A selective WDR5 degrader inhibits acute myeloid leukemia in patient-derived mouse models

Discovery of Potent and Selective Epidermal Growth Factor Receptor (EGFR) Bifunctional Small-Molecule Degraders

(2020) Meng Cheng et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of WD Repeat-Containing Protein 5 (WDR5)–MYC Inhibitors Using Fragment-Based Methods and Structure-Based Design

(2020) Selena Chacón Simon et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structural Insights into PROTAC-Mediated Degradation of Bcl-xL

(2020) Chun-wa Chung et al.   ACS Chemical Biology

Snapshots and ensembles of BTK and cIAP1 protein degrader ternary complexes

(2020) James Schiemer et al.   Nature Chemical Biology

Discovery of ARD-69 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Androgen Receptor (AR) for the Treatment of Prostate Cancer

(2019) Xin Han et al.   JOURNAL OF MEDICINAL CHEMISTRY

Displacement of WDR5 from Chromatin by a WIN Site Inhibitor with Picomolar Affinity

(2019) Erin R. Aho et al.   Cell Reports

BAF complex vulnerabilities in cancer demonstrated via structure-based PROTAC design

(2019) William Farnaby et al.   Nature Chemical Biology

PHF19 promotes multiple myeloma tumorigenicity through PRC2 activation and broad H3K27me3 domain formation

(2019) Zhihong Ren et al.   BLOOD

Targeted protein degradation: expanding the toolbox

(2019) Matthieu Schapira et al.   NATURE REVIEWS DRUG DISCOVERY

Interaction of the oncoprotein transcription factor MYC with its chromatin cofactor WDR5 is essential for tumor maintenance

(2019) Lance R. Thomas et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Structure-Based Design of a Macrocyclic PROTAC

(2019) Andrea Testa et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Discovery and Optimization of Salicylic Acid-Derived Sulfonamide Inhibitors of the WD Repeat-Containing Protein 5–MYC Protein–Protein Interaction

(2019) Jonathan D. Macdonald et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery and Structure-Based Optimization of Potent and Selective WD Repeat Domain 5 (WDR5) Inhibitors Containing a Dihydroisoquinolinone Bicyclic Core

(2019) Jianhua Tian et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of Potent 2-Aryl-6,7-dihydro-5H-pyrrolo[1,2-a]imidazoles as WDR5-WIN-Site Inhibitors Using Fragment-Based Methods and Structure-Based Design

(2018) Feng Wang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Overexpression of WD repeat domain 5 associates with aggressive clinicopathological features and unfavorable prognosis in head neck squamous cell carcinoma

(2018) Yaping Wu et al.   JOURNAL OF ORAL PATHOLOGY & MEDICINE

3-Fluoro-4-hydroxyprolines: Synthesis, Conformational Analysis, and Stereoselective Recognition by the VHL E3 Ubiquitin Ligase for Targeted Protein Degradation

(2018) Andrea Testa et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Plasticity in binding confers selectivity in ligand-induced protein degradation

(2018) Radosław P. Nowak et al.   Nature Chemical Biology

Moonlighting with WDR5: A Cellular Multitasker

(2018) Alissa Guarnaccia et al.   Journal of Clinical Medicine

ZFX Mediates Non-canonical Oncogenic Functions of the Androgen Receptor Splice Variant 7 in Castrate-Resistant Prostate Cancer

(2018) Ling Cai et al.   MOLECULAR CELL

Up-regulated WDR5 promotes gastric cancer formation by induced cyclin D1 expression

(2017) Wei Sun et al.   JOURNAL OF CELLULAR BIOCHEMISTRY

Discovery of a Highly Potent, Cell-Permeable Macrocyclic Peptidomimetic (MM-589) Targeting the WD Repeat Domain 5 Protein (WDR5)–Mixed Lineage Leukemia (MLL) Protein–Protein Interaction

(2017) Hacer Karatas et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structural basis of PROTAC cooperative recognition for selective protein degradation

(2017) Morgan S Gadd et al.   Nature Chemical Biology

Integrating macromolecular X-ray diffraction data with the graphical user interface iMosflm

(2017) Harold R Powell et al.   Nature Protocols

WD40 repeat domain proteins: a novel target class?

(2017) Matthieu Schapira et al.   NATURE REVIEWS DRUG DISCOVERY

PI3K/AKT-mediated upregulation of WDR5 promotes colorectal cancer metastasis by directly targeting ZNF407

(2017) Xin Tan et al.   Cell Death & Disease

The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice

(2016) Elizabeth C. Townsend et al.   CANCER CELL

Epigenetic Perturbations by Arg882-Mutated DNMT3A Potentiate Aberrant Stem Cell Gene-Expression Program and Acute Leukemia Development

(2016) Rui Lu et al.   CANCER CELL

High-affinity small molecular blockers of mixed lineage leukemia 1 (MLL1)-WDR5 interaction inhibit MLL1 complex H3K4 methyltransferase activity

(2016) Dong-Dong Li et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Structure-Based Optimization of a Small Molecule Antagonist of the Interaction Between WD Repeat-Containing Protein 5 (WDR5) and Mixed-Lineage Leukemia 1 (MLL1)

(2016) Matthäus Getlik et al.   JOURNAL OF MEDICINAL CHEMISTRY

Induced protein degradation: an emerging drug discovery paradigm

(2016) Ashton C. Lai et al.   NATURE REVIEWS DRUG DISCOVERY

PROTAC-induced BET protein degradation as a therapy for castration-resistant prostate cancer

