Y06036 - Epigenetic Reader Domain 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEY06036Cat. No.: HY-111502CAS No.: 1832671-96-1分式: CHBrNOS分量: 427.27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 : 130 mg/mL (304.26 mM; Need ul

2、trasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.3404 mL 11.7022 mL 23.4044 mL5 mM 0.4681 mL 2.3404 mL 4.6809 mL10 mM 0.2340 mL 1.1702 mL 2.3404 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，

3、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: 2.17 mg/mL (5.08 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.17 mg/mL (5.08 mM); Clear solutionBIOLOGICAL ACTIVITY1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE物活性 Y06036種有效

4、的選擇性 BET 抑制劑，可與 BRD4(1) 溴結(jié)構(gòu)域結(jié)合，Kd 值為 82 nM 1。具有抗腫瘤活性1。IC50 & Target BRD4(1)82 nM (Kd)體外研究 Y06036 (0.001-100 nM, 96 hours for LNCaP, C4-2B, and 22Rv1 cells; 144 hours for VCaP cells) exhibits lowmicromolar or nanomolar potencies (IC50: 0.29-2.6 ) in the four androgen receptor (AR)-positive prostateca

5、ncer cell lines LNCaP, C4-2B, 22Rv1, and VCaP. Treatment of 22Rv1 cells with Y06036 (1, 2, 4, 8, and 16M, 48 hours) results in significant down-regulation of both full-length (AR-fl) and AR variants levels 1.Cell Viability Assay 1Cell Line: LNCaP, C4-2B, 22Rv1, and VCaP prostate cancer cellsConcentr

6、ation: 0.001-100 MIncubation Time: 96 hours for LNCaP, C4-2B, and 22Rv1; 144 hours for VCaPResult: Inhibited LNCaP, C4-2B, 22Rv1, and VCaP cells with IC50s of 1.06, 2.62, 1.50, 0.63 M,respectively.Western Blot Analysis 1Cell Line: 22Rv1 cellsConcentration: 1,2,4,8, and 16 MIncubation Time: 48 hoursR

7、esult: Resulted in significant down-regulation of both AR-fl and AR variants levels體內(nèi)研究 Y06036 (50 mg/kg, i.p. injection, 5 times per week, 25 days) demonstrates therapeutic effects in a C4-2BCRPC xenograft tumor model in mice. Y06036 is well tolerated in the treated mice, based on the weight ofthe

8、animal body and their general behavior 1.Animal Model: Four-week-old male mice (strain: C.B-17/IcrHsd-Prkdcscid for C4-2B) with C4-2B mousexenograft model 1Dosage: 50 mg/kg, 100 LAdministration: Intraperitoneal (i.p.) injection, 5 times per week, 25 daysResult: Exhibited strong antitumor activities

9、during the 25-day treatment period, with a tumorgrowth inhibition (TGI) of 70%.REFERENCES2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE1. Zhang M, et al. Structure-Based Discovery and Optimization of Benzo disoxazole Derivatives as Potent and Selective BET Inhibitorsfor Potential Treatment of Castration-Resistant Prostate Cancer (CRPC). J Med Chem. 2018 Apr 12;61(7):3037-3058.McePdfHeightCaution: Product has not been fully validated for m