Results 191 to 200 of about 28,708 (231)

GDC-0449—A potent inhibitor of the hedgehog pathway

Bioorganic & Medicinal Chemistry Letters, 2009
SAR 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).
Kirk D, Robarge, Shirley A, Brunton, Georgette M, Castanedo, Yong, Cui, Michael S, Dina, Richard, Goldsmith, Stephen E, Gould, Oivin, Guichert, Janet L, Gunzner, Jason, Halladay, Wei, Jia, Cyrus, Khojasteh, Michael F T, Koehler, Karen, Kotkow, Hank, La, Rebecca L, Lalonde, Kevin, Lau, Leslie, Lee, Derek, Marshall, James C, Marsters, Lesley J, Murray, Changgeng, Qian, Lee L, Rubin, Laurent, Salphati, Mark S, Stanley, John H A, Stibbard, Daniel P, Sutherlin, Savita, Ubhayaker, Shumei, Wang, Susan, Wong, Minli, Xie   +30 more
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Hedgehog pathway and smoothened inhibitors in cancer therapies

Anti-Cancer Drugs, 2018
The 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, Milind, Parle, Ruben, Abagyan   +2 more
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Synthesis and Evaluation of Aminothiazole Derivatives as Hedgehog Pathway Inhibitors

Chemistry & Biodiversity, 2019
AbstractA series of aminothiazole derivatives bearing the benzimidazole moiety were synthesized and evaluated in Gli luciferase reporter assays. Lead optimization led to the discovery of potent hedgehog pathway antagonist 18 (2‐[3‐(1H‐benzimidazol‐2‐yl)‐4‐chloroanilino]‐N‐[4‐(trifluoromethyl)phenyl]‐1,3‐thiazole‐4‐carboxamide), with IC50 values in ...
Chiyu Sun, Ying Zhang, Lin Lin, Shuyuan Liu, Rui Wang, Wei Zang, Weijia Meng, Xiaofeng Chen   +7 more
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Small-Molecule Inhibitors of the Hedgehog Pathway

2011
The causal link between uncontrolled Hedgehog (Hh) pathway activation and oncogenesis has inspired the development of small-molecule inhibitors of this developmental signaling pathway. In this chapter, we discuss how a cyclopia-inducing natural product isolated in the 1950s has engendered a pharmacopoeia of compounds that block Hh target gene ...
Ari J. Firestone, James K. Chen
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Recent patents for Hedgehog pathway inhibitors for the treatment of malignancy

Expert Opinion on Therapeutic Patents, 2009
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 ...
Martin R, Tremblay, Michael, Nesler, Robin, Weatherhead, Alfredo C, Castro   +3 more
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Targeting Hedgehog signaling and understanding refractory response to treatment with Hedgehog pathway inhibitors

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, Spek, CA, Peppelenbosch, Maikel   +2 more
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Hedgehog pathway inhibitors in eyelid tumors

Acta Ophthalmologica
Aims/Purpose: Basal cell carcinoma (BCC) is the most common type of tumor worldwide. Although it has a low capacity for systemic spread, it exhibits a high rate of local invasion. The most frequently affected areas are the face and neck. So far, the most widely used treatment has been surgery in its various forms: excision‐electrodesiccation‐curettage,
Elisa Funes, Jacobo Yañez Merino, Maria Sopeña‐Pinilla, Olga Ciobotaru, Ana Pueyo Bestué, Ignacio Pueyo‐Bestué, Diego Fernandez‐Velasco, Victor Mallen, Javier Bermudez, Andrés Biescas   +9 more
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Oral Hedgehog-Pathway Inhibitors for Basal-Cell Carcinoma

New England Journal of Medicine, 2012
Basal-cell carcinoma of the skin is the most common cancer worldwide, and its prevalence is increasing, accounting for 80% of nonmelanoma skin cancers.1 In 2006, more than 2.1 million new cases of nonmelanoma skin cancer were treated in the United States.2 Basal-cell carcinoma has many clinical subtypes and can progress to an advanced state in which ...
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Hedgehog pathway inhibitors: a patent review (2009 – present)

Expert Opinion on Therapeutic Patents, 2013
The hedgehog (Hh) pathway is a developmental signaling pathway that plays a key role in directing cellular growth and tissue patterning during embryonic development. Dysregulation of Hh signaling has been linked to the development of a variety of human tumors, and numerous drug development programs in both academia and industry are actively exploring ...
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Evaluation of vitamin D3 A-ring analogues as Hedgehog pathway inhibitors

Bioorganic & Medicinal Chemistry Letters, 2012
A structure-activity relationship study focusing on the A-ring of vitamin D3 (VD3) was undertaken to elucidate its role in inhibiting the Hedgehog pathway and in mediating anti-cancer effects. Analogues resulting from simple functional group substitution at 3' position of VD3 were evaluated in a variety of biological assays to determine their ability ...
Upasana, Banerjee, Manuka, Ghosh, M, Kyle Hadden   +2 more
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