TAK-243-MLN7243-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemETAK-243Cat. No.: HY-100487CAS No.: 1450833-55-2Synonyms: MLN7243; AOB87172分式: CHFNOS分量: 519.52作靶点: E1/E2/E3 Enzyme; NF-B; Apoptosis作通路: Metabolic Enzyme/Protease; NF-B; Apoptosis储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C

2、6 months-20C 1 month溶解性数据体外实验 DMSO : 50 mg/mL (96.24 mM; Need ultrasonic)H2O : 1 mg/mL (1.92 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 1.9249 mL 9.6243 mL 19.2485 mL5 mM 0.3850 mL 1.9249 mL 3.8497 mL10 mM 0.1925 mL 0.9624 mL 1.9249 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

3、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 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (4.81 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.

4、5 mg/mL (4.81 mM); Clear solution1/3 Master of Small Molecules 您边的抑制剂师www.MedChemE3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.81 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 TAK-243种流的，选择性的泛素激活酶，UAE (UBA1) 抑制剂 (IC50=1 nM)，其阻断了泛素结合，破坏了单泛素信号传导和全蛋泛素化。TAK-243 诱导内质应激 (ER) 反应，消除 NF-B 通路活化，促进细

5、胞凋亡 1 2。IC50 & Target IC50: 1 nM (UBA1) 1体外研究 TAK-243 shows anti-proliferative effect on a panel of cell lines derived from hematologic and solid tumorswith variable EC50 values that ranged from 0.006 M to 1.31 M 1.TAK-243 reduces growth and viability of human AML cell lines (OCI-AML2, TEX, U937 and

6、 NB4) in aconcentration- and time-dependent manner with IC50s ranging from 15-40 nM after treatment for 48 hours3.体内研究 TAK-243 significantly delays tumor growth in mice (T/C=0.02) with no toxicity as evidenced by no changes inmouse body weight, serum chemistry, or organ histology. TAK-243 reduces pr

7、imary AML tumor burden inboth tested samples without toxicity 3.PROTOCOLCell Assay 1 Normal keratinocytes (normal human keratinocytes (NHK) and recessive dystrophic epidermolysis bullosakeratinocytes (RDEBK) and cSCC cell lines are seeded into 96 well plates and live cell number and celldeath are an

8、alysed with an IncuCyte ZOOM real-time imager using the CellTox Green Cytotoxicity Assay.Relative EC50 values are determined using GraphPad Prism. For clonogenic assays cells are seeded intosix well plates. Inhibitors (e.g., TAK-243; 0.01, 0.1, 1, and 10 M) are added for the indicated times and then

9、cells are maintained in drug-free medium for up to 2 weeks to allow colony formation. Colonies are fixed in10% methanol, 10% acetic acid and stained with crystal violet 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 2Administration 2 The

10、preclinical efficacy and toxicity of TAK-243 are assessed in mouse models of AML. OCI-AML2 cells areinjected subcutaneously (sc) into SCID mice, and when tumors are palpable, mice are treated with TAK-243(20 mg/kg sc twice weekly). As an additional model, primary AML cells from 2 patients are inject

11、ed into thefemurs of NOD-SCID mice. Two weeks after injection, mice are treated with TAK-243 (20 mg/kg sc twiceweekly). After 3 weeks of treatment, mice ae sacrificed, and AML engraftment in the non-injected femur ismeasured by flow cytometry 2.MCE has not independently confirmed the accuracy of the

12、se methods. They are for reference only.户使本产品发表的科研献2/3 Master of Small Molecules 您边的抑制剂师www.MedChemE J Biol Chem. 2019 Aug 2. pii: jbc.RA119.009654.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Hyer ML, et al. A small-molecule inhibitor of the ubiquitin activating enzyme for

13、cancer treatment. Nat Med. 2018 Feb;24(2):186-193.2. Best SR, et al. TAK-243, a small molecule inhibitor of ubiquitin-activating enzyme (UAE), induces ER stress and apoptosis in diffuselarge B-cell lymphoma (DLBCL) cells. Blood 2017 130:1533.3. Samir H. Barghout, et al. TAK-243 Is a Selective UBA1 Inhibitor That Displays Preclinical Activity in Acute Myeloid Leukemia (AML).Blood 2017, 130:814.Mc