CAS |
No.150045-18-4 |
英文名称 |
MS-444 |
别名 |
BE-34776 |
分子式 |
C13H10O4 |
分子量 |
230.22 |
溶解性 |
Soluble in DMSO |
纯度 |
≥98% |
外观(性状) |
Light yellow to brown Solid |
储存条件 |
Powder:-20℃,2 years;Insolvent(母液):-20℃,6 months;-80℃,1 year |
运输条件 |
冷藏运输 |
MDL |
MFCD00923100 |
SMILES |
O=C(C1=C(C)OC=C1C2)C3=C2C(O)=CC=C3O |
InChIKey |
TZUYDLKHNQUNKS-UHFFFAOYSA-N |
InChI |
InChI=1S/C13H10O4/c1-6-11-7(5-17-6)4-8-9(14)2-3-10(15)12(8)13(11)16/h2-3,5,14-15H,4H2,1H3 |
PubChem CID |
132904 |
靶点 |
MLCK(myosin light chain kinase) |
通路 |
Cytoskeleton |
背景说明 |
MS-444是mLCK的抑制剂。 |
生物活性 |
MS-444 inhibits the activity of purified smooth muscle myosin light chain kinase (MLCK) with an IC50 value of 10 μM.[1-2] |
IC50 |
IC50: 10 μM (myosin)[1]. |
In Vitro |
MS-444 is a small molecule RNA-binding protein HuR (ELAVL1) inhibitor. Colorectal cancer (CRC) cells that display HuR overexpression are treated with MS-444 (1-100 μM) for 48 hr with IC50s of 10.98±1.76 μM, 12.84±2.10 μM, 5.60±0.90 μM, 14.21±2.11 μM, and 10.98±1.24 μM for HCT116, HCA-7, RKO, HT-29, and SW480 cells, respectively. Growth inhibition is observed in all CRC lines with IC50 values ranging from 5.60 μM to 14.21 μM with observable effects seen at 10 μM MS-444. Contrasting effects are observed using non-transformed small intestinal (RIE-1 (IC50=40.70±3.53 μM)) and colonic (YAMC (IC50=28.16±3.23 μM)) epithelial cells. Both cell types display properties of normal intestinal epithelial cells and are proficient in 3′UTR AU-rich elements (ARE)-mRNA decay. Both non-transformed cell lines are ~3- to 4-fold less responsive to MS-444-mediated growth inhibition, with IC50 values of 40.70 μM and 28.16 μM (P[2]. |
In Vivo |
To test the effects of MS-444 on CRC cell growth in vivo, mice bearing HCT116 cell xenografts receive IP injections of MS-444 (25 mg/kg bw) or vehicle every 48 hr. Over the experiment course, mice do not display any adverse effects and maintained similar weights. Anti-tumor effects of MS-444 are observed with approximately 1.7-fold reduction in tumor size. Mice treated with MS-444 show a marked 2- to 3-fold decrease in microvessel density (MVD), indicating the anti-angiogenic potential of MS-444[2]. |
细胞实验 |
Human colorectal cancer cell lines RKO, HCA-7, HCT116, HT-29, SW480 and the non-transformed intestinal epithelial cell lines RIE-1, YAMC are treated with varying concentrations of MS-444 (1-100 μM) for 48 hr. Cell survival is measured by MTT assay after incubation of cells for 48 hr with MS-444. Relative cell survival is calculated as percentage normalized to DMSO vehicle-treated cells and plotted to determine IC50[2]. |
动物实验 |
Mice[2]Athymic nude (Nu/Nu) mice are used. HCT116 (2×106 cells) and HCA-7 (2.5×106) cells resuspended in PBS are injected into the dorsal subcutaneous tissue. Mice (n=5 per group) receive intraperitoneal (IP) injections of MS-444 (25 mg/kg) dissolved in PBS/5% N-Methyl Pyrrolidine (NMP) or vehicle control every 48 hr. Tumor growth is assayed[2]. |
数据来源文献 |
[1]. Satoshi Nakanishi. et al. MS-444, a new inhibitor of myosin light chain kinase from Micromonosporasp.KY7123. The Journal Of Antibiotics. 1995,48(9):948-951. [2]. Fernando F. Blanco.et al, Impact of HuR inhibition by the small molecule MS-444 on colorectal cancer cell tumorigenesis. Oncotarget. 2016 Nov 8; 7(45): 74043-74058. |
规格 |
1mg |
单位 |
瓶 |