MI-463 - Epigenetic Reader Domain 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEMI-463Cat. No.: HY-19809CAS No.: 1628317-18-9分式: CHFNS分量: 484.54作靶點: Epigenetic Reader Domain作通路: Epigenetics儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 125 mg/mL (257.98 mM; Need ultra

2、sonic)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.08 mg/mL (4.29 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.08 mg/mL (4.29 mM); Suspended solution; Need ultrasonic3. 請依序添加每種溶劑： 10% DMSO 90% corn oil1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemESolub

3、ility: 2.08 mg/mL (4.29 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 MI-463效，有服活性的menin-mLL相互作的分抑制劑。體外研究 MI-463 can reach the target protein in mammalian cells and effectively inhibit the menin-mLL-AF9 interactionat sub-micromolar concentrations. Treatment of murine bone marrow cells (BMC) transformed

4、with the mLL-AF9 oncogene with MI-463 results in substantial growth inhibition, with GI50 of 0.23 M 1.體內(nèi)研究 MI-463 achieves high level in peripheral blood following a single intravenous or oral dose, while also showinghigh oral bioavailability (45%). Pharmacologic inhibition of the menin-mLL interact

5、ion substantially delaysprogression of mLL leukemia in murine models through on-target activity without causing toxicity. MI-463induces strong inhibition of tumor growth with once daily intraperitoneal (i.p.) administration. The expressionof mLL fusion protein target genes, HOXA9 and MEIS1, are sign

6、ificant reduced upon treatment with MI-463.20 days treatment of MV4;11 xenograft recipient mice with MI-463 also results in a substantial delay inleukemia progression as manifested by a marked decrease in the bioluminescence level which is associatedwith a significant decrease in the population of l

7、eukemic cells in the peripheral blood, spleen and bonemarrow samples 1.PROTOCOLCell Assay 1 Leukemia cells are treated with MI-463 or 0.25% DMSO and cultured at 37 C for 7 days. Media is changedat day 4, viable cell numbers are restored to the original concentration and MI-463 are re-supplied. MTT c

8、ellproliferation assay kit is then employed, and plates are read for absorbance at 570 nm using a microplatereader 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice: For efficacy studies in MV4;11 subcutaneous xenograft mice model, 5106 cell

9、s are injected into the 4-Administration 1 6 week old female BALB/c nude mice. Treatment is started when the tumor size reached 100 mm3. Vehicle(25% DMSO, 25% PEG400, 50% PBS) or compounds (MI-463 or MI-503) are administrated once daily atdesignated doses using i.p. injections 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Borkin D, et al. Pharmacologic inhibition of the Menin-MLL interaction blocks progression of MLL leukemia in vivo. Cancer Cell. 2015 Apr13;27(4):589-602.McePdfHeightCaution: Product has not been fully validat