Recent advances in the design of Hedgehog pathway inhibitors for the treatment of malignancies

Design, synthesis, and evaluation of pyrrolo[2,1-f][1,2,4]triazine derivatives as novel hedgehog signaling pathway inhibitors

(2014) Minhang Xin et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Open-Label, Exploratory Phase II Trial of Oral Itraconazole for the Treatment of Basal Cell Carcinoma

(2014) Daniel J. Kim et al.   JOURNAL OF CLINICAL ONCOLOGY

Target identification for a Hedgehog pathway inhibitor reveals the receptor GPR39

(2014) Frederic Bassilana et al.   Nature Chemical Biology

Lipidic cubic phase injector facilitates membrane protein serial femtosecond crystallography

(2014) Uwe Weierstall et al.   Nature Communications

Cyclopamine analogs bearing exocyclic methylenes are highly potent and acid-stable inhibitors of hedgehog signaling

(2013) Johann Moschner et al.   Beilstein Journal of Organic Chemistry

The discovery of novel N-(2-pyrimidinylamino) benzamide derivatives as potent hedgehog signaling pathway inhibitors

(2013) Minhang Xin et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Synthesis and evaluation of 4-(2-pyrimidinylamino) benzamides inhibitors of hedgehog signaling pathway

(2013) Minhang Xin et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Itraconazole and Arsenic Trioxide Inhibit Hedgehog Pathway Activation and Tumor Growth Associated with Acquired Resistance to Smoothened Antagonists

(2013) James Kim et al.   CANCER CELL

Targeting Sonic Hedgehog-Associated Medulloblastoma through Inhibition of Aurora and Polo-like Kinases

(2013) S. L. Markant et al.   CANCER RESEARCH

Hedgehog Pathway Agonism: Therapeutic Potential and Small-Molecule Development

(2013) M. Kyle Hadden   ChemMedChem

Discovery of NVP-LEQ506, a Second-Generation Inhibitor of Smoothened

(2013) Stefan Peukert et al.   ChemMedChem

Hedgehog Pathway Modulation by Multiple Lipid Binding Sites on the Smoothened Effector of Signal Response

(2013) Benjamin R. Myers et al.   DEVELOPMENTAL CELL

Inhibition mechanism exploration of investigational drug TAK-441 as inhibitor against Vismodegib-resistant Smoothened mutant

(2013) Tsuyoshi Ishii et al.   EUROPEAN JOURNAL OF PHARMACOLOGY

TAK-441, a novel investigational smoothened antagonist, delays castration-resistant progression in prostate cancer by disrupting paracrine hedgehog signaling

(2013) Naokazu Ibuki et al.   INTERNATIONAL JOURNAL OF CANCER

Nonclassical Activation of Hedgehog Signaling Enhances Multidrug Resistance and Makes Cancer Cells Refractory to Smoothened-targeting Hedgehog Inhibition

(2013) Shamik Das et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Discovery of Small-Molecule Modulators of the Sonic Hedgehog Pathway

(2013) Giannina I. Schaefer et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Novel Neutralizing Hedgehog Antibody MEDI-5304 Exhibits Antitumor Activity by Inhibiting Paracrine Hedgehog Signaling

(2013) N. R. Michaud et al.   MOLECULAR CANCER THERAPEUTICS

Structure of the human smoothened receptor bound to an antitumour agent

(2013) Chong Wang et al.   NATURE

Inhibitors of Hedgehog acyltransferase block Sonic Hedgehog signaling

(2013) Elissaveta Petrova et al.   Nature Chemical Biology

Oxysterol binding to the extracellular domain of Smoothened in Hedgehog signaling

(2013) Daniel Nedelcu et al.   Nature Chemical Biology

Unraveling the therapeutic potential of the Hedgehog pathway in cancer

(2013) Dereck Amakye et al.   NATURE MEDICINE

The mechanisms of Hedgehog signalling and its roles in development and disease

(2013) James Briscoe et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Targeting Gli transcription activation by small molecule suppresses tumor growth

(2013) G Bosco-Clément et al.   ONCOGENE

Molecular Dynamics Simulations of Sonic Hedgehog-Receptor and Inhibitor Complexes and Their Applications for Potential Anticancer Agent Discovery

(2013) Swan Hwang et al.   PLoS One

Identification of Vitamin D3-Based Hedgehog Pathway Inhibitors That Incorporate an Aromatic A-Ring Isostere

