and constipation, two key side effects of opioid agonists. PZM21 does not exhibit the type of biomarker responses, suchas hyperlocomotion or conditioned place preference response, that are observed when morphine and other opioids are used andare associated with reinforcement and addiction[2].PROTOCOL (Extracted from published papers and Only for reference) Animal Administration:[1]Mouse: PZM21 is dissolved in 0.9% sodium chloride. Mice are injected with either vehicle, morphine (5mg/kg, or 10 mg/kg), TRV130 (1.2 mg/kg) or PZM21 (10 mg/kg; 20 mg/kg; or 40 mg/kg). After injection of drug, the analgesiceffect expressed as percentage maximum possible effect (%MPE) is measured at 15, 30, 60, 90 and 120 min after drug treatment[1].References: [1]. Manglik A, et al. Structure–based discovery of opioid analgesics with reduced side effects. Nature. 2016 Sep 8;537(7619):185–190.[2]. Kostic M, et al. Biasing Opioid Receptors and Cholesterol as a Player in Developmental Biology.Product Name:PZM21Cat. No.:HY-101386CAS No.:1997387-43-5Molecular Formula:C19H27N3O2SMolecular Weight:361.50Target:Opioid Receptor; Opioid ReceptorPathway:GPCR/G Protein; Neuronal SignalingSolubility:10 mM in DMSO

Menbutone_3562-99-0_DataSheet_MedChemExpress

Menbutone_3562-99-0_DataSheet_MedChemExpress

Product Name:Menbutone

CAS No.: 3562-99-0Product Data Sheet

Cat. No.:HY-B1136

MWt:258.27

Formula:C15H14O4

Purity :

>98%

Solubility:

Mechanisms:

Biological Activity: Pathways:Others; Target:Others

No data available

gyMenbutone is an oxobutyric acid derivative, and is a choleretic.Menbutone has a rapid onset ofaction, reaching its maximum plasma level within 1 hour and lasting for roughly 10 hours.

References:

Caution: Not fully tested. For research purposes only

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LY2109761_DataSheet_MedChemExpress

LY2109761_DataSheet_MedChemExpress

Inhibitors, Agonists, Screening Data SheetBIOLOGICAL ACTIVITY: LY2109761 is an orally active, selective TGF–β receptor type I/II (TβRI/II) dual inhibitor with Ki of 38 nM and 300 nM, respectively, andnegatively affects the phosphorylation of Smad2.IC50 & Target: Ki: 38 nM (TβRI), 300 nM (TβRII)In Vitro: LY2109761 significantly inhibits the growth of L3.6pl/GLT soft agar colonies in a dose–dependent manner, and results inappr 33% inhibition at 2 μM and 73% inhibition at 20 μM. Targeting TβRI/II kinase activity with LY2109761 (5 μM) almostcompletely suppresses both the basal and TGF–β1–stimulated migration of L3.6pl/GLT cells[1]. LY2109761 induces adose–dependent reduction in phosphorylation of Smad–2. HLE endogenous phosphorylation of Smad–2 is inhibited by LY2109761.LY2109761 blocks migration on different ECM proteins and invasion of both HLE and HLF through a 3–dimensional structure.LY2109761 increases E–cadherin mRNA expression after 24 hours and protein levels after 48 hours[2]. LY2109761 pretreatmentreduces clonogenic survival in cell cultures of U87MG and T98 following radiation, resulting in an increase in the radiosensitivitywith a DEF0.1 of 1.30 and 1.37, respectively[3].In Vivo: LY2109761 (50 mg/kg, p.o.) greatly reduces the tumor volume and increases the median survival duration of the mice to45.0 days. The mice treated with LY2109761 develop significantly fewer metastatic lesions and, in some of them, no metastaticlesion, as indicated by the GFP signal, can be identified in the abdomen[1]. LY2109761 enhances radiation–induced tumor growthdelay in a U87MG subcutaneous xenograft tumor model in BALB/c nude mice. LY2109761 increases survival in an orthotopical CSLCglioblastoma model and enhanced antitumor activity of radiation[2].PROTOCOL (Extracted from published papers and Only for reference) Cell Assay: LY2109761 is dissolved in 100% DMSO at a stock concentration of 10 mM.[1]L3.6pl/GLT cells are washed twice with coldPBS and lysed at 4°C into RIPA buffer (50 mM Tris HCl [pH 8], 150 mM NaCl, 1% NP–40, 0.5% sodium deoxycolate, and 0.1% SDS).Tumor and liver specimens are homogenized into RIPA buffer with an electric homogenizer and then maintained in constant agitationfor two hours at 4°C. The lysates are cleared by centrifugation. Each lysate (20 μg of protein) is separated by 8% SDS–PAGE andprobed with polyclonal rabbit antibodies against total ERK1/2, TβRI, and TβRII or with monoclonal mouse antibodies againstphosphorylated Smad2, total Smad2, phosphorylated ERK1/2, and phosphorylated and total JNK. Immunoreactive proteins arevisualized with Lumi–Light Western blotting substrate according to the manufacturer's instructions. phosphorylated Smad2/Smad2band density ratios are calculated using the ImageQuant software.Animal Administration: LY2109761 is dissolved in the SX–1292 oral vehicle (1% sodium carboxymethylcellulose, 0.5% sodiumlauryl sulfate, and 0.05% antifoam). [1]Fifty mice are randomLy allocated into five groups (n=5 mice per group) to receive p.o. vehiclefor 50 μL of LY2109761 or 50 mg/kg LY2109761 twice a day p.o. On day 0, mice are anesthetized with 1.5% isofluorane–air mixture, asmall left abdominal flank incision is created, and the spleen is carefully exteriorized. L3.6pl/GLT or C5LM2/GLT cells (1.0×105 cells/50μL of HBSS), cultured in the presence of LY2109761 (5 μM) or DMSO from day ?5 to day 0, are inoculated into the spleen with aProduct Name:LY2109761Cat. No.:HY-12075CAS No.:700874-71-1Molecular Formula:C26H27N5O2Molecular Weight:441.52Target:Autophagy; TGF–β ReceptorPathway:Autophagy; TGF–beta/SmadSolubility:10 mM in DMSO

