C646-DataSheet-生命科學試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEC646Cat. No.: HY-13823CAS No.: 328968-36-1分式: CHNO分量: 445.42作靶點: Histone Acetyltransferase; Autophagy; Epigenetic ReaderDomain作通路: Epigenetics; Autophagy儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)

2、體外實驗 DMSO : 36 mg/mL (80.82 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.2451 mL 11.2254 mL 22.4507 mL5 mM 0.4490 mL 2.2451 mL 4.4901 mL10 mM 0.2245 mL 1.1225 mL 2.2451 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 C646選擇性，競爭性

3、的 histone acetyltransferase p300 抑制劑，Ki 值為 400 nM，對其他的酰轉(zhuǎn)移酶作較。IC50 & Target Ki: 400 nM (histone acetyltransferase p300)1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE體外研究 C646 is a linear competitive inhibitor of p300 versus acetyl-CoA with a Ki of 400 nM. C646 shows anoncompetitive pattern of p300

4、 inhibition versus H4-15 peptide substrate. C646 treatment reduces histoneH3 and H4 acetylation levels and abrogates TSA-induced acetylation in cells. C646 has a more potent effecton cell growth than Lys-CoA-Tat does 1. C646 enhances mitotic catastrophe after IR and suppressesphosphorylation of CHK1

5、 after IRin A549 cells 2. C646 attenuates the increased acetylation of GATA1 andthe increased transcriptional activity of GATA1 induced by EDAG 3.PROTOCOLKinase Assay 1 Reactions are carried out at 30C for times varying from 2 to 4 min under the following reaction conditions: 50mM HEPES, pH 7.9, 50

6、mM NaCl, 0.05 mg/mL BSA, 5 mM DTT, 0.05 mM EDTA, 0.25% DMSO, 10 M of X.laevis histone H3, and varying concentrations of C646 (0, 3, 10 M). The reactions contains either 70nanograms of Rtt109/Vps75, 15 nanograms of yGcn5, 300 nanograms of the SAS complex or 1 microgramof hMOZ. The amount of enzyme us

7、ed in each assay is estimated by comparing Coomassie Blue staining ofsamples with bovine serum albumin standards, analyzed by SDS. The mixture is allowed toequilibrate at 30C for 10 min before the reaction is initialed with addition of a 1:1 mixture of 12C-AcCoAand 14C-AcCoA to a final concentration

8、 of 20 M. After the appropriate time the reaction is quenched with 6X Tris-Tricine gel loading buffer which contains 0.2mol/LTris-Cl pH 6.8, 40% v/v glycerol, 14% w/v SDS, 0.3mol/LDTT, and 0.06% w/v Coomassie Blue. The 14C-labeled histone substrates are separated fromreactants on a 16.5% Tris-Tricin

9、e SDSgel. The rate of 14C-incorporation into histone H3 is quantifiedby autoradiography. All assays are in duplicate, and these generally agree within 20%.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 2 Cells are seeded in 6-well plates, in

10、cubated at 37C for 4-10 h for attachment, and exposed (or not) to C646.After incubation for 2 h, the cells are subjected (or not) to IR and incubated for 10 days for colony formation.The cells are fixed with methanol and stained with crystal violet. Colonies of at least 50 cells are counted.The surv

11、iving fraction is normalized to the corresponding controls. The dose required to reduce the survivingfraction to 10% (D10) of the irradiated cells is calculated by using the linear-quadratic model.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的

12、科研獻 Nucleic Acids Res. 2019 Mar 18;47(5):2455-2471. Cell Death Differ. 2018 Nov;25(11):1980-1995. Free Radic Biol Med. 2018 Aug 20;124:454-465. Hum Reprod. 2019 Jun 13. pii: dez068. Cell Cycle. 2019 Jun 25:1-14.See more customer validations on HYPERLINK / www.MedChemEREFERENCES2/3 Master of Small Mo

13、lecules 您邊的抑制劑師www.MedChemE1. Bowers EM, et al. Virtual ligand screening of the p300/CBP histone acetyltransferase: identification of a selective small moleculeinhibitor. Chem Biol. 2010 May 28;17(5):471-82.2. Oike T, et al. C646, a selective small molecule inhibitor of histone acetyltransferase p300, radiosensitizes lung cancer cells byenhancing mitotic catastrophe. Radiother Oncol. 2014 May;111(2):222-7.3. Zheng WW, et al. EDAG positively regulates erythroid differentiation and modifies GATA1 acetylation through recruiting p300. StemCells. 2014 Aug;32(8):2