CC-115_hydrochloride_DataSheet_MedChemExpress

Inhibitors, Agonists, Screening Data Sheet

BIOLOGICAL ACTIVITY: AR–C155858 is a novel inhibitor of the monocarboxylate transporters (MCTs) MCT1 and MCT2 (Ki values are 2.3 and < 10 nM,respectively), and exhibits no activity at MCT4.IC50 & Target: Ki: 2.3 nM (MCT1), 10 nM (MCT2)In Vitro: AR–C155858 (10 nM–100 nM) inhibits MCT1/MCT2 C–terminal chimaeras[1]. AR–C155858 inhibits MCT2, and the 70%inhibition seen at 10 nM is followed by a gradually increasing inhibition which can only be explained by a Ki value of significantlyless than 10 nM. AR–C155858 inhibits MCT1 expressed in Xenopus oocytes in a time– and concentration–dependent manner[2].PROTOCOL (Extracted from published papers and Only for reference) Kinase Assay:[1]MCT kinetic assays are performed by monitoring intracellular pH with H+–sensitive dye BCECF or bydetermining the uptake of l–[14C]lactate (7.4 MBq/mL). The uptake buffer containes 75 mM NaCl, 2 mM KCl, 0.82 mM MgCl2,1 mM CaCl2 and 20 mM Tris/Hepes (pH 7.4). AR–C155858 inhibitor titrations are performed at pH 6 with oocytes preincubated for45 min in a different uptake buffer (75 mM NaCl, 2 mM KCl, 0.82 mM MgCl2, 1 mM CaCl2 and 20 mM Mes, pH 6) containingthe required concentration of AR–C155858 prior to measuring the uptake of l–[14C]lactate (0.5 mM). Unless stated otherwise, uptake isdetermined over 2.5 min for all MCT constructs except for MCT2trn with or without embigin and MCT2/1 with or without embigin,where 5 and 10 min are used respectively.Cell Assay: AR–C155858 is dissolved in DMSO.[1]The erythrocytes (5% haematocrit) are pre–incubated for 1 h at roomtemperature (22°C) with or without AR–C155858 at the required concentration before assaying transport of l–lactate (10 mM) at6°C. Initial rates of transport are calculated by first–order regression analysis of the time course of pH change and convertedinto nmol of H+/min by determining the pH change induced by small additions of standardized NaOH.References: [1]. Ovens MJ, et al. The inhibition of monocarboxylate transporter 2 (MCT2) by AR–C155858 is modulated by the associated ancillary protein. Biochem J.2010 Oct 15;431(2):217–25.[2]. Ovens MJ, et al. AR–C155858 is a potent inhibitor of monocarboxylate transporters MCT1 and MCT2 that binds to an intracellular site involvingtransmembrane helices 7–10. Biochem J. 2010 Jan 15;425(3):523–30.Product Name:AR–C155858Cat. No.:HY-13248CAS No.:496791-37-8Molecular Formula:C21H27N5O5SMolecular Weight:461.53Target:Monocarboxylate TransporterPathway:Membrane Transporter/Ion ChannelSolubility:10 mM in DMSO

Inhibitors, Agonists, Screening Data Sheet

BIOLOGICAL ACTIVITY: KDM5–IN–1 is a potent, selective and orally bioavailable KDM5 inhibitor with an IC50 of 15.1 nM.IC50 & Target: IC50: 15.1 nM (KDM5); EC50: 0.34 μM (PC9 H3K4Me3)[1]In Vitro: KDM5–IN–1 is found to potently inhibit KDM5B and KDM5C isoforms (IC50 of 4.7 and 65.5 nM, respectively). It issignificantly less potent against other KDM enzymes (1A, 2B, 3B, 4C, 5A, 6A, 7B), inhibiting KDM4C the strongest with an IC50 of 1.9μM. KDM5–IN–1 still displays more than 100–fold selectivity for KDM4C vs. KDM5A[1].In Vivo: When dosed orally in mice at 50 mg/kg twice a day, KDM5–IN–1 shows an unbound maximal plasmaconcentration Cmax>15–fold over its cell EC50, thereby providing a robust chemical probe for studying KDM5 biological functions invivo[1].References: [1]. Liang J, et al. Lead optimization of a pyrazolo[1,5–a]pyrimidin–7(4H)–one scaffold to identify potent, selective and orally bioavailable KDM5 inhibitorssuitable for in vivo biological studies. Bioorg Med Chem Lett. 2016 Aug 15;26(16):4036–41.Product Name:KDM5–IN–1Cat. No.:HY-100422CAS No.:1628210-26-3Molecular Formula:C17H20N6OMolecular Weight:324.38Target:OthersPathway:OthersSolubility:DMSO: ≥ 30 mg/mL

Product Name:PDE1-IN-1CAS No.: 1160521-50-5Cat. No.:HY-12501MWt:507.56Formula:C29H26FN7OPurity :>98%

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Caution: Not fully tested. For research purposes onlyMedchemexpress PDE1-IN-1 is a potent PDE1 inhibitor; neuroprotective agent. IC50 value: Target: PDE1 inhibitor Methods for treatment of central nervous system disease (CNS) diseases, disorders, and/or injuries using inhibitors of phosphodiesterase-1 (PDE1) By Wennogle, Lawrence. From PCT Int. Appl. (2014), WO 2014145617 A2 20140918. Salt crystals of (6aR,9aS)-5,6a,7,8,9,9a-hexahydro-5-methyl-3-(phenylamino)-2-((4-(6-fluoropyridin-2- yl)phenyl)methyl)cyclopent[4,5]imidazo[1,2-a]pyrazolo[4,3-e]pyrimidin-4(2H)-oneBy Li, Peng; Wennogle, Lawrence P.; Davis, Robert; Buckton, Graham; Hooper, Mark, From PCT Int. Appl. (2013), WO 2013192556 A2 20131227. Organic compounds as phosphodiesterase 1 inhibitor compounds for the treatment of mental disorders By Fienberg, Allen A.; Wennogle, Lawrence J.; Mates, Sharon From PCT Int. Appl. (2010), WO 2010132127 A1 20101118.Preparation of ... Pathways:Others; Target:PDEProduct Data Sheet

Product Name:Bedaquiline fumarate

CAS No.: 845533-86-0

Cat. No.:HY-14881AProduct Data Sheet

MWt:671.58

Formula:C36H35BrN2O6

Purity :>98%

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DMSO

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Bedaquiline fumarate(TMC207; R207910) is an anti-tuberculosis drug which selectively inhibit the

Pathways:Anti-infection; Target:Antibacterial

q(;)gy

mycobacterial energy metabolism i.e. ATP synthesis and found to be effective against all states of Mycobacterium tuberculosis.

IC50 value:

Target: anti-TB

Preclinical studies have shown the efficacy of bedaquiline in terms of reduction in bacterial load and

treatment duration. Phase II clinical studies have established the safety, tolerability and earlier

sputum conversion time in patients with MDR-TB. In 2012 FDA approved bedaquiline for treatment

of MDR-TB and XDR-TB [1]. Bedaquiline possesses a unique mechanism of action that disrupts the