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MLN9708

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Chemical Structure| 1201902-80-8 同义名 : -
CAS号 : 1201902-80-8
货号 : A428391
分子式 : C20H23BCl2N2O9
纯度 : 99%
分子量 : 517.122
MDL号 : MFCD18251437
存储条件：

粉末 Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 : -
动物实验配方：

IP 2% DMSO+2% Tween80+30% PEG300+water 9 mg/mL clear

PO 0.5% CMC-Na 41 mg/mL suspension

生物活性
靶点

  • 20S proteasome

    20S proteasome, Ki:0.93 nM

    20S proteasome, IC50:3.4 nM
描述 The proteasome is a highly sophisticated protease complex responsible for degradation of intracellular proteins. The proteasome collaborates with ubiquitin is the principal manner by which cells regulate protein homeostasis[3]. MLN9708 is a selective, potent, and reversible inhibitor of proteasome, and can be hydrolyzed to pharmacologically active ML2238, which inhibits the chymotrypsin-like β5 proteolytic site of the 20S proteasome with IC50 value of 3.4 nM. In addition, MLN2238 inhibits the caspase-like β1 and trypsin-like β2 proteolytic sites with IC50 values of 31 nM and 3.5 μM, respectively[4]. In vitro, MLN2238 strongly inhibited TNF-α-induced activation of the NF-κB pathway with EC50 value of 55 nM in HEK293 cells. MLN2238 can inhibit cell proliferation, including A375, H460, HCT116 and HT-29 cell lines, with LD50 values ranging in 4 – 58 nM, suggesting MLN9708 has potent anti-proliferative effect on lung and colon tumor[4]. MLN2238 predominantly inhibited chymotrypsin-like activity of the proteasome and induced accumulation of ubiquitinated proteins in Multiple Myeloma cells. MLN2238 inhibited growth and induces apoptosis in Multiple Myeloma cell lines MM.1S, INA-6, RPMI-8226, MM.1R, H929, OPM1, and OPM2 at concentration ranging 6.25 nM - 50 nM, suggesting that MLN9708 have activity of the against Multiple Myeloma cells[5]. In vivo, administered MLN2238 both intravenous injection at 14 mg/kg twice weekly or subcutaneous injection 4 mg/kg once daily showed strong antitumor activity and generated a greater apoptotic response in tumor tissue of CB17-SCID mice bearing WSU-DLCL2 xenografts[4]. Administered MLN2238 at 11 mg/kg via intravenous injection twice weekly for 3 weeks inhibited human Multiple Myeloma cell growth in vivo and prolongs survival in human plasmacytoma MM.1S xenograft mice model[6].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.93mL

0.39mL

0.19mL

9.67mL

1.93mL

0.97mL

19.34mL

3.87mL

1.93mL
参考文献

[1]85(1):12-36.

[2]70(5):1970-80.

[3]Tanaka K. The proteasome: overview of structure and functions. Proc Jpn Acad Ser B Phys Biol Sci. 2009;85(1):12-36.

[4]Kupperman E, Lee EC, Cao Y, Bannerman B, Fitzgerald M, Berger A, Yu J, Yang Y, Hales P, Bruzzese F, Liu J, Blank J, Garcia K, Tsu C, Dick L, Fleming P, Yu L, Manfredi M, Rolfe M, Bolen J. Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Cancer Res. 2010 Mar 1;70(5):1970-80.