2. Academic Validation
  3. A novel selective multikinase inhibitor of ROCK and MRCK effectively blocks cancer cell migration and invasion

A novel selective multikinase inhibitor of ROCK and MRCK effectively blocks cancer cell migration and invasion

  • Cancer Lett. 2014 Nov 28;354(2):299-310. doi: 10.1016/j.canlet.2014.08.032.
Vijay Pralhad Kale 1,  Jeremy A Hengst 1,  Dhimant H Desai 1,  Taryn E Dick 1,  Katherine N Choe 1,  Ashley L Colledge 1,  Yoshinori Takahashi 1,  Shen-Shu Sung 1,  Shantu G Amin 1,  Jong K Yun 2
Affiliations

Affiliations

  • 1 Department of Pharmacology, Penn State Hershey College of Medicine, Hershey, PA 17033, USA.
  • 2 Department of Pharmacology, Penn State Hershey College of Medicine, Hershey, PA 17033, USA. Electronic address: jky1@psu.edu.
PMID: 25172415 DOI: 10.1016/j.canlet.2014.08.032
Abstract

Two structurally related protein kinase families, the Rho kinases (ROCK) and the myotonic dystrophy kinase-related Cdc42-binding kinases (MRCK) are required for migration and invasion of Cancer cells. We hypothesized that simultaneous targeting of these two kinase families might represent a novel therapeutic strategy to block the migration and invasion of metastatic cancers. To this end, we developed DJ4 as a novel small molecule inhibitor of these kinases. DJ4 potently inhibited activities of ROCK and MRCK in an ATP competitive manner. In cellular functional assays, DJ4 treatment significantly blocked stress fiber formation and inhibited migration and invasion of multiple Cancer cell lines in a concentration dependent manner. Our results strongly indicate that DJ4 may be further developed as a novel anti-metastatic chemotherapeutic agent for multiple cancers.

Keywords

Cancer; MRCK; Migration; Multikinase inhibitor; ROCK; Stress fibers.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-125221
    98.48%, ROCK/MRCKα/β Inhibitor