Met receptor inhibitor SU11274 localizes in the endoplasmic reticulum

Edwin J Wiest; Heather Jensen Smith; Michael A Hollingsworth

doi:10.1016/j.bbrc.2018.05.034

Met receptor inhibitor SU11274 localizes in the endoplasmic reticulum

Biochem Biophys Res Commun. 2018 Jul 2;501(4):858-862. doi: 10.1016/j.bbrc.2018.05.034. Epub 2018 May 19.

Authors

Edwin J Wiest¹, Heather Jensen Smith², Michael A Hollingsworth³

Affiliations

¹ Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA; Eppley Institute, Fred and Pamela Buffet Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
² Eppley Institute, Fred and Pamela Buffet Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
³ Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA; Eppley Institute, Fred and Pamela Buffet Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA. Electronic address: mahollin@unmc.edu.

Abstract

We discovered that SU11274, a class I c-Met inhibitor, fluoresces when excited by 488 nm laser light and showed rapid specific accumulation in distinct subcellular compartments. Given that SU11274 reduces cancer cell viability, we exploited these newly identified spectral properties to determine SU11274 intracellular distribution and accumulation in human pancreatic cancer cells. The aim of the studies reported here was to identify organelle(s) to which SU11274 is trafficked. We conclude that SU11274 rapidly and predominantly accumulates in the endoplasmic reticulum.

Keywords: Endoplasmic reticulum; SU11274; Sulfonylurea receptor; Unfolded protein response.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Biological Transport / drug effects
Cell Line, Tumor
Endoplasmic Reticulum / drug effects
Endoplasmic Reticulum / metabolism*
Fluorescence
Humans
Indoles / chemistry
Indoles / metabolism*
Indoles / pharmacology*
Piperazines / chemistry
Piperazines / metabolism*
Piperazines / pharmacology*
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / metabolism*
Protein Kinase Inhibitors / pharmacology*
Proto-Oncogene Proteins c-met / antagonists & inhibitors*
Proto-Oncogene Proteins c-met / metabolism
Subcellular Fractions / drug effects
Subcellular Fractions / metabolism
Sulfonamides / chemistry
Sulfonamides / metabolism*
Sulfonamides / pharmacology*

Substances

((3Z)-N-(3-chlorophenyl)-3-((3,5-dimethyl-4-((4-methylpiperazin-1-yl)carbonyl)-1H-pyrrol-2-yl)methylene)-N-methyl-2-oxo-2,3-dihydro-1H-indole-5-sulfonamide)
Indoles
Piperazines
Protein Kinase Inhibitors
Sulfonamides
Proto-Oncogene Proteins c-met

Abstract

Publication types

MeSH terms

Substances

Grants and funding