GW4869_DataSheet_MedChemExpress

GW4869_DataSheet_MedChemExpress

Inhibitors, Agonists, Screening Data Sheet

BIOLOGICAL ACTIVITY: GW4869 is a noncompetitive neutral sphingomyelinase inhibitor with an IC50 of 1 μM.IC50 & Target: IC50: 1 μM (neutral sphingomyelinase)[1]In Vitro: GW4869 (10 μM) partially inhibits TNF–induced sphingomyelin (SM) hydrolysis, and 20 μM of the compound is protectedcompletely from the loss of SM. The addition of 10–20 μM GW4869 completely inhibits the initial accumulation of ceramide,whereas this effect is partially lost at later time points (24 h). The action of GW4869 occurs downstream of the drop in glutathione.GW4869 is able, in a dose–dependent manner, to significantly protect from cell death. These protective effects are accompanied bysignificant inhibition of cytochrome c release from mitochondria and caspase 9 activation, therefore localizing N–SMase activationupstream of mitochondrial dysfunction[1]. In Vivo: Pre–treatment with GW4869 significantly impairs release of both exosomes and pro–inflammatory cytokines (TNF–α, IL–1β,IL–6) in RAW264.7 macrophages. At 12 h after LPS treatment or CLP surgery, WT mice pretreated with GW4869 displays loweramounts of exosomes and pro–inflammatory cytokines in the serum than control PBS–injected mice. Accordingly, GW4869treatment diminishes the sepsis–induced cardiac inflammation, attenuates myocardial depression and prolongs survival[2]. PROTOCOL (Extracted from published papers and Only for reference) Kinase Assay:[1]B. cereu sphosphatidylcholine–PLC is incubated in the presence or absence of 10 μM GW4869 in a reaction mixturecontaining 100 mM Tris, pH 7.2, 25% glycerol, 20 mM p–nitrophenyl/phosphorylcholine, and production of p–nitrophenol isquantified spectrophotometrically at 410 nm. Protein phosphatase 2A from bovine kidney is incubated in the presence or absence ofGW4869 in buffer containing 50 mM Tris, pH 7.4, 1 mM dithiothreitol, 100 μM MnCl2, and 20% glycerol, and phosphatase activity ismeasured[1].Cell Assay: GW4869 is routinely stored at -80 °C as a 1.5 mM stock suspension in Me2SO. Right before use, the suspension issolubilized by the addition of 5% methane sulfonic acid (MSA) (2.5 μl of 5% MSA in sterile double–distilled H2O are added to 50μL of GW4869 stock suspension).[1]Cells are treated with GW4869 for 30 min and then TNF is added in 10 μL/well. At the indicatedtime points, 25 μL of MTT stock solution are added to each well and incubated at 37 °C in 5% CO2 for 3 h. The cell viability is usingthe MTT assay[1].Animal Administration: GW4869 is dissolved in DMSO (0.005%).[2]Mouse: The mice are randomly assigned to four groups: PBS,GW4869, PBS+LPS and GW4869+LPS (n=5 per group). GW4869 is intraperitoneally (i.p.) injected at one dose of 2.5μg/g. Mice inthe PBS+LPS group are pre–injected i.p. with PBS 1 h prior to an i.p. injection of LPS (25 μg/g). Mice in the group of GW4869+LPSare pre–injected i.p. with GW4869 (2.5μg/g) for 1 h, followed by an i.p. injection of LPS (25 μg/g, 100μl). Mice receive injections ofPBS to a comparable volume (100μl) as controls. The survival rate of the PBS+LPS and GW4869+LPS groups are monitored every 6h for a 36 h period[2].Product Name:GW4869Cat. No.:HY-19363CAS No.:6823-69-4Molecular Formula:C30H30Cl2N6O2Molecular Weight:577.50Target:OthersPathway:OthersSolubility:DMSO: 0.044 mg/mL (Need ultrasonic and warming)