(2013) Albert M. DeBerardinis et al.   ACS Medicinal Chemistry Letters

Structural insights into the role of the Smoothened cysteine-rich domain in Hedgehog signalling

(2013) Rajashree Rana et al.   Nature Communications

Structure and function of the Smoothened extracellular domain in vertebrate Hedgehog signaling

(2013) Sigrid Nachtergaele et al.   eLife

Selective Identification of Hedgehog Pathway Antagonists By Direct Analysis of Smoothened Ciliary Translocation

(2012) Yu Wang et al.   ACS Chemical Biology

Initial Assessment of Tumor Regrowth After Vismodegib in Advanced Basal Cell Carcinoma

(2012) Anne Lynn S. Chang et al.   ARCHIVES OF DERMATOLOGY

Control of stem cells and cancer stem cells by Hedgehog signaling: Pharmacologic clues from pathway dissection

(2012) Sonia Coni et al.   BIOCHEMICAL PHARMACOLOGY

Discovery of pyrrolo[3,2-c]quinoline-4-one derivatives as novel hedgehog signaling inhibitors

(2012) Tomohiro Ohashi et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Discovery of the investigational drug TAK-441, a pyrrolo[3,2-c]pyridine derivative, as a highly potent and orally active hedgehog signaling inhibitor: Modification of the core skeleton for improved solubility

(2012) Tomohiro Ohashi et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Probing the structural requirements for vitamin D3 inhibition of the hedgehog signaling pathway

(2012) Albert M. DeBerardinis et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

The Crosstalk of mTOR/S6K1 and Hedgehog Pathways

(2012) Yan Wang et al.   CANCER CELL

Cancer Stem Cells: Impact, Heterogeneity, and Uncertainty

(2012) Jeffrey A. Magee et al.   CANCER CELL

Abstract 2819: Identification and characterization of a novel smoothened antagonist for the treatment of cancer with deregulated hedgehog signaling

(2012) Mark H. Bender et al.   CANCER RESEARCH

Hedgehog and Notch Signaling Regulate Self-Renewal of Undifferentiated Pleomorphic Sarcomas

(2012) C. Y. Y. Wang et al.   CANCER RESEARCH

Glucocorticoid Compounds Modify Smoothened Localization and Hedgehog Pathway Activity

(2012) Yu Wang et al.   CHEMISTRY & BIOLOGY

Vismodegib

(2012) C. M. Rudin   CLINICAL CANCER RESEARCH

Tumor-stroma interaction in orthotopic primary pancreatic cancer xenografts during hedgehog pathway inhibition

(2012) Qing Chang et al.   INTERNATIONAL JOURNAL OF CANCER

Acylthiourea, Acylurea, and Acylguanidine Derivatives with Potent Hedgehog Inhibiting Activity

(2012) Antonio Solinas et al.   JOURNAL OF MEDICINAL CHEMISTRY

Efficacy and Safety of Vismodegib in Advanced Basal-Cell Carcinoma

(2012) Aleksandar Sekulic et al.   NEW ENGLAND JOURNAL OF MEDICINE

Hedgehog pathway inhibitor saridegib (IPI-926) increases lifespan in a mouse medulloblastoma model

(2012) M. J. Lee et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Small molecule inhibitors of Smoothened ciliary localization and ciliogenesis

(2012) V. M. Wu et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Macrocyclic Hedgehog Pathway Inhibitors: Optimization of Cellular Activity and Mode of Action Studies

(2012) Chris Dockendorff et al.   ACS Medicinal Chemistry Letters

Identification of MK-5710 ((8aS)-8a-methyl-1,3-dioxo-2-[(1S,2R)-2-phenylcyclopropyl]-N-(1-phenyl-1H-pyrazol-5-yl)hexahydroimid azo[1,5-a]pyrazine-7(1H)-carboxamide), a potent smoothened antagonist for use in Hedgehog pathway dependent malignancies, Part 1

(2011) Savina Malancona et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Identification of MK-5710 ((8aS)-8a-methyl-1,3-dioxo-2-[(1S,2R)-2-phenylcyclo- propyl]-N-(1-phenyl-1H-pyrazol-5-yl)hexahydro-imidazo[1,5-a]pyrazine-7(1H)-carboxamide), a potent smoothened antagonist for use in Hedgehog pathway dependent malignancies, Part 2

(2011) Olaf Kinzel et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Identification of a series of 4-[3-(quinolin-2-yl)-1,2,4-oxadiazol-5-yl]piperazinyl ureas as potent smoothened antagonist hedgehog pathway inhibitors

