Inhibiting Hedgehog - An update on pharmacological compounds and targeting strategies.

08:00 EDT 15th April 2019 | BioPortfolio

Summary of "Inhibiting Hedgehog - An update on pharmacological compounds and targeting strategies."

Important steps in embryonic development are governed by the Hedgehog (Hh) signaling pathway, an evolutionary conserved signal transduction cascade. However, Hh activity is not only crucial during embryo formation, but is also involved in adult tissue repair and in several malignancies. Particularly due to its link to cancer, small molecule Hh pathway inhibitors have been developed and the first compounds have been approved for use in Hh-driven basal cell carcinoma. Almost all advanced Hh inhibitors target the critical signaling component Smoothened (SMO), but pre-clinical research has identified additional compounds which can block the Hh pathway along its entire signaling cascade, which, in light of emerging drug resistance occurring with SMO inhibitors, is of high importance. Herein we give an overview on currently known Hh pathway inhibitors, delineating their respective strengths and weaknesses and describing potential drug targeting strategies to interfere with Hh signaling in different cancer settings.


Journal Details

This article was published in the following journal.

Name: Journal of medicinal chemistry
ISSN: 1520-4804


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Medical and Biotech [MESH] Definitions

A frizzled-like, G-protein-coupled receptor that associates with PATCHED RECEPTORS to transduce signals from HEDGEHOG PROTEINS and initiate hedgehog signaling to ZINC FINGER PROTEIN GLI1. It may normally inhibit signaling in the absence of SONIC HEDGEHOG PROTEIN binding to PATCHED RECEPTOR-1.

A family of intercellular signaling proteins that play and important role in regulating the development of many TISSUES and organs. Their name derives from the observation of a hedgehog-like appearance in DROSOPHILA embryos with genetic mutations that block their action.

Systems for the delivery of drugs to target sites of pharmacological actions. Technologies employed include those concerning drug preparation, route of administration, site targeting, metabolism, and toxicity.

A patched receptor for several HEDGEHOG PROTEINS that associates with the SMOOTHENED RECEPTOR to modulate hedgehog signaling. It is also a TUMOR SUPPRESSOR PROTEIN; mutations in the patched-1 gene are associated with BASAL CELL NEVUS SYNDROME; SQUAMOUS CELL CARCNIOMA of the ESOPHAGUS; trichoepitheliomas, and CARCINOMA, TRANSITIONAL CELL of the URINARY BLADDER.

A cytoplasmic receptor and peroxin that contains a series of TETRACOTIPEPTIDE REPEATS and binds to PEROXISOME TARGETING SIGNAL 1 (SKL-type). It is essential for protein import into PEROXISOMES; mutations in the PEX5 gene are associated with PEROXISOMAL DISORDERS such as ZELLWEGER SYNDROME.

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