Carboxylesterase Notum Is a Druggable Target to Modulate Wnt Signaling

Wnt signaling in cancer: therapeutic targeting of Wnt signaling beyond β-catenin and the destruction complex

(2020) Youn-Sang Jung et al.   EXPERIMENTAL AND MOLECULAR MEDICINE

Antiepileptic Drug Carbamazepine Binds to a Novel Pocket on the Wnt Receptor Frizzled-8

(2020) Yuguang Zhao et al.   JOURNAL OF MEDICINAL CHEMISTRY

Nature-derived compounds modulating Wnt/β-catenin pathway: a preventive and therapeutic opportunity in neoplastic diseases

(2020) G. Sferrazza et al.   Acta Pharmaceutica Sinica B

Wnts and the hallmarks of cancer

(2020) Zheng Zhong et al.   CANCER AND METASTASIS REVIEWS

Progenitors oppositely polarize WNT activators and inhibitors to orchestrate tissue development

(2020) Irina Matos et al.   eLife

Screening of a custom-designed acid fragment library identifies 1-phenylpyrroles and 1-phenylpyrrolidines as inhibitors of Notum carboxylesterase activity

(2020) William Mahy et al.   JOURNAL OF MEDICINAL CHEMISTRY

Single-Cell Profiling and SCOPE-Seq Reveal Lineage Dynamics of Adult Ventricular-Subventricular Zone Neurogenesis and NOTUM as a Key Regulator

(2020) Dogukan Mizrak et al.   Cell Reports

Caffeine inhibits Notum activity by binding at the catalytic pocket

(2020) Yuguang Zhao et al.   Communications Biology

A novel tankyrase inhibitor, MSC2504877, enhances the effects of clinical CDK4/6 inhibitors

(2019) Malini Menon et al.   Scientific Reports

Structure-guided design fine-tunes pharmacokinetics, tolerability, and antitumor profile of multispecific frizzled antibodies

(2019) Swetha Raman et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Modulating Wnt signaling at the root: Porcupine and Wnt acylation

(2019) Viviana I. Torres et al.   PHARMACOLOGY & THERAPEUTICS

Crystal structure of a mammalian Wnt–frizzled complex

(2019) Hidenori Hirai et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Osteoblast-derived NOTUM reduces cortical bone mass in mice and the NOTUM locus is associated with bone mineral density in humans

(2019) Sofia Movérare-Skrtic et al.   FASEB JOURNAL

Notum produced by Paneth cells attenuates regeneration of aged intestinal epithelium

(2019) Nalle Pentinmikko et al.   NATURE

Efficacy and safety from a phase 2B trial of SM04690, a novel, intra-articular, WNT pathway inhibitor for the treatment of osteoarthritis of the knee

(2019) Y. Yazici et al.   OSTEOARTHRITIS AND CARTILAGE

Modulation of the Wnt pathway through inhibition of CLK2 and DYRK1A by lorecivivint as a novel, potentially disease-modifying approach for knee osteoarthritis treatment

(2019) V. Deshmukh et al.   OSTEOARTHRITIS AND CARTILAGE

The CLK inhibitor SM08502 induces anti-tumor activity and reduces Wnt pathway gene expression in gastrointestinal cancer models

(2019) Betty Y. Tam et al.   CANCER LETTERS

An improved, scalable synthesis of Notum inhibitor LP-922056 using 1-chloro-1,2-benziodoxol-3-one as a superior electrophilic chlorinating agent

(2019) Nicky J Willis et al.   Beilstein Journal of Organic Chemistry

Scaffold-hopping identifies furano[2,3-d]pyrimidine amides as potent Notum inhibitors

(2019) Benjamin N. Atkinson et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Untangling human neurogenesis to understand and counteract brain disorders

(2019) Ruth Beckervordersandforth et al.   CURRENT OPINION IN PHARMACOLOGY

Structural characterization of melatonin as an inhibitor of the Wnt deacylase Notum

(2019) Yuguang Zhao et al.   JOURNAL OF PINEAL RESEARCH

Design and synthesis of gallocyanine inhibitors of DKK1/LRP6 interactions for treatment of Alzheimer’s disease

(2018) Savvas Thysiadis et al.   BIOORGANIC CHEMISTRY

From instruction to output: Wnt/PCP signaling in development and cancer

(2018) Ashley Ceinwen Humphries et al.   CURRENT OPINION IN CELL BIOLOGY

A small-molecule inhibitor of the Wnt pathway (SM04690) as a potential disease modifying agent for the treatment of osteoarthritis of the knee

(2018) V. Deshmukh et al.   OSTEOARTHRITIS AND CARTILAGE

Is β-Catenin a Druggable Target for Cancer Therapy?

