PP121_DataSheet_MedChemExpress

Inhibitors, Agonists, Screening Data Sheet

BIOLOGICAL ACTIVITY: Miridesap is a ligand for serum amyloid P component (SAP) and intends to inhibit and dissociate SAP binding to amyloid fibrils andtangles.IC50 & Target: SAP[1]In Vitro: Miridesap is a ligand for serum amyloid P component (SAP) and intends to inhibit and dissociate SAP binding to amyloidfibrils and tangles[1]. Miridesap depletes circulating SAP almost completely but leaves some SAP in amyloid deposits for specificrecognition by subsequently administered therapeutic anti-SAP antibodies[2].References: [1]. Kolstoe SE, et al. Molecular dissection of Alzheimer's disease neuropathology by depletion of serum amyloid P component. Proc Natl Acad Sci U S A.2009 May 5;106(18):7619-23.[2]. Sahota T,et al. Target Mediated Drug Disposition Model of CPHPC in Patients with Systemic Amyloidosis. CPT Pharmacometrics Syst Pharmacol. 2015Feb;4(2):e15.Product Name:MiridesapCat. No.:HY-101861CAS No.:224624-80-0Molecular Formula:C16H24N2O6Molecular Weight:340.37Target:OthersPathway:OthersSolubility:DMSO: 300 mg/mL

SemaglutideCat. No.:HY-114118CAS No.:910463-68-2Target:Glucagon ReceptorPathway:GPCR/G ProteinStorage:Please store the product under the recommended conditions in the COA.

Solvent & SolubilityIn Vitro10 mM in DMSOBIOLOGICAL ACTIVITYDescriptionSemaglutide, a long-acting GLP-1 analogue, is a glucagon-like peptide-1 (GLP-1) receptor agonist that can be used in the treatment of type 2 diabetes.IC₅₀ & TargetGLP-1 receptor[1].In VitroSemaglutide has two amino acid substitutions compared to human GLP-1 (Aib8, Arg34) and is derivatized at lysine 26. The GLP-1R affinity of Semaglutide is 0.38±0.06 nM[1]. Semaglutide is a GLP-1 analogue with 94% sequence omology to human GLP-1[3.In VivoThe plasma half-life of Semaglutide is 46h in mini-pigs following i.v. administration and semaglutide has an MRT of 63.6h after s.c. dosing to mini-pigs[1]. Semaglutide improves 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)-induced motor impairments. In addition, Semaglutide rescues the decrease of tyrosine hydroxylase (TH) levels, alleviates the inflammation response, reduces lipid peroxidation, inhibits the apoptosis pathway, and also increases autophagy- related protein expression, to protect dopaminergic neurons in the substantia nigra and striatum. Moreover, the long-acting GLP-1 analogue semaglutide is superior to liraglutide in most parameters[2]. Semaglutide lowers blood glucose by stimulating the release of insulin and also lowers body weight[3].PROTOCOLMice[2] Male C57BL/6 mice 10 weeks old (20-25 g) are used throughout the study. Mice are randomized divided into six groups (n=12 per group) (i) control group treated with saline alone; (ii) liraglutide group treated with saline and liraglutide (25 nmol/kg ip. once daily for 7 days); (iii) Semaglutide group treated with saline and Semaglutide (25 nmol/kg ip. once daily for 7 days), (iv) MPTP group treated with MPTP alone (once daily 20 mg/kg ip. for 7 days); (v) Animal Administration [2]Product Data SheetInhibitors•Agonists•Screening Libraries

File D:\CHEM32\1\DATA\CPK\CPK2016-N16-11422.D Tgt Mass (EZX): 331.00 Injection Date : 17 Nov 16 5:48 pm +0800 Seq. Line : 0 Sample Name : CPK2016-N16-11422 Location : P1-B-01 Acq. Operator : KFF(LCMS-02) Inj : 1