(2016) Kanak Raina et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

In Vivo Functional Platform Targeting Patient-Derived Xenografts Identifies WDR5-Myc Association as a Critical Determinant of Pancreatic Cancer

(2016) Alessandro Carugo et al.   Cell Reports

An Alternative Approach to ChIP-Seq Normalization Enables Detection of Genome-Wide Changes in Histone H3 Lysine 27 Trimethylation upon EZH2 Inhibition

(2016) Brian Egan et al.   PLoS One

HaloPROTACS: Use of Small Molecule PROTACs to Induce Degradation of HaloTag Fusion Proteins

(2015) Dennis L. Buckley et al.   ACS Chemical Biology

WDR5 Supports an N-Myc Transcriptional Complex That Drives a Protumorigenic Gene Expression Signature in Neuroblastoma

(2015) Y. Sun et al.   CANCER RESEARCH

Interaction with WDR5 Promotes Target Gene Recognition and Tumorigenesis by MYC

(2015) Lance R. Thomas et al.   MOLECULAR CELL

Gain-of-function p53 mutants co-opt chromatin pathways to drive cancer growth

(2015) Jiajun Zhu et al.   NATURE

Pharmacological targeting of the Wdr5-MLL interaction in C/EBPα N-terminal leukemia

(2015) Florian Grebien et al.   Nature Chemical Biology

Catalytic in vivo protein knockdown by small-molecule PROTACs

(2015) Daniel P Bondeson et al.   Nature Chemical Biology

WDR5 Expression Is Prognostic of Breast Cancer Outcome

(2015) Xiaofeng Dai et al.   PLoS One

Upregulated WDR5 promotes proliferation, self-renewal and chemoresistance in bladder cancer via mediating H3K4 trimethylation

(2015) Xu Chen et al.   Scientific Reports

Selective inhibition of EZH2 and EZH1 enzymatic activity by a small molecule suppresses MLL-rearranged leukemia

(2014) B. Xu et al.   BLOOD

Targeting MLL1 H3K4 Methyltransferase Activity in Mixed-Lineage Leukemia

(2014) Fang Cao et al.   MOLECULAR CELL

Improved vectors and genome-wide libraries for CRISPR screening

(2014) Neville E Sanjana et al.   NATURE METHODS

Genomic impact of transient low-dose decitabine treatment on primary AML cells

(2013) J. M. Klco et al.   BLOOD

Genome engineering using the CRISPR-Cas9 system

(2013) F Ann Ran et al.   Nature Protocols

Genome-Scale CRISPR-Cas9 Knockout Screening in Human Cells

(2013) Ophir Shalem et al.   SCIENCE

Synthesis, Optimization, and Evaluation of Novel Small Molecules as Antagonists of WDR5-MLL Interaction

(2013) Yuri Bolshan et al.   ACS Medicinal Chemistry Letters

Small-molecule inhibition of MLL activity by disruption of its interaction with WDR5

(2012) Guillermo Senisterra et al.   BIOCHEMICAL JOURNAL

Structural Basis for WDR5 Interaction (Win) Motif Recognition in Human SET1 Family Histone Methyltransferases

(2012) Venkatasubramanian Dharmarajan et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

High-Affinity, Small-Molecule Peptidomimetic Inhibitors of MLL1/WDR5 Protein–Protein Interaction

(2012) Hacer Karatas et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

An H3K36 Methylation-Engaging Tudor Motif of Polycomb-like Proteins Mediates PRC2 Complex Targeting

(2012) Ling Cai et al.   MOLECULAR CELL

iMOSFLM: a new graphical interface for diffraction-image processing withMOSFLM

(2011) T. Geoff G. Battye et al.   ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY

RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome

(2011) Bo Li et al.   BMC BIOINFORMATICS

Single-vector inducible lentiviral RNAi system for oncology target validation

(2011) Dmitri Wiederschain et al.   CELL CYCLE

A User's Guide to the Encyclopedia of DNA Elements (ENCODE)

(2011)   PLOS BIOLOGY

PHENIX: a comprehensive Python-based system for macromolecular structure solution

(2010) Paul D. Adams et al.   ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY

Fast and accurate long-read alignment with Burrows–Wheeler transform

(2010) Heng Li et al.   BIOINFORMATICS

MapSplice: Accurate mapping of RNA-seq reads for splice junction discovery

(2010) Kai Wang et al.   NUCLEIC ACIDS RESEARCH

Differential expression analysis for sequence count data

(2010) Simon Anders et al.   GENOME BIOLOGY

electronic Ligand Builder and Optimization Workbench(eLBOW): a tool for ligand coordinate and restraint generation

(2009) Nigel W. Moriarty et al.   ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY

WDR5, a complexed protein

(2009) Raymond C Trievel et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Structure of WDR5 Bound to Mixed Lineage Leukemia Protein-1 Peptide

(2008) Anamika Patel et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

A Conserved Arginine-containing Motif Crucial for the Assembly and Enzymatic Activity of the Mixed Lineage Leukemia Protein-1 Core Complex

(2008) Anamika Patel et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Model-based Analysis of ChIP-Seq (MACS)

(2008) Yong Zhang et al.   GENOME BIOLOGY