(2018) Can Cui et al.   TRENDS IN BIOCHEMICAL SCIENCES

Mechanisms of Wnt signaling and control

(2018) Stephanie Grainger et al.   Wiley Interdisciplinary Reviews-Systems Biology and Medicine

Selective Irreversible Inhibitors of the Wnt-Deacylating Enzyme NOTUM Developed by Activity-Based Protein Profiling

(2018) Radu M. Suciu et al.   ACS Medicinal Chemistry Letters

Advanced Activity-Based Protein Profiling Application Strategies for Drug Development

(2018) Shan Wang et al.   Frontiers in Pharmacology

Abstract CT175: Biomarker analyses from a phase I study of WNT974, a first-in-class Porcupine inhibitor, in patients (pts) with advanced solid tumors

(2018) Jordi Rodon et al.   CANCER RESEARCH

Crystal structure of the Frizzled 4 receptor in a ligand-free state

(2018) Shifan Yang et al.   NATURE

Discovery of Potent Disheveled/Dvl Inhibitors Using Virtual Screening Optimized With NMR-Based Docking Performance Index

(2018) Kiminori Hori et al.   Frontiers in Pharmacology

Adult Hippocampal Neurogenesis: A Coming-of-Age Story

(2018) H. Georg Kuhn et al.   JOURNAL OF NEUROSCIENCE

Crystal structure of a membrane-bound O-acyltransferase

(2018) Dan Ma et al.   NATURE

Wnt is back in drugmakers' sights, but is it druggable?

(2018) Cormac Sheridan   NATURE BIOTECHNOLOGY

712 A small molecule modulator of the wnt pathway (SM04554) as a potential topical treatment for androgenetic alopecia (AGA)

(2017) V. Deshmukh et al.   JOURNAL OF INVESTIGATIVE DERMATOLOGY

Inhibition of β-Catenin Signaling in the Skin Rescues Cutaneous Adipogenesis in Systemic Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Trial of C-82

(2017) Robert Lafyatis et al.   JOURNAL OF INVESTIGATIVE DERMATOLOGY

Discovery of novel frizzled-7 inhibitors by targeting the receptor’s transmembrane domain

(2017) Wei Zhang et al.   Oncotarget

Stimulation of cortical bone formation with thienopyrimidine based inhibitors of Notum Pectinacetylesterase

(2016) James E. Tarver et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

4H-Thieno[3,2-c]chromene based inhibitors of Notum Pectinacetylesterase

(2016) Qiang Han et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Reversal of Synapse Degeneration by Restoring Wnt Signaling in the Adult Hippocampus

(2016) Aude Marzo et al.   CURRENT BIOLOGY

Generating Cellular Diversity and Spatial Form: Wnt Signaling and the Evolution of Multicellular Animals

(2016) Kyle M. Loh et al.   DEVELOPMENTAL CELL

Synthesis and evaluation of gallocyanine dyes as potential agents for the treatment of Alzheimer's disease and related neurodegenerative tauopathies

(2016) Spyros Mpousis et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Fatty acylation of Wnt proteins

(2016) Aaron H Nile et al.   Nature Chemical Biology

Wnt signaling in cancer

(2016) T Zhan et al.   ONCOGENE

Dentin Dysplasia in Notum Knockout Mice

(2016) P. Vogel et al.   VETERINARY PATHOLOGY

NOTUM is a potential pharmacodynamic biomarker of Wnt pathway inhibition

(2016) Babita Madan et al.   Oncotarget

Wnt Drug Discovery: Weaving Through the Screens, Patents and Clinical Trials

(2016) Benjamin Lu et al.   Cancers

Wnt5a Signaling in Cancer

(2016) Marwa Asem et al.   Cancers

Generation of Mice with Hepatocyte-Specific Conditional Deletion of Notum

(2016) Frédéric Canal et al.   PLoS One

The use of porcupine inhibitors to target Wnt-driven cancers

(2015) Soo Yei Ho et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Small-molecule inhibitors of Wnt signaling pathway: towards novel anticancer therapeutics

(2015) Shilong Zheng et al.   Future Medicinal Chemistry

Structure-based Discovery of Novel Small Molecule Wnt Signaling Inhibitors by Targeting the Cysteine-rich Domain of Frizzled

(2015) Ho-Jin Lee et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Abstract C45: Phase I study of WNT974, a first-in-class Porcupine inhibitor, in advanced solid tumors

(2015) Filip Janku et al.   MOLECULAR CANCER THERAPEUTICS

Notum deacylates Wnt proteins to suppress signalling activity

(2015) Satoshi Kakugawa et al.   NATURE

Roles of Wnt Signaling in the Neurogenic Niche of the Adult Mouse Ventricular–Subventricular Zone

(2015) Yuki Hirota et al.   NEUROCHEMICAL RESEARCH

Novel insights into Notum and glypicans regulation in colorectal cancer

(2015) Mariangela De Robertis et al.   Oncotarget

Inhibition of Cyclic Adenosine Monophosphate (cAMP)-response Element-binding Protein (CREB)-binding Protein (CBP)/β-Catenin Reduces Liver Fibrosis in Mice

(2015) Yosuke Osawa et al.   EBioMedicine

Abstract 1907: Wnt pathway antagonist OMP-54F28 (FZD8-Fc) inhibits tumor growth and reduces tumor-initiating cell frequency in patient-derived hepatocellular carcinoma and ovarian cancer xenograft models

(2015) Pete Yeung et al.   CANCER RESEARCH

Identification of Key Residues and Regions Important for Porcupine-mediated Wnt Acylation

(2014) Jessica Rios-Esteves et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Can we safely target the WNT pathway?

