Recent patents for Hedgehog pathway inhibitors for the treatment of malignancy
| Autor: | Martin R Tremblay, Michael Nesler, Robin Weatherhead, Alfredo C Castro |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Drug
Patched Cyclopamine media_common.quotation_subject Antineoplastic Agents Pharmacology Biology Patents as Topic chemistry.chemical_compound Heterocyclic Compounds Neoplasms Drug Discovery medicine Animals Humans Hedgehog Proteins Hedgehog media_common Biological Products Natural product Cancer General Medicine medicine.disease Hedgehog signaling pathway chemistry Cancer research RNA Interference Smoothened Signal Transduction |
| Zdroj: | Expert Opinion on Therapeutic Patents. 19:1039-1056 |
| ISSN: | 1744-7674 1354-3776 |
| DOI: | 10.1517/13543770903008551 |
| Popis: | 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.This review covers the patent literature related to Hh pathway inhibitors for the treatment of proliferative diseases, regardless of their modes of action.A comprehensive survey of the patent literature since 1999 is presented.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. |
| Databáze: | OpenAIRE |
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