NMDA_6384-92-5_DataSheet_MedChemExpress

Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:Tonabersat is a gap–junction modulator.IC50 & Target: Gap–junction [1]In Vitro: Tonabersat, a novel benzopyran derivative, inhibits cortical spreading depression (CSD) and therefore might be able to inhibit the early migraine mechanisms [1].In Vivo: Treatment with either Tonabersat (10 mg/kg) or Meclofenamate (20 mg/kg) as single agents significantly inhibitprogression of metastatic lesions. Addition of carboplatin to either agent profoundly inhibits brain metastasis [2].PROTOCOL (Extracted from published papers and Only for reference)Animal Administration: Tonabersat (purphased from MedChem Express) is prepared in 10% DMSO in polyethylene glycol400 (Mice)[2].[2]Mice [2]Athymic NCR nu/nu mice, Cr:NIH bg–nu–xid mice, B6129SF1/J, C57BL/6J–Tmem173gt /J ‘golden ticket’, and C57/Bl/6J mice are used at 5–6 weeks of age. For inducible knockdown experiments, mice are given doxycycline hyclate in the drinking water (2 mg/mL) and the diet 14 days after injection of cancer cells. For drug treatment experiments, mice are intraperitoneally injected with Carboplatin (5mg/kg per 5 days), Tonabersat (MedChem Express) (10 mg/kg per day), or meclofenamic acid sodium salt (20 mg/kg per day). Vehicle (10% DMSO in polyethylene glycol 400) is used in control mice. Quantification of tumour burden is by Bio–luminescent imaging (BLI),performed using an IVIS Spectrum Xenogen instrument and analysed using Living Image software v.2.50.References:[1]. Silberstein SD, et al. Tonabersat, a gap–junction modulator: efficacy and safety in two randomized, placebo–controlled, dose–ranging studies of acute migraine. Cephalalgia. 2009 Nov;29 Suppl 2:17–27.[2]. Chen Q, et al. Carcinoma–astrocyte gap junctions promote brain metastasis by cGAMP transfer. Nature. 2016 May 18;533(7604):493–8.Product Name:Tonabersat Cat. No.:HY-15204CAS No.:175013-84-0Molecular Formula:C 20H 19ClFNO 4Molecular Weight:391.82Target:Gap Junction Protein Pathway:Cytoskeleton Solubility:10 mM in DMSOCaution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@ Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。

Product Name:N6022CAS No.:1208315-24-5Cat. No.:HY-14984Product Data SheetMWt:414.46Formula:C24H22N4O3Purity :>98%Solubility:DMSOMechanisms:Biological Activity:N6022is a potent,selective,reversible,and efficacious S-Nitrosoglutathione reductase(GSNOR) Pathways:Others; Target:GSNOR N6022 is a potent, selective, reversible, and efficacious S Nitrosoglutathione reductase(GSNOR)inhibitor(IC50=10 nM) which is currently undergoing clinical development.IC50 value: 10 nM [1]Target: GSNOR in vitro: N6022 is a tight-binding, specific, and fully reversible inhibitor of GSNOR with an IC(50) of 8nM and a K(i) of 2.5 nM. We accounted for the fact that the NAD(+)- and NADH-dependent oxidation and reduction reactions, catalyzed by GSNOR are bisubstrate in nature in our calculations. N6022binds in the GSNO substrate binding pocket like a competitive inhibitor, although in kinetic assays it behaves with a mixed uncompetitive mode of inhibition (MOI) toward the GSNO substrate and a References:[1]. Sun X, et al. Structure-activity relationships of pyrrole based S-nitrosoglutathione reductase inhibitors: pyrrole regioisomers and propionic acid replacement. Bioorg Med Chem Lett. 2011 Jun15;21(12):3671-5 mixed competitive MOI toward the formaldehyde adduct, S-hydroxymethylglutathione (HMGSH) [3].in vivo:Sprague-Dawley rats were given 2, 10 or 50 mg/kg/day N6022 via IV administra...15;21(12):36715.[2]. Colagiovanni DB, et al. A nonclinical safety and pharmacokinetic evaluation of N6022: a first-in-class S-nitrosoglutathione reductase inhibitor for the treatment of asthma. Regul Toxicol Pharmacol.2012 Feb;62(1):115-24.[3]. Green LS, et al. Mechanism of inhibition for N6022, a first-in-class drug targeting S-nitrosoglutathione reductase. Biochemistry. 2012 Mar 13;51(10):2157-68.Caution: Not fully tested. For research purposes onlyMedchemexpress LLC18W i l k i n s o n W a y , P r i n c e t o n , N J 08540,U S AE m a i l : i n f o @m e d c h e m e x p r e s s .c o m W e b : w w w .m e d c h e m e x p r e s s .c o m。

