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Clinical Experience With Hedgehog Pathway Inhibitors
Journal of Clinical Oncology, 2010The Hedgehog (Hh) signaling pathway is critical for cell growth and differentiation during embryogenesis and early development. While it is mostly quiescent in adults, inappropriate reactivation of the Hh pathway has been shown to be involved in the development of cancer.
Jennifer A, Low, Frederic J, de Sauvage
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GDC-0449—A Potent Inhibitor of the Hedgehog Pathway
Bioorganic and Medicinal Chemistry Letters, 2009SAR for a wide variety of heterocyclic replacements for a benzimidazole led to the discovery of functionalized 2-pyridyl amides as novel inhibitors of the hedgehog pathway. The 2-pyridyl amides were optimized for potency, PK, and drug-like properties by modifications to the amide portion of the molecule resulting in 31 (GDC-0449).
Lee L. Rubin +2 more
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Current Status of Hedgehog Signaling Inhibitors
Current Topics in Medicinal ChemistryAbstract: The Hedgehog (Hh) signaling pathway plays a crucial role in diverse biological pro-cesses such as cell differentiation, proliferation, senescence, tumorigenesis, malignant transfor-mation, and drug resistance. Aberrant Hh signaling, resulting from mutations and excessive acti-vation, can contribute to the development of various diseases ...
Xiaotang, Wang +6 more
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A novel hedgehog inhibitor for the treatment of hematological malignancies
Anti-Cancer Drugs, 2018The hedgehog-smoothened (HH/SMO) pathway has been proposed as a potential therapeutic target for hematological malignancies. Our previous studies designed a series of HH inhibitors with novel scaffolds distinctive from vismodegib, the first Food and Drug Administration-approved HH inhibitor for the treatment of basal-cell carcinoma and medulloblastoma.
Peng, Lin +9 more
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Hedgehog pathway and smoothened inhibitors in cancer therapies
Anti-Cancer Drugs, 2018The hedgehog (Hh) pathway plays an important role in cancer development and maintenance, as ~25% of all cancers have aberrant Hh pathway activation. Targeted therapy for inhibition of the Hh pathway was thought to be promising for achieving clinical response in the Hh-dependent cancers.
Kirti K, Chahal +2 more
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Drug Resistance Updates, 2012
Hedgehog (Hh) signaling is a principal component of the morphogenetic code best known to direct pattern formation during embryogenesis. The Hh pathway remains active in adulthood however where it guides tissue regeneration and remodeling and Hh production in the niche plays an important role in maintaining stem cell compartment size.
Souza Queiroz, Karla +2 more
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Hedgehog (Hh) signaling is a principal component of the morphogenetic code best known to direct pattern formation during embryogenesis. The Hh pathway remains active in adulthood however where it guides tissue regeneration and remodeling and Hh production in the niche plays an important role in maintaining stem cell compartment size.
Souza Queiroz, Karla +2 more
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Hedgehog inhibitors: a patent review (2013 – present)
Expert Opinion on Therapeutic Patents, 2015The hedgehog (Hh) signaling pathway is an important signaling pathway, playing a critical role in regulation of cell growth, development, metastasis and angiogenesis. Aberrant activation of this pathway has been linked to the development of several human tumor types, which makes it an attractive target for cancer treatment.
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