1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEBAY1238097Cat. No.: HY-112316CAS No.: 1564268-08-1分式: CHNO分量: 451.56作靶點(diǎn): Epigenetic Reader Domain作通路: Epigenetics儲(chǔ)存式: 4C, stored under nitrogen* In solvent : -80C, 6 months; -20C, 1 month (stored undernitrogen)溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 1

2、50 mg/mL (332.18 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.2145 mL 11.0727 mL 22.1455 mL5 mM 0.4429 mL 2.2145 mL 4.4291 mL10 mM 0.2215 mL 1.1073 mL 2.2145 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。體內(nèi)實(shí)驗(yàn) 請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?，配制前?qǐng)先配制澄清的儲(chǔ)備液，再依次添加助溶劑(為保證實(shí)驗(yàn)結(jié)果的可靠性，體內(nèi)實(shí)驗(yàn)的作

3、液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.54 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.54 mM); Clear solution3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubi

4、lity: 2.5 mg/mL (5.54 mM); Clear solution1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 BAY1238097種有效的、BET 與組蛋 結(jié)合的選擇性抑制劑，通過(guò)下調(diào)c-Myc平及下游轉(zhuǎn)錄組，在AML(急性髓性病) 和MM (多發(fā)性髓瘤) 模型中表現(xiàn)出較強(qiáng)的抗增殖活性 (IC50 值 100 nM)。IC50 & Target IC50: 100 nM (BET in a TR-FRET assay) 1.體外研究 BAY 1238097 shows stron

5、g inhibitory activity (IC50 100 nM) in a TR-FRET assay using BET BRD4bromodomain 1 and an acetylated peptide derived from histone H4. In the NanoBRET assay, the interactionbetween BRD4 (IC50=63 nM), BRD3 or BRD2 (IC50=609 nM) and H4 (IC50=2430 nM) is inhibited 1.BAY 1238097 has in vitro anti-tumour

6、activity in lymphoma models. BAY 1238097 affects the geneexpression of GCB DLBCL cells. At the gene level, BTK, CCDC86, CCND2, CD19, CD27, FAIM, FCMR(FAIM3), IL7R, IRAK1, MAPK13, MYB, MYC, PDE4B, TNFRSF13B, TNFRSF17 are among the topdownregulated genes. Beside histone-coding genes, the upregulated g

7、enes include CCL5, CDKN2C, CD69,JUN, and MKNK2 2.體內(nèi)研究 BAY 1238097 shows strong efficacy in the AML and MM models. BAY 1238097 has in vivo anti-tumouractivity in lymphoma models 1 2.BAY 1238097 is well tolerated at 10-15 mg/kg applied daily over 9-14 days in different disease models, withno obvious t

8、oxicity 1 2.Animal Model: Severe combined immunodeficiency (SCID) female mice (9-12 weeks old) inoculatedsubcutaneously into the right flank with 5106 SU-DHL-8 cells/mouse suspended in 0.1mL of matrigel or with ODosage: 15 mg/kg (maximal tolerated dose).Administration: Orally daily for 12 days (on d

9、ay 21 post-tumour inoculation).Result: Showed strong efficacy in the AML models THP-1, MOLM-13 and KG-1, with T/Cbetween 13 and 20%. Also active in MM models in a human IGH-cyclin D1 translocatedMOLP-8 model with a T/C of 3% 2.REFERENCES1. Lejeune, P., et al. (2015) Abstract 3524: BAY 1238097, a nov

10、el BET inhibitor with strong efficacy in hematological tumor models. CancerResearch, 75(15 Suppl), 884.2. Bernasconi E, et al. Preclinical evaluation of the BET bromodomain inhibitor BAY 1238097 for the treatment of lymphoma. Br JHaematol. 2017 Sep;178(6):936-948.McePdfHeightCaution: Product has not been fully valida