Fimepinostat-CUDC-907-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEFimepinostatCat. No.: HY-13522CAS No.: 1339928-25-4Synonyms: CUDC-907分式: CHNOS分量: 508.55作靶点: PI3K; HDAC作通路: PI3K/Akt/mTOR; Cell Cycle/DNA Damage; Epigenetics储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶

2、解性数据体外实验 DMSO : 50 mg/mL (98.32 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 1.9664 mL 9.8319 mL 19.6637 mL5 mM 0.3933 mL 1.9664 mL 3.9328 mL10 mM 0.1966 mL 0.9832 mL 1.9664 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验 请根据您的实验动物和给药式选择适当的溶解案，配制前请

3、先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (4.92 mM); Clear solution; Need ultrasonic2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.92 mM); Clear solution1/3 Mast

4、er of Small Molecules 您边的抑制剂师www.MedChemEBIOLOGICAL ACTIVITY物活性 Fimepinostat (CUDC-907) 有效抑制 I 型 PI3K 及 I 和 II 型 HDAC 酶，作于 PI3K/PI3K/PI3K 和HDAC1/HDAC2/HDAC3/HDAC10 ，IC50 分别为 19/54/39 nM 和 1.7/5.0/1.8/2.8 nM。IC50 & Target PI3K PI3K PI3K PI3K19 nM (IC50) 39 nM (IC50) 54 nM (IC50) 311 nM (IC50)HDAC1 HD

5、AC3 HDAC10 HDAC21.7 nM (IC50) 1.8 nM (IC50) 2.8 nM (IC50) 5 nM (IC50)HDAC11 HDAC6 HDAC8 HDAC45.4 nM (IC50) 27 nM (IC50) 191 nM (IC50) 409 nM (IC50)HDAC7 HDAC9 HDAC5426 nM (IC50) 554 nM (IC50) 674 nM (IC50)体外研究 Fimepinostat is a potent pan-inhibitor of HDAC classes I and II enzymes and observed that

6、its potencyagainst class I HDACs is similar to that of LBH589 and greater than that of SAHA. Fimepinostat is also apotent inhibitor of class I PI3K kinases with an IC50 of 19, 54, and 39 nM for PI3K, PI3K, and PI3K,respectively. Fimepinostat markedly induces p21 protein in H460, a non-small cell lun

7、g cancer (NSCLC) cellline. Fimepinostat causes the reduction of both p-STAT3 (Y-705) and p-SRC in RPMI-8226 multiple myelomacells and reduces both phosphorylated and total protein levels of MET and EGFR as well as HER2 andHER3 in H1975 NSCLC cells and BT-474 breast cancer cells, respectively. Fimepi

8、nostat induces caspase-3and -7 activation in HCT-116 colon cancer cells in a dose-dependent manner. Fimepinostat potently inhibitsthe growth of cancer cells derived from both hematologic and solid tumors. Fimepinostat potently inhibits theproliferation of cells expressing either mutant or wild-type

9、PI3K 1.体内研究 Oral administration of Fimepinostat inhibits growth of the Daudi cancer cell xenografts in a dose-dependentmanner. Tumor stasis is observed at 100 mg/kg in this model without obvious toxicity. Importantly, in thesame model, Fimepinostat achieves better efficacy than GDC-0941, SAHA, or a

10、combination of these 2compounds given at their maximal tolerated doses (MTD). Furthermore, Fimepinostat causes tumorregression or stasis after intravenous (50 mg/kg) or oral administration (100 mg/kg) in a xenograft tumormodel of SU-DHL4 diffuse large B-cell lymphoma (DLBCL) and causes tumor stasis

11、in KRAS-mutant A549NSCLC cell xenografts 1.PROTOCOLKinase Assay 1 The activities of classes I and II HDACs are measured using the Color-de-Lys assay system. The activity ofPI3K is measured using the ADP-Glo luminescent kinase assay. Recombinant PI3K protein, a complex of N-terminal GST-tagged recomb

12、inant full-length human p110 and untagged recombinant full-length human p85,is coexpressed in a baculovirus-infected Sf9 cell expression system 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemECell Assay

13、 1 Human cancer cell lines are plated at densities of 5,000 to 10,000 per well in 96-well flat-bottomed plateswith the recommended culture medium. The cells are then incubated with compounds (e.g.,Fimepinostat) atvarious concentrations for 72 hours in culture medium supplemented with 0.5% (v/v) FBS.

14、 Growth inhibitionis assessed by assay of cellular ATP content using the Perkin-Elmer ATPlite kit 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 1Administration 1 Six- to 8-week-old female athymic (nude nu/nu CD-1) or severe combined immu

15、nodeficient (SCID) miceobtained from Charles River Laboratories are injected subcutaneously with 3 to 20106 cells in a mediumsuspension of 100 to 200 L into the right hind flank region. Varying doses of Fimepinostat, standardanticancer agents, or vehicle are administered orally or via tail vein inje

16、ction as indicated.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Acta Pharmacol Sin. 2019 May;40(5):677-688 ACS Med Chem Lett. 2015 Jun 22;6(8):948-52. Harvard Medical School LINCS LIBRARYSee more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Qian C, et al. Cancer network disruption by a single molecule inhibitor targeting both histone deacetylase activity andphosphatidylinositol 3-kinase signa