NI-57 - Epigenetic Reader Domain 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemENI-57Cat. No.: HY-19537CAS No.: 1883548-89-7分式: CHNOS分量: 383.42作靶點(diǎn): Epigenetic Reader Domain作通路: Epigenetics儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 83.3 mg/mL (217.26 mM)* means sol

2、uble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.6081 mL 13.0405 mL 26.0811 mL5 mM 0.5216 mL 2.6081 mL 5.2162 mL10 mM 0.2608 mL 1.3041 mL 2.6081 mL請(qǐng)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(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 NI-57 為溴結(jié)構(gòu)域和植物同鋅指結(jié)構(gòu)域 (BRPF) 蛋家族的抑制劑，對(duì) BRPF1，BRPF2 (BR

3、D1) 和 BRPF3 的IC50 值分別為 3.1，46 和 140 nM。IC50 & Target IC50: 3.1 nM (BRPF1), 46 nM (BRPF2 (BRD1), 140 nM (BRPF3) 1體外研究NI-57 is an inhibitor of bromodomain and plant homeodomain finger-containing (BRPF), with IC50s of 3.1, 461/2 Master of Small Molecules 您邊的抑制劑師www.MedChemEand 140 nM for BRPF1, BRPF2 (

4、BRD1) and BRPF3, respectively. NI-57 binds the BRD of BRPF1 with a Kdof 31 2 nM, BRD1 with a Kd of 110 13 nM, and BRPF3 with a Kd of 410 47 nM, whereas binding toBRD9 is weaker (Kd 1000 130 nM) measured by isothermal titration calorimetry. NI-57 shows less activeeffect on BRD9 (IC50, 520 nM) and BRD

5、4 (BD1) (IC50, 3700 nM), TRIM24 (IC50, 1600 nM). NI-57 alsoinhibits BRPF BRDs in the nucleus, but shows little effect on the proliferation of many cancer cell lines withGI50s of 10.4 M (NCI-H1703 cells), 14.7 M (DMS114), 15.6 M (HRA-19), and 16.6 M (RERF-LC-Sq1).Furthermore, Inhibition on BRPF1 of N

6、I-57 (10 M) reduces the gene expression of CCL-22 by 27.7 9.4%1.體內(nèi)研究 NI-57 has favorable oral bioavailability in mice 1.PROTOCOLKinase Assay 1 All reagents are diluted in the recommended buffer (50 mMHEPES, 100 mM NaCl, 0.1% BSA; pH = 7.4)supplemented with 0.05% CHAPS and allowed to equilibrate to r

7、oom temperature prior to addition to plates.4 mL of HIS-tagged protein is added to low-volume 384-well plates, followed by 4 mL of either buffer, non-biotinylated peptide, solvent or compounds (NI-57, etc.). Plates are sealed and incubated at roomtemperature for 30 minutes, before the addition of 4

8、mL biotinylated peptide, resealing and incubation for afurther 30 minutes. 4 mL of streptavidin-coated donor beads (25 g/mL) and 4 L of nickel chelate acceptorbeads (25 g/mL) are then added under low light conditions. Plates are foil sealed to protect from light,incubated at room temperature for 60

9、minutes and read on a PHERAstar FS plate reader using anAlphaScreenTM 680 excitation/570 emission filter set. IC50s are calculated in GraphPad Prism 5. Results forcompounds (NI-57, etc.) dissolved in DMSO are normalised against corresponding DMSO controls prior toIC50 determination, which are given

10、as the final concentration of compound in the 20 L reaction volume 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Igoe N, et al. Design of a Chemical Probe for the Bromodomain and Plant Homeodomain Finger-Containing (BRPF) Family of Proteins.J Med Chem. 2017 Aug 24;60(16):6998-7011.McePdfHeightCaution: Product has not been fully va