Pimasertib-AS703026-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEPimasertibCat. No.: HY-12042CAS No.: 1236699-92-5Synonyms: AS703026; MSC1936369B分式: CHFINO分量: 431.2作靶点: MEK作通路: MAPK/ERK Pathway储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 100 mg/mL (23

2、1.91 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.3191 mL 11.5955 mL 23.1911 mL5 mM 0.4638 mL 2.3191 mL 4.6382 mL10 mM 0.2319 mL 1.1596 mL 2.3191 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

3、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 (5.80 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.80 mM); Clear solution1/3 Master of Small Molecules 您

4、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 (5.80 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Pimasertib (AS703026)种效，具有选择性，ATP 竞争性的 MEK1/2 别构抑制剂，主 于癌症研究。IC50 & Target MEK1 MEK2体外研究 Pimasertib (5, 0.5, and 0.1 M) specifically blocks ERK1/2 activation in MM cells, culture

5、d alone or withBMSCs. Pimasertib inhibits the growth of MM cell lines in a dose-dependent manner, with IC50s rangingfrom 0.005 to 2 M. The IC50s of Pimasertib against INA-6, U266, H929 cells are 10 nM, 5 nM, 200 nMrespectively. Pimasertib induces apoptosis and modulates the cell cycle profile. Pimas

6、ertib targets MM cellsin the BM microenvironment 1. Pimasertib (10 mol/L) inhibits ERK pathway, proliferation, andtransformation in cetuximab-resistant D-MUT cells 2. Pimasertib in combination with PLX4032 significantlyinduces apoptosis of RPMI-7951 cells, whereas each drug used alone does not. Pima

7、sertib synergizes withsmall interfering RNA-mediated downregulation of BRAF to produce results similar to those of combinedtreatment with PLX4032 and Pimasertib 3.体内研究 Pimasertib (15, 30 mg/kg) significantly inhibits the growth of tumor in the human H929 MM xenograft modelin CB17 SCID mice 1. Pimase

8、rtib (10 mg/kg, p.o.) inhibits tumor growth of cetuximab-resistant tumorattributed by K-ras mutation 2.PROTOCOLCell Assay 1 The inhibitory effects of study compounds on MM cell growth and survival are assessed by both3Hthymidine incorporation and by measuring MTT dye absorbance. Cells (104/well for

9、MM cell line, intriplicates and 2-5105/well for patient MM cells) are cultured in 96-well plates for 3 days (MM cell lines) or 5-days (patient MM cells). For the 3Hthymidine incorporation assay, cells are pulsed with 0.5 Ci (0.0185MBq)/well 3Hthymidine for 6 h (cell lines), harvested onto glass fibe

10、r filters, and counted in a -scintillationcounter. Due to low DNA synthesis of patient MM cells, they are pulsed with 2 Ci/well 3Hthymidine andmeasured during the last 36 h of culture.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal CB17 severe co

11、mbined immunodeficiency (SCID) mice are subcutaneously inoculated with H929 (4106)Administration 1 cells in 100 L RPMI-1640 medium. Mice developed palpable tumors (appr 130 mm3) approximately 3weeks after cell injection and are randomized to receive orally twice daily either Pimasertib (15 or 30 mg/

12、kg)or control vehicle alone. Tumor size is measured every other day in 2 dimensions using calipers, and tumorvolume is calculated. Animals are euthanized when their tumors reach 2 cm3 in volume, when they aremoribund or show paralysis or major compromise in their quality of life occurs. Tumor format

13、ion changes inmice treated with control vehicle vs. Pimasertib are plotted using the GraphPad Prism version 4.03 for2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEWindows. Tumors are subjected to immunoblotting and immunochemistry analyses using specificmonoclonal (m)Abs. Images are examined with

14、a Leica DM LB research microscope, captured using LeicaIM50 Image Manager, and processed using Adobe Photoshop Software version 7.0.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 Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093.See more c

15、ustomer validations on HYPERLINK / www.MedChemEREFERENCES1. Kim K, et al. Blockade of the MEK/ERK signalling cascade by AS703026, a novel selective MEK1/2 inhibitor, induces pleiotropic anti-myeloma activity in vitro and in vivo. Br J Haematol, 2010, 149(4), 537-549.2. Yoon J, et al. MEK1/2 inhibito

16、rs AS703026 and AZD6244 may be potential therapies for KRAS mutated colorectal cancer that isresistant to EGFR monoclonal antibody therapy. Cancer Res, 2011, 71(2), 445-453.3. Park SJ, et al. The MEK1/2 inhibitor AS703026 circumvents resistance to the BRAF inhibitor PLX4032 in human malignant melanomacel