(2014) Michael Kahn   NATURE REVIEWS DRUG DISCOVERY

An integral program for tissue renewal and regeneration: Wnt signaling and stem cell control

(2014) H. Clevers et al.   SCIENCE

A Novel Tankyrase Small-Molecule Inhibitor Suppresses APC Mutation-Driven Colorectal Tumor Growth

(2013) T. Lau et al.   CANCER RESEARCH

Identification of NVP-TNKS656: The Use of Structure–Efficiency Relationships To Generate a Highly Potent, Selective, and Orally Active Tankyrase Inhibitor

(2013) Michael D. Shultz et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structural Basis and SAR for G007-LK, a Lead Stage 1,2,4-Triazole Based Specific Tankyrase 1/2 Inhibitor

(2013) Andrew Voronkov et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure of the human smoothened receptor bound to an antitumour agent

(2013) Chong Wang et al.   NATURE

Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974

(2013) J. Liu et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Wnt Stabilization of  -Catenin Reveals Principles for Morphogen Receptor-Scaffold Assemblies

(2013) S.-E. Kim et al.   SCIENCE

The Role of Ryk and Ror Receptor Tyrosine Kinases in Wnt Signal Transduction

(2013) J. Green et al.   Cold Spring Harbor Perspectives in Biology

Drugging the undruggable: Transcription therapy for cancer

(2012) Chunhong Yan et al.   BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER

Wnt/β-Catenin Signaling and Disease

(2012) Hans Clevers et al.   CELL

Roles of N-glycosylation and lipidation in Wg secretion and signaling

(2012) Xiaofang Tang et al.   DEVELOPMENTAL BIOLOGY

The pharmacological landscape and therapeutic potential of serine hydrolases

(2012) Daniel A. Bachovchin et al.   NATURE REVIEWS DRUG DISCOVERY

Wnt pathway inhibition via the targeting of Frizzled receptors results in decreased growth and tumorigenicity of human tumors

(2012) A. Gurney et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Structural Basis of Wnt Recognition by Frizzled

(2012) C. Y. Janda et al.   SCIENCE

Secreted and Transmembrane Wnt Inhibitors and Activators

(2012) C.-M. Cruciat et al.   Cold Spring Harbor Perspectives in Biology

Crystal structures of the extracellular domain of LRP6 and its complex with DKK1

(2011) Zhihong Cheng et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Structural Basis for the Interaction between Tankyrase-2 and a Potent Wnt-Signaling Inhibitor

(2010) Tobias Karlberg et al.   JOURNAL OF MEDICINAL CHEMISTRY

Modulation of Wnt signaling through inhibition of secreted frizzled-related protein I (sFRP-1) with N-substituted piperidinyl diphenylsulfonyl sulfonamides: Part II

(2009) William J. Moore et al.   BIOORGANIC & MEDICINAL CHEMISTRY

A small molecule inhibitor of the Wnt antagonist secreted frizzled-related protein-1 stimulates bone formation

(2009) Peter V.N. Bodine et al.   BONE

Wnt/β-Catenin Signaling: Components, Mechanisms, and Diseases

(2009) Bryan T. MacDonald et al.   DEVELOPMENTAL CELL

Discovery and Characterization of a Small Molecule Inhibitor of the PDZ Domain of Dishevelled

(2009) David Grandy et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

(1-(4-(Naphthalen-2-yl)pyrimidin-2-yl)piperidin-4-yl)methanamine: A Wingless β-Catenin Agonist That Increases Bone Formation Rate

(2009) Jeffrey C. Pelletier et al.   JOURNAL OF MEDICINAL CHEMISTRY

Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling

(2009) Shih-Min A. Huang et al.   NATURE

Inhibition of Wnt signaling by Dishevelled PDZ peptides

(2009) Yingnan Zhang et al.   Nature Chemical Biology

Small molecule–mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer

(2009) Baozhi Chen et al.   Nature Chemical Biology

Wingless Promotes Proliferative Growth in a Gradient-Independent Manner

(2009) L. A. Baena-Lopez et al.   Science Signaling

Human homolog of NOTUM, overexpressed in hepatocellular carcinoma, is regulated transcriptionally by β-catenin/TCF

(2008) Yuichi Torisu et al.   CANCER SCIENCE

Activation of Wingless Targets Requires Bipartite Recognition of DNA by TCF

(2008) Mikyung V. Chang et al.   CURRENT BIOLOGY

Modulation of Wnt Signaling Through Inhibition of Secreted Frizzled-Related Protein I (sFRP-1) with N-Substituted Piperidinyl Diphenylsulfonyl Sulfonamides†

(2008) William J. Moore et al.   JOURNAL OF MEDICINAL CHEMISTRY