(2011) Jesus M. Ontoria et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

N-(2-alkylaminoethyl)-4-(1,2,4-oxadiazol-5-yl)piperazine-1-carboxamides as highly potent smoothened antagonists

(2011) Ester Muraglia et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Evaluation of vitamin D3 A-ring analogues as Hedgehog pathway inhibitors

(2011) Upasana Banerjee et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Vitamin D3 Inhibits Hedgehog Signaling and Proliferation in Murine Basal Cell Carcinomas

(2011) J. Y. Tang et al.   Cancer Prevention Research

Itraconazole Inhibits Angiogenesis and Tumor Growth in Non-Small Cell Lung Cancer

(2011) B. T. Aftab et al.   CANCER RESEARCH

Hedgehog Fights Back: Mechanisms of Acquired Resistance against Smoothened Antagonists

(2011) C. Metcalfe et al.   CANCER RESEARCH

Exo-Cyclopamine—a stable and potent inhibitor of hedgehog-signaling

(2011) Philipp Heretsch et al.   CHEMICAL COMMUNICATIONS

Small Molecule Antagonists in Distinct Binding Modes Inhibit Drug-Resistant Mutant of Smoothened

(2011) Haiyan Tao et al.   CHEMISTRY & BIOLOGY

Polymeric Nanoparticle-Encapsulated Hedgehog Pathway Inhibitor HPI-1 (NanoHHI) Inhibits Systemic Metastases in an Orthotopic Model of Human Hepatocellular Carcinoma

(2011) Yang Xu et al.   CLINICAL CANCER RESEARCH

Mechanisms of Hedgehog signalling in cancer

(2011) Kieren D. Marini et al.   GROWTH FACTORS

Itraconazole Side Chain Analogues: Structure–Activity Relationship Studies for Inhibition of Endothelial Cell Proliferation, Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) Glycosylation, and Hedgehog Signaling

(2011) Wei Shi et al.   JOURNAL OF MEDICINAL CHEMISTRY

Effective Targeting of Hedgehog Signaling in a Medulloblastoma Model with PF-5274857, a Potent and Selective Smoothened Antagonist That Penetrates the Blood-Brain Barrier

(2011) A. Rohner et al.   MOLECULAR CANCER THERAPEUTICS

A Polymeric Nanoparticle Encapsulated Small-Molecule Inhibitor of Hedgehog Signaling (NanoHHI) Bypasses Secondary Mutational Resistance to Smoothened Antagonists

(2011) V. Chenna et al.   MOLECULAR CANCER THERAPEUTICS

The cancer stem cell: premises, promises and challenges

(2011) Hans Clevers   NATURE MEDICINE

A Novel Synthetic Smoothened Antagonist Transiently Inhibits Pancreatic Adenocarcinoma Xenografts in a Mouse Model

(2011) Martin F. Strand et al.   PLoS One

Design, synthesis, and biological evaluation of estrone-derived hedgehog signaling inhibitors

(2011) Jeffrey D. Winkler et al.   TETRAHEDRON

Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened

(2011) Michael J. Munchhof et al.   ACS Medicinal Chemistry Letters

DISCOVERY AND EVALUATION OF POTENTIAL SONIC HEDGEHOG SIGNALING PATHWAY INHIBITORS USING PHARMACOPHORE MODELING AND MOLECULAR DYNAMICS SIMULATIONS

(2011) SWAN HWANG et al.   Journal of Bioinformatics and Computational Biology

Cyclopamine and Hedgehog Signaling: Chemistry, Biology, Medical Perspectives

(2010) Philipp Heretsch et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Assessing the efficacy of the Hedgehog pathway inhibitor vitamin D3 in a murine xenograft model for pancreatic cancer

(2010) Lois W. Brüggemann et al.   CANCER BIOLOGY & THERAPY

Itraconazole, a Commonly Used Antifungal that Inhibits Hedgehog Pathway Activity and Cancer Growth

(2010) James Kim et al.   CANCER CELL

Small Molecule Inhibition of GDC-0449 Refractory Smoothened Mutants and Downstream Mechanisms of Drug Resistance

