TAK-243-MLN7243-DataSheet-生命科學(xué)試劑-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作靶點: E1/E2/E3 Enzyme; NF-B; Apoptosis作通路: Metabolic Enzyme/Protease; NF-B; Apoptosis儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C

2、6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 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制備儲備液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

3、保存式和期限。體內(nèi)實驗請根據(jù)您的實驗動物和給藥式選擇適當?shù)娜芙獍?，配制前請先配制澄清的儲備液，再依次添加助溶?為保證實驗結(jié)果的可靠性，體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當天使；澄清的儲備液可以根據(jù)儲存條件，適當保存；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: 2.5 mg/mL (4.81 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.

4、5 mg/mL (4.81 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.81 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 TAK-243種流的，選擇性的泛素激活酶，UAE (UBA1) 抑制劑 (IC50=1 nM)，其阻斷了泛素結(jié)合，破壞了單泛素信號傳導(dǎo)和全蛋泛素化。TAK-243 誘導(dǎo)內(nèi)質(zhì)應(yīng)激 (ER) 反應(yīng)，消除 NF-B 通路活化，促進細

5、胞凋亡 1 2。IC50 & Target IC50: 1 nM (UBA1) 1體外研究 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.體內(nèi)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.戶使本產(chǎn)品發(fā)表的科研獻2/3 Master of Small Molecules 您邊的抑制劑師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