Document Detail


Recent patents for Hedgehog pathway inhibitors for the treatment of malignancy.
MedLine Citation:
PMID:  19505195     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: There is increasing evidence suggesting that blocking aberrant Hedgehog (Hh) signaling can be a novel therapeutic avenue for the treatment of cancer. During the past decade, efforts from academic and industrial groups have led to the discovery of a variety of Hh pathway inhibitors. OBJECTIVE: This review covers the patent literature related to Hh pathway inhibitors for the treatment of proliferative diseases, regardless of their modes of action. METHODS: A comprehensive survey of the patent literature since 1999 is presented. RESULTS/CONCLUSION: Most reported Hh pathway inhibitors act on the key signaling transducer Smoothened (SMO). Screening of compound libraries using reporter and binding assays have identified a broad diversity of chemical structures that interact with SMO. These screening approaches, followed by conventional medicinal chemistry, have delivered important clinical drug candidates, such as GDC-0449 and XL-139. In addition, modification of the naturally occurring Veratrum alkaloid cyclopamine has resulted in various active analogues, including clinical drug candidate IPI-926. Although there are recent scientific literature reports of small molecules acting downstream of SMO, there is limited patent literature on this mode of Hh pathway inhibition.
Authors:
Martin R Tremblay; Michael Nesler; Robin Weatherhead; Alfredo C Castro
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Expert opinion on therapeutic patents     Volume:  19     ISSN:  1744-7674     ISO Abbreviation:  Expert Opin Ther Pat     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-07-29     Completed Date:  2009-11-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9516419     Medline TA:  Expert Opin Ther Pat     Country:  England    
Other Details:
Languages:  eng     Pagination:  1039-56     Citation Subset:  IM    
Affiliation:
Infinity Pharmaceuticals, Inc., Cambridge, MA 02139, USA. Martin.Tremblay@infi.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / pharmacology,  therapeutic use*
Biological Products / pharmacology
Hedgehog Proteins / antagonists & inhibitors*,  physiology
Heterocyclic Compounds / pharmacology
Humans
Neoplasms / drug therapy*
Patents as Topic
RNA Interference
Signal Transduction / drug effects*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Biological Products; 0/Hedgehog Proteins; 0/Heterocyclic Compounds

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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