(2010) Gerrit J. P. Dijkgraaf et al.   CANCER RESEARCH

Targeting Hedgehog -- a Cancer Stem Cell Pathway

(2010) A. A. Merchant et al.   CLINICAL CANCER RESEARCH

Hedgehog Pathway Antagonist 5E1 Binds Hedgehog at the Pseudo-active Site

(2010) Henry R. Maun et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Arsenic trioxide inhibits human cancer cell growth and tumor development in mice by blocking Hedgehog/GLI pathway

(2010) Elspeth M. Beauchamp et al.   JOURNAL OF CLINICAL INVESTIGATION

Molecular Therapy Targeting Sonic Hedgehog and Hepatocyte Growth Factor Signaling in a Mouse Model of Medulloblastoma

(2010) V. Coon et al.   MOLECULAR CANCER THERAPEUTICS

Virtual Screening-Based Discovery and Mechanistic Characterization of the Acylthiourea MRT-10 Family as Smoothened Antagonists

(2010) F. Manetti et al.   MOLECULAR PHARMACOLOGY

Activation of the hedgehog pathway confers a poor prognosis in embryonal and fusion gene-negative alveolar rhabdomyosarcoma

(2010) A Zibat et al.   ONCOGENE

Arsenic antagonizes the Hedgehog pathway by preventing ciliary accumulation and reducing stability of the Gli2 transcriptional effector

(2010) J. Kim et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Interfering with Resistance to Smoothened Antagonists by Inhibition of the PI3K Pathway in Medulloblastoma

(2010) S. Buonamici et al.   Science Translational Medicine

Discovery of NVP-LDE225, a Potent and Selective Smoothened Antagonist

(2010) Shifeng Pan et al.   ACS Medicinal Chemistry Letters

GDC-0449—A potent inhibitor of the hedgehog pathway

(2009) Kirk D. Robarge et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Structure−Activity Relationships and Cancer-Cell Selective Toxicity of Novel Inhibitors of Glioma-Associated Oncogene Homologue 1 (Gli1) Mediated Transcription

(2009) Neeraj Mahindroo et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of a Potent and Orally Active Hedgehog Pathway Antagonist (IPI-926)

(2009) Martin R. Tremblay et al.   JOURNAL OF MEDICINAL CHEMISTRY

1-Amino-4-benzylphthalazines as Orally Bioavailable Smoothened Antagonists with Antitumor Activity

(2009) Karen Miller-Moslin et al.   JOURNAL OF MEDICINAL CHEMISTRY

Evidence for Allosteric Interactions of Antagonist Binding to the Smoothened Receptor

(2009) C. M. Rominger et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

A small molecule that binds Hedgehog and blocks its signaling in human cells

(2009) Benjamin Z Stanton et al.   Nature Chemical Biology

Treatment of Medulloblastoma with Hedgehog Pathway Inhibitor GDC-0449

(2009) Charles M. Rudin et al.   NEW ENGLAND JOURNAL OF MEDICINE

Activation of the hedgehog-signaling pathway in human cancer and the clinical implications

(2009) L Yang et al.   ONCOGENE

Sonic hedgehog paracrine signaling regulates metastasis and lymphangiogenesis in pancreatic cancer

(2009) J M Bailey et al.   ONCOGENE

Design and Synthesis of Inhibitors of Hedgehog Signaling Based on the Alkaloid Cyclopamine

(2009) Jeffrey D. Winkler et al.   ORGANIC LETTERS

Small-molecule inhibitors reveal multiple strategies for Hedgehog pathway blockade

(2009) J. M. Hyman et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Hedgehog signaling is restricted to the stromal compartment during pancreatic carcinogenesis

(2009) H. Tian et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Smoothened Mutation Confers Resistance to a Hedgehog Pathway Inhibitor in Medulloblastoma

(2009) R. L. Yauch et al.   SCIENCE

Synthesis and anticancer activity studies of cyclopamine derivatives

(2008) Jianjun Zhang et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Hedgehog Signaling in Development and Cancer

(2008) Jin Jiang et al.   DEVELOPMENTAL CELL

Hedgehog-Induced Survival of B-Cell Chronic Lymphocytic Leukemia Cells in a Stromal Cell Microenvironment: A Potential New Therapeutic Target

(2008) G. V. Hegde et al.   MOLECULAR CANCER RESEARCH

An orally bioavailable small-molecule inhibitor of Hedgehog signaling inhibits tumor initiation and metastasis in pancreatic cancer

(2008) G. Feldmann et al.   MOLECULAR CANCER THERAPEUTICS

A paracrine requirement for hedgehog signalling in cancer

(2008) Robert L. Yauch et al.   NATURE