Spec. Reported : MS Integration Inj Volume : 1 ul Acq. Method : D:\Chem32\1\METHODS\1-POS-3MIN.M Analysis Method : D:\CHEM32\1\METHODS\1-POS-3MIN-PROSRSS.M Catalog No : HY-13942 Batch#11422 Easy-Access Method: '1-POS-3MIN' 331.00 Method Info : Mobile Phase: A: water(0.01%TFA) B:ACN(0.01%TFA) Gradient: 5% to 95%B within 1.3 min Flow Rate :1.8ml/min Column :SunFire C18, 4.6*50mm,3.5um A-RP-186 Oven Temperature : 45C

min*0.511.522.5mAU

010002000*DAD1 B, Sig=214,4 Ref=off

1.4521.5291.660

1.9132.083

min*0.511.522.5mAU

0200400600*DAD1 C, Sig=254,4 Ref=off

1.660

1.9652.083

min0.511.522.50200000400000600000 MSD1 TIC, MS File ES-API, Pos, Scan, Frag: 70

Inhibitors, Agonists, Screening Data Sheet

BIOLOGICAL ACTIVITY: Mocetinostat is a potent isotype–selective HDAC inhibitor with IC50 of 0.15, 0.29, 1.66 and 0.59 μM for HDAC1, HDAC2, HDAC3 andHDAC11, respectively.IC50 & Target: IC50: 0.15 μM (HDAC1), 0.29 μM (HDAC2), 1.66 μM (HDAC3), 0.59 μM (HDAC11)[1]In Vitro: Mocetinostat (MGCD0103) exhibits potent and selective antiproliferative activities against a broad spectrum of humancancer cell lines in vitro, and HDAC inhibitory activity is required for these effects. In all cell lines tested, Mocetinostat (MGCD0103)partially inhibits cellular HDAC enzyme activity although the maximal inhibition of activity varies among cell lines from 75% to 85%of total activity. The IC50 of Mocetinostat in intact cancer cells is independent of tissue origin. In A549 cells, MGCD0103 showsdose–dependent inhibition of HDAC activity in whole cells. At high concentrations in A549 cells, Mocetinostat inhibits a maximum of80% of total activity. In HCT116 cells, Mocetinostat induces a significant S–phase depletion and both G1 and G2–M accumulation[1].In Vivo: Mocetinostat (MGCD0103) significantly inhibits growth of human tumor xenografts in nude mice in a dose–dependentmanner and the antitumor activity correlated with induction of histone acetylation in tumors. The p.o. administration ofMocetinostat (MGCD0103) (2HBr salt) significantly reduces growth of implanted advanced A549 tumors in nude mice in adose–dependent manner after 13 days of daily administration. Mocetinostat (170 mg/kg for 2HBr salt, corresponding to 120 mg/kgof free base) significantly blocks growth of tumors compared with vehicle treatment alone (P<0.05 in post–ANOVA Dunnett's test)with no change in body weight[1]. PROTOCOL (Extracted from published papers and Only for reference) Kinase Assay:[1]The deacetylase enzyme assay is based on a homogeneous fluorescence release assay. Purified recombinant HDACenzymes are incubated with Mocetinostat (MGCD0103) diluted in various concentrations for 10 min in assay buffer [25 mM HEPES(pH 8.0), 137 mM NaCl, 1 mM MgCl2, 2.7 mM KCl] at room temperature. The substrate Boc–Lys(ε–Ac)–AMC (Bachem) is added to thereaction for further incubation at 37°C. The concentration of the substrate and the incubation time varies for different isotypes ofHDAC enzymes. A 20–min trypsin incubation at room temperature allows the release of the fluorophore from the deacetylatedsubstrate. The fluorescent signal is detected by fluorometer at excitation of 360 nm, emission of 470 nm, and cutoff at 435 nm. TheIC50 values of the compounds are determined by analyzing dose–response inhibition curves[1].Cell Assay: Mocetinostat (MGCD0103) is dissolved in DMSO and stored, and then diluted with appropriate media before use[1].[1]Cells in 96–well plates are incubated with Mocetinostat at various concentrations for 72 h at 37°C in 5% CO2. MTT is added at afinal concentration of 0.5 mg/mL and incubated with the cells for 4 h before an equal volume of solubilization buffer [50% N,N–dimethylformamide, 20% SDS (pH 4.7)] is added. After overnight incubation, solubilized dye is quantified by reading at 570 nmusing a reference at 630 nm. Absorbance values are converted to cell numbers according to a standard growth curve of therelevant cell line. The concentration which reduces cell numbers to 50% relative to DMSO–treated cells is determined as MTT IC50[1].Animal Administration: Mocetinostat (MGCD0103) is dissolved in vehicle (PBS acidified with 0.1 N HCl or PEG400/0.2 N HCl saline,Product Name:MocetinostatCat. No.:HY-12164CAS No.:726169-73-9Molecular Formula:C23H20N6OMolecular Weight:396.44Target:HDAC; HDAC; AutophagyPathway:Epigenetics; Cell Cycle/DNA Damage; AutophagySolubility:10 mM in DMSO