Document Detail

Hedgehog pathway inhibitors: a patent review (2009--present).
MedLine Citation:
PMID:  23294277     Owner:  NLM     Status:  MEDLINE    
INTRODUCTION: The hedgehog (Hh) pathway is a developmental signaling pathway that plays a key role in directing cellular growth and tissue patterning during embryonic development. Dysregulation of Hh signaling has been linked to the development of a variety of human tumors, and numerous drug development programs in both academia and industry are actively exploring inhibitors of the pathway as anti-cancer agents.
AREAS COVERED: This review surveys the recent patent literature (2009 - 2012) for Hh pathway inhibitors as treatments for a variety of human malignancies.
EXPERT OPINION: To date, all of the pathway inhibitors that have entered clinical trials and the majority of compounds identified via high-throughput screens target smoothened (Smo), a transmembrane protein that is essential for pathway signaling. While these compounds have shown initial promise in preclinical and clinical trials, several mechanisms of resistance to Smo inhibitors have been identified. Even with this knowledge, the majority of small-molecule pathway inhibitors disclosed in the recent patent literature directly target Smo. The continued identification of Hh pathway inhibitors that function either upstream or downstream is warranted not only to combat these emerging resistance mechanisms, but also to help elucidate the various cellular mechanisms that control both normal and oncogenic pathway signaling.
Matthew Kyle Hadden
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2013-01-08
Journal Detail:
Title:  Expert opinion on therapeutic patents     Volume:  23     ISSN:  1744-7674     ISO Abbreviation:  Expert Opin Ther Pat     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-15     Completed Date:  2013-08-09     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  9516419     Medline TA:  Expert Opin Ther Pat     Country:  England    
Other Details:
Languages:  eng     Pagination:  345-61     Citation Subset:  IM    
Department of Pharmaceutical Sciences, University of Connecticut, 69 N Eagleville Rd, Unit 3092, Storrs, CT 06269-3092, USA
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MeSH Terms
Antineoplastic Agents / chemistry,  pharmacology*,  therapeutic use
Brain Neoplasms / drug therapy
Hedgehog Proteins / antagonists & inhibitors*,  physiology
Medulloblastoma / drug therapy
Patents as Topic
Receptors, G-Protein-Coupled / drug effects
Signal Transduction / drug effects*
Structure-Activity Relationship
Reg. No./Substance:
0/Antineoplastic Agents; 0/Hedgehog Proteins; 0/Receptors, G-Protein-Coupled; 0/SMO protein, human

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