JNJ-180386835 mg10 mgadministration. Concomitantly, the REM sleep latency tends to be prolonged in a dose-related manner with asignificant increase in REM latency occurring only at the highest dose tested (10 mg/kg; P<0.05). These alterations inREM sleep seem to be state-specific. A separate study is conducted to determine whether repeated administration ofJNJ-18038683 for 7 days would result in an adaptation of the EEG sleep response in particular on REM sleep in ratsduring the course of the treatment and after its discontinuation. JNJ-18038683 is administered for 7 consecutive days(1 mg/kg s.c. per day) at 2 h into the light phase. On the first day of treatment, JNJ-18038683 produces a significantdecrease in the time spent in REM sleep during the first 8 h after the injection and a prolongation of the REM sleeplatency. The REM sleep latency is increased during the 7-day repeated treatment and is normalized on the firstrecovery day after cessation of treatment. The significant decrease in REM sleep time is maintained during the 7-dayrepeated treatment, with a rebound occurring on the first recovery day after treatment discontinuation. The NREMsleep latency and the total NREM sleep time are not affected during the entire treatment[1].Cell Assay [1]HEK-293 cells stably expressing the rat 5-HT7 receptor are preincubated for 10 min with seven concentrations of JNJ-18038683 (10 μM-100 pM) followed by incubation with 100 nM of the agonist (5-HT). cAMP measurements aredetermined. SB-2699970 is used as the reference compound7receptor[1].MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Administration [1]Mice[1]Rat telemetry experiments are performed. In brief, telemetric devices are implanted in the peritoneal cavity of rats. After a 7-day recovery period, body temperature is measured noninvasively by radiotelemetry. On the day of the experiment, the baseline is monitored for 60 min before drug injection. Rat core temperature is continuously recorded, before and after injection, and averaged over each 2-min collection period. JNJ-18038683 (0.09, 0.9, and 9.0 mg/kg) is administered orally 6 h before 5-CT (0.1 mg/kg, i.p.) administration or intraperitoneally (0.027, 0.09, 0.18, 0.27, and 0.9 mg/kg) 20 min before 5-CT (0.1 mg/kg i.p.) administration (n=5 in each group). Change in core body temperature is calculated for all animals by comparing baseline before dosing to the minimal temperature reached after drug administration[1].MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES[1]. Bonaventure P, et al. Translational evaluation of JNJ-18038683, a 5-hydroxytryptamine type 7 receptor antagonist, on rapid eye movement sleep and in major depressive disorder. J Pharmacol Exp Ther. 2012 Aug;342(2):429-40.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。

PHA-680632TGI without signs of toxicity in the HL60 human acute myelogenous leukemia xenograft model. PHA-680632treatment at 60 mg/kg i.v. b.i.d. for 5 days results in 78% of TGI without signs of toxicity in the A2780 human ovariancarcinoma model[1]. PHA680632 in association with radiation leads to an additive effect in cancer cells, especially inthe p53-deficient cells, but does not act as a radiosensitiser[2].PROTOCOLKinase Assay [1]Inhibition of kinase activity by PHA-680632 is assessed using a scintillation proximity assay format. In this assay, the biotinylated substrate is transphosphorylated by the kinase in presence of ATP traced with γ33-ATP. Thephosphorylated substrate is then captured using streptavidin-coated scintillation proximity assay beads and theextent of phosphorylation is evaluated by β-counter after a 4-hour rest for the floatation of the beads on a dense 5 MCsCl solution. In particular a peptide derived from the Chocktide sequence (LRRWSLGL) is used as substrate forAurora A, whereas the optimized peptide Auroratide1 is employed for Aurora B and C. The assay is run in a robotizedformat on 96-well plates. The potency of the compound toward Aurora kinases and 29 additional kinases belongingto our Kinase Selectivity Screening panel is evaluated and the relevant IC50s are determined[1].MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay [1]Cells are seeded at different densities ranging from 5,000 to 15,000 cm2 in 24-well plate with the appropriate complete medium. After 24 hours, plates are treated with PHA-680632 and incubated for 72 hours at 37°C in 5% CO2atmosphere. At the end of incubation time, cells are detached from each plate and counted using a cell counter. IC50sare calculated using percentage of growth versus untreated control[1].MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Administration [2]Mice: Tumour xenograft mice are randomly allocated into four groups (six mice per group): A, control; B, IR alone, 8 Gy in 1 day; C, PHA-680632 alone, 40 mg/kg, b.i.d., for 4 days; D, same dose of PHA-680632 combined with IR (24 h after the first administration of PHA680632, similar schedule as IR alone) for 4 days. Drug or vehicle control (same volume of 20% Tween-80 in 5% glucose solution) is administered intraperitoneally (i.p.). The tumour size is measured twice a week using an electronic caliper. Follow-up of individual mice is conducted. The tumour volume is estimated from 2D tumour measurements[2].MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES[1]. Soncini C, et al. PHA-680632, a novel Aurora kinase inhibitor with potent antitumoral activity. Clin Cancer Res. 2006 Jul 1;12(13):4080-9.[2]. Tao Y, et al. Enhancement of radiation response by inhibition of Aurora-A kinase using siRNA or a selective Aurora kinase inhibitor PHA680632 in p53-deficient cancer cells. Br J Cancer. 2007 Dec 17;97(12):1664-72.Caution: Product has not been fully validated for medical applications. For research use only. Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@ Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。