Current Status of Hedgehog Signaling Inhibitors

Xiaotang      Wang; Tian      Wang; Xiaona      Song; Jiping      Gao; Guoqiang      Xu; Yunhui      Ma; Guohua      Song
doi:10.2174/0115680266280850231221074340
Abstract

The Hedgehog (Hh) signaling pathway plays a crucial role in diverse biological processes such as cell differentiation, proliferation, senescence, tumorigenesis, malignant transformation, and drug resistance. Aberrant Hh signaling, resulting from mutations and excessive activation, can contribute to the development of various diseases during different stages of biogenesis and development. Moreover, it has been linked to unfavorable outcomes in several human cancers, including basal cell carcinoma (BCC), multiple myeloma (MM), melanoma, and breast cancer. Hence, the presence of mutations and excessive activation of the Hh pathway presents obstacles and constraints in the realm of cancer treatment. Extant research has demonstrated that small molecule inhibitors are regarded as the most effective therapeutic approaches for targeting the Hh pathway in contrast to traditional chemotherapy and radiotherapy. Consequently, this review focuses on the present repertoire of small molecule inhibitors that target various components of the Hh pathway, including Hh ligands, Ptch receptors, Smo transmembrane proteins, and Gli nuclear transcription factors. This study provides a comprehensive analysis of small molecules' structural and functional aspects in the preclinical and clinical management of cancer. Additionally, it elucidates the obstacles encountered in targeting the Hh pathway for human cancer therapy and proposes potential therapeutic approaches.
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DOI https://dx.doi.org/10.2174/0115680266280850231221074340	Print ISSN 1568-0266
Publisher Name Bentham Science Publisher	Online ISSN 1873-4294
Current Topics in Medicinal Chemistry

Current Status of Hedgehog Signaling Inhibitors

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