Book chapter
Inhibitors of K-Ras Plasma Membrane Localization
Inhibitors of the Ras Superfamily G-proteins, Part A, pp.249-265
The Enzymes, v. 33, Academic Press
2013
DOI: 10.1016/B978-0-12-416749-0.00011-7
PMID: 25033808
Abstract
Oncogenic mutant K-Ras is highly prevalent in multiple human tumors. Despite significant efforts to directly target Ras activity, no K-Ras-specific inhibitors have been developed and taken into the clinic. Since Ras proteins must be anchored to the inner leaflet of the plasma membrane (PM) for full biological activity, we devised a high-content screen to identify molecules with ability to displace K-Ras from the PM. Here we summarize the biochemistry and biology of three classes of compound identified by this screening method that inhibit K-Ras PM targeting: staurosporine and analogs, fendiline, and metformin. All three classes of compound significantly abrogate cell proliferation and Ras signaling in K-Ras-transformed cancer cells. Taken together, these studies provide an important proof of concept that blocking PM localization of K-Ras is a tractable therapeutic target.
Details
- Title: Subtitle
- Inhibitors of K-Ras Plasma Membrane Localization
- Creators
- Kwang-jin Cho - Department of Integrative Biology and Pharmacology, The University of Texas Medical School at Houston, Houston, Texas, USADharini van der Hoeven - Department of Diagnostic and Biomedical Sciences, The University of Texas School of Dentistry at Houston, Houston, Texas, USAJohn F. Hancock - Texas Medical Center
- Resource Type
- Book chapter
- Publication Details
- Inhibitors of the Ras Superfamily G-proteins, Part A, pp.249-265
- Series
- The Enzymes; v. 33
- DOI
- 10.1016/B978-0-12-416749-0.00011-7
- PMID
- 25033808
- eISSN
- 1874-6047
- ISSN
- 1874-6047
- Publisher
- Academic Press; Waltham, MA
- Number of pages
- 17
- Language
- English
- Date published
- 2013
- Academic Unit
- Oral Pathology, Radiology and Medicine; Dentistry Administration
- Record Identifier
- 9985157463802771
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