Unknown

Dataset Information

0

Isothiocyanatostilbenes as novel c-Met inhibitors.

ABSTRACT: The hepatocyte growth factor receptor (HGFR or c-Met) is a driver of multiple cancer subtypes. While there are several c-Met inhibitors in development, few have been approved for clinical use, warranting the need for continued research and development of c-Met targeting therapeutic modalities. The research presented here demonstrates a particular class of compounds known as isothiocyanatostilbenes can act as c-Met inhibitors in multiple cancer cell lines. Specifically, we found that 4,4'-Diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) and 4,4'-Diisothiocyanatodihydrostilbene-2,2'-disulfonic acid (H2DIDS) had c-Met inhibitory effective doses in the low micromolar range while 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS) and 4,4'-dinitrostilbene-2, 2'-disulfonic acid (DNDS) exhibited IC50s 100 to 1000 fold higher. These compounds displayed much greater selectivity for inhibiting c-Met activation compared to similar receptor tyrosine kinases. In addition, DIDS and H2DIDS reduced hepatocyte growth factor (HGF)-induced, but not epidermal growth factor (EGF)-induced, cell scattering, wound healing, and 3-dimensional (3D) proliferation of tumor cell spheroids. In-cell and cell-free assays suggested that DIDS and H2DIDS can inhibit and reverse c-Met phosphorylation, similar to SU11274. Additional data demonstrated that DIDS is tolerable in vivo. These data provide preliminary support for future studies examining DIDS, H2DIDS, and derivatives as potential c-Met therapeutics.

SUBMITTER: Gray AL 

PROVIDER: S-EPMC4747398 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Isothiocyanatostilbenes as novel c-Met inhibitors.

Gray Alana L AL   Coleman David T DT   Castore Reneau F RF   Mohyeldin Mohamed M MM   El Sayed Khalid A KA   Cardelli James A JA  

Oncotarget 20151201 38

The hepatocyte growth factor receptor (HGFR or c-Met) is a driver of multiple cancer subtypes. While there are several c-Met inhibitors in development, few have been approved for clinical use, warranting the need for continued research and development of c-Met targeting therapeutic modalities. The research presented here demonstrates a particular class of compounds known as isothiocyanatostilbenes can act as c-Met inhibitors in multiple cancer cell lines. Specifically, we found that 4,4'-Diisoth  ...[more]

Similar Datasets

Unknown Discovery and Biological Evaluation of Novel Dual EGFR/c-Met Inhibitors.
| S-EPMC4027597 | biostudies-literature
Unknown Synthesis of novel 6,7-dimethoxy-4-anilinoquinolines as potent c-Met inhibitors.
| S-EPMC6237173 | biostudies-literature
Unknown Discovery of novel c-Met inhibitors bearing a 3-carboxyl piperidin-2-one scaffold.
| S-EPMC6271681 | biostudies-literature
Unknown MET-GRB2 Signaling-Associated Complexes Correlate with Oncogenic MET Signaling and Sensitivity to MET Kinase Inhibitors.
| S-EPMC5833309 | biostudies-literature
Unknown Phenanthrotriazine Derivatives Containing Arylidine Hydrazone Moieties as Novel Potential c-Met Inhibitors with Anticancer Effect.
| S-EPMC8653689 | biostudies-literature
Unknown MET amplification identified by next-generation sequencing and its clinical relevance for MET inhibitors.
| S-EPMC8579577 | biostudies-literature
Unknown (1S,2E,4S,7E,11E)-2,7,11-Cembratriene-4,6-diol semisynthetic analogs as novel c-Met inhibitors for the control of c-Met-dependent breast malignancies.
| S-EPMC5079820 | biostudies-literature
Unknown Design, Synthesis, and Biological Evaluation of Novel Imidazo[1,2-a]pyridine Derivatives as Potent c-Met Inhibitors.
| S-EPMC4434476 | biostudies-literature
Unknown Discovery of Potent, Selective Triazolothiadiazole-Containing c-Met Inhibitors.
| S-EPMC8201751 | biostudies-literature
Unknown Safety and Tolerability of c-MET Inhibitors in Cancer.
| S-EPMC7491978 | biostudies-literature