MS-444

Research use only, not for human use.

MS-444 (BE-34776) is a smooth muscle myosin light chain kinase (MLCK) and HuR inhibitor with antitumor activity for triple-negative breast and colorectal cancer.

MS-444 inhibits the activity of purified smooth muscle myosin light chain kinase (MLCK) with an IC50 value of 10 μM.

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<0.05).

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 inmicrovessel density (MVD), indicating the anti-angiogenic potential of MS-444.

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Cytoskeleton/Cell Adhesion Molecules

Myosin

Myosin | Serine/threonin kinase

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150045-18-4

230.22

C13H10O4

>98% (HPLC)

In Vitro:?DMSO : 50 mg/mL (217.18 mM; Ultrasonic )1-Methyl-2-pyrrolidinone : 20 mg/mL (86.87 mM; Ultrasonic)

O=C1C=2C(O)=CC=C(O)C2CC3=COC(=C13)C

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(-20℃)

With Ice Pack

≥ 2 years