Pracinostat-SB939-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEPracinostatCat. No.: HY-13322CAS No.: 929016-96-6Synonyms: SB939分式: CHNO分量: 358.48作靶點(diǎn): HDAC作通路: Cell Cycle/DNA Damage; Epigenetics儲存式: 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 : 50 mg/mL (1

2、39.48 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.7896 mL 13.9478 mL 27.8956 mL5 mM 0.5579 mL 2.7896 mL 5.5791 mL10 mM 0.2790 mL 1.3948 mL 2.7896 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。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)動物和給藥式選擇適當(dāng)?shù)娜芙獍?，配制前請先配制澄清的儲備液，再依次添加助溶?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

3、；澄清的儲備液可以根據(jù)儲存條件，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. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.75 mg/mL (7.67 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.75 mg/mL (7.67 mM); Clear solution3. 請依序添加每種溶劑： 10% DMSO 90% corn oil1/3 Master of Sm

4、all Molecules 您邊的抑制劑師www.MedChemESolubility: 2.75 mg/mL (7.67 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Pracinostat種有效的組蛋去?；?(HDAC) 抑制劑，對 HDACs 的 IC50 值為 40-140 nM，可于癌癥研究。IC50 & Target HDAC10 HDAC3 HDAC5 HDAC140 nM (IC50) 43 nM (IC50) 47 nM (IC50) 49 nM (IC50)HDAC4 HDAC9 HDAC11 HDAC256 nM (IC50) 70

5、 nM (IC50) 93 nM (IC50) 96 nM (IC50)HDAC7 HDAC8 HDAC6137 nM (IC50) 140 nM (IC50) 1008 nM (IC50)體外研究 Pracinostat (SB939) is a potent novel hydroxamate-based inhibitor of HDACs class I, II, and IV, inhibiting theisolated enzymes with a Ki of 19 to 48 nM (class I), 16 to 247 nM (class II), and 43 nM (c

6、lass IV), but with noactivity against the class III isoenzyme SIRT I. SB939 has effects on HCT-116 colon cancer cell line and theHL-60 acute myeloid leukemia cell line, with IC50s of 0.48 M and 70 nM, respectively. SB939 does notinhibit the proliferation of normal human dermal fibroblasts at concent

7、rations up to 100 M 1. Pracinostat(SB939, compound 3) inhibits CYP2C19 with IC50 of 5.78 M. SB939 shows potent activities against A2780,COLO 205, HCT-116, and PC-3 cell lines, with IC50s of 0.48 0.21, 0.56 0.08, 0.48 0.27, and 0.34 0.06 2. Pracinostat downregulates JAK and FLT3 signaling in JAK2V617

8、F and FLT-ITD cell lines, andshows synergy in combination with pacritinib. Pracinostat and pacritinib show in vitro synergy on STATsignaling and apoptosis. Pracinostat potently inhibits proliferation of different AML subtypes as a single agentand is synergistic with pacritinib in JAK2V617F or FLT3-I

9、TD AML cell lines 3.體內(nèi)研究 Pracinostat (SB939, 25-100 mg/kg) shows significant dose-dependent growth inhibition of HCT-116xenografts. SB939 selectively accumulates in tumor tissue. SB939 (50 or 75 mg/kg) exhibits anti-tumoractivities in the Apcmin genetic colon cancer mouse model 1. Pracinostat (25 or

10、 50mg/kg per day for 21days) induces significant inhibition of tumor growth (TGI), by 59 and 116%, respectively, in mice bearingMV4-11 xenografts. Pracinostat (75mg/kg, q.o.d) in combination with pacritinib is efficacious and synergisticin vivo in two different models of human AML. Pracinostat and p

11、acritinib have synergistic effects on AML-induced plasma cytokines/growth factors/chemokines 3.PROTOCOLCell Assay 1 Cells are seeded in 96-well plates at a predetermined optimal density, in the log growth phase, and rested for24 h (adherent cells) or 2 h (suspension cells), respectively, before trea

12、tment with SB939. All experimentsare done in triplicates for 96 h, with 1% solvent, using either the CyQUANT Cell proliferation assay kit foradherent cells or the CellTiter96 Aqueous One solution cell proliferation kit for suspension cells, in a totalvolume of 100 L with SB939 concentrations from 10

13、0 M to 1.5 nM in nine serial dilution steps. IC50 are2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEdetermined using the XLfit software 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Male ApcMin/+ mice and female C57BL/6 mice are fed a stand

14、ard rodent diet. Mice with the confirmedAdministration 1 mutation, between 16 and 20.5 wk of age, with a positive scoring in the hemocult assay are recruited to theexperiment. During treatment, mice are injected i.p. with 40 mg/kg of 5-FU in a volume of 200 L per 20 gbody weight, once daily, for 5 d

15、 of treatment, followed by a 9-d recovery period and an additional 5 d oftreatment. Treatment with SB939 per oral at 50 or 75 mg/kg once daily is given continuously for 21 d. At thelast day of the treatment, the small intestine, caecum, and colon are removed; fixed by multiple injections of4% PBS-bu

16、ffered formaldehyde into the gut lumen; cut into segments; and spread flat on a plastic film in aformaldehyde bath. Tumor load is measured in a dissection microscope. Assessment and analysis of thesamples are done blinded 1.MCE has not independently confirmed the accuracy of these methods. They are

17、for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Proc Natl Acad Sci U S A. 2019 Feb 19;116(8):2961-2966. J Mol Med (Berl). 2019 Jun 14. Drug Des Devel Ther. 2018 Apr 30;12:1009-1017. Harvard Medical School LINCS LIBRARYSee more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Novotny-Diermayr V, et al. SB

18、939, a novel potent and orally active histone deacetylase inhibitor with high tumor exposure and efficacy inmouse models of colorectal cancer. Mol Cancer Ther. 2010 Mar;9(3):642-52.2. Wang H, et al. Discovery of (2E)-3-2-butyl-1-2-(diethylamino)ethyl-1H-benzimidazol-5-yl-N-hydroxyacrylamide (SB939), an orallyactive histone deacetylase inhibitor with a superior preclinical profile. J Med Chem. 2011 Jul 14;54(13):4694-720.3. Novotny-Diermayr V, et al. The oral HDAC inhibitor pracinostat (SB939) is efficacious and synergistic with the JAK2 inhibito