Contemporary Progress and Opportunities in RNA-Targeted Drug Discovery

Rational Approach to Identify RNA Targets of Natural Products Enables Identification of Nocathiacin as an Inhibitor of an Oncogenic RNA

(2022) Fei Ye et al.   ACS Chemical Biology

The Biochemical Landscape of Riboswitch Ligands

(2022) Ronald R. Breaker   BIOCHEMISTRY

DNA-encoded library versus RNA-encoded library selection enables design of an oncogenic noncoding RNA inhibitor

(2022) Raphael I. Benhamou et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

R-BIND 2.0: An Updated Database of Bioactive RNA-Targeting Small Molecules and Associated RNA Secondary Structures

(2022) Anita Donlic et al.   ACS Chemical Biology

Targeting Xist with compounds that disrupt RNA structure and X inactivation

(2022) Rodrigo Aguilar et al.   NATURE

SHAPE-enabled fragment-based ligand discovery for RNA

(2022) Meredith J. Zeller et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

An orally available, brain penetrant, small molecule lowers huntingtin levels by enhancing pseudoexon inclusion

(2022) Caroline Gubser Keller et al.   Nature Communications

Affinity-Based Profiling of the Flavin Mononucleotide Riboswitch

(2022) Stefan Crielaard et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Transcriptome-Wide Mapping of Small-Molecule RNA-Binding Sites in Cells Informs an Isoform-Specific Degrader of QSOX1 mRNA

(2022) Yuquan Tong et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Targeting RNA structures with small molecules

(2022) Jessica L. Childs-Disney et al.   NATURE REVIEWS DRUG DISCOVERY

Multiassay Profiling of a Focused Small Molecule Library Reveals Predictive Bidirectional Modulation of the lncRNA MALAT1 Triplex Stability In Vitro

(2022) Martina Zafferani et al.   ACS Chemical Biology

The promise of cryo-EM to explore RNA structural dynamics

(2022) Steve L. Bonilla et al.   JOURNAL OF MOLECULAR BIOLOGY

Machine Learning Informs RNA‐Binding Chemical Space

(2022) Kamyar Yazdani et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Study of an RNA-Focused DNA-Encoded Library Informs Design of a Degrader of a r(CUG) Repeat Expansion

(2022) Quentin M. R. Gibaut et al.   Journal of the American Chemical Society

Probing the dynamic RNA structurome and its functions

(2022) Robert C. Spitale et al.   NATURE REVIEWS GENETICS

Risdiplam, the First Approved Small Molecule Splicing Modifier Drug as a Blueprint for Future Transformative Medicines

(2021) Hasane Ratni et al.   ACS Medicinal Chemistry Letters

Discovery of Surfactins as Inhibitors of MicroRNA Processing Using Cat-ELCCA

(2021) Andrew W. Robertson et al.   ACS Medicinal Chemistry Letters

Reprogramming of Protein-Targeted Small-Molecule Medicines to RNA by Ribonuclease Recruitment

(2021) Peiyuan Zhang et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

A call for direct sequencing of full-length RNAs to identify all modifications

(2021) Juan D. Alfonzo et al.   NATURE GENETICS

Efficient NMR Screening Approach to Discover Small Molecule Fragments Binding Structured RNA

(2021) Matthew D. Shortridge et al.   ACS Medicinal Chemistry Letters

A chemical probe based on the PreQ1 metabolite enables transcriptome-wide mapping of binding sites

(2021) Sumirtha Balaratnam et al.   Nature Communications

Small molecule splicing modifiers with systemic HTT-lowering activity

(2021) Anuradha Bhattacharyya et al.   Nature Communications

Advanced approaches for elucidating structures of large RNAs using NMR spectroscopy and complementary methods

(2020) Anita Kotar et al.   METHODS

How We Think about Targeting RNA with Small Molecules

(2020) Matthew G. Costales et al.   JOURNAL OF MEDICINAL CHEMISTRY

Gini Coefficients as a Single Value Metric to Define Chemical Probe Selectivity

(2020) Andrei Ursu et al.   ACS Chemical Biology

A large-scale binding and functional map of human RNA-binding proteins

(2020) Eric L. Van Nostrand et al.   NATURE

Regulation of MALAT1 triple helix stability and in vitro degradation by diphenylfurans

(2020) Anita Donlic et al.   NUCLEIC ACIDS RESEARCH

Inhibition of RNA-binding proteins with small molecules

(2020) Peng Wu   Nature Reviews Chemistry

PEARL-seq: A Photoaffinity Platform for the Analysis of Small Molecule-RNA Interactions

(2020) Herschel Mukherjee et al.   ACS Chemical Biology

19 F NMR‐Based Fragment Screening for 14 Different Biologically Active RNAs and 10 DNA and Protein Counter‐Screens

(2020) Oliver Binas et al.   CHEMBIOCHEM

IRES-targeting small molecule inhibits enterovirus 71 replication via allosteric stabilization of a ternary complex

(2020) Jesse Davila-Calderon et al.   Nature Communications

Targeting the SARS-CoV-2 RNA Genome with Small Molecule Binders and Ribonuclease Targeting Chimera (RIBOTAC) Degraders

(2020) Hafeez S. Haniff et al.   ACS Central Science

A general fragment-based approach to identify and optimize bioactive ligands targeting RNA

(2020) Blessy M. Suresh et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Selective small molecule targeting of a triple helix encoded by the long non-coding RNA, MALAT1

(2019) Fardokht A Abulwerdi et al.   ACS Chemical Biology

RNA structure maps across mammalian cellular compartments

(2019) Lei Sun et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

RNA-ALIS: Methodology for screening soluble RNAs as small molecule targets using ALIS affinity-selection mass spectrometry

(2019) Noreen F. Rizvi et al.   METHODS

Synthetic ligands for PreQ1 riboswitches provide structural and mechanistic insights into targeting RNA tertiary structure

(2019) Colleen M. Connelly et al.   Nature Communications

Evidence for ligandable sites in structured RNA throughout the Protein Data Bank

(2019) William M. Hewitt et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Methods to identify and optimize small molecules interacting with RNA (SMIRNAS)

(2019) Andrei Ursu et al.   DRUG DISCOVERY TODAY

The roles of structural dynamics in the cellular functions of RNAs

(2019) Laura R. Ganser et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

RNA-targeted drug discovery: moving beyond promiscuous small-molecule scaffolds

(2019) Amanda L Garner   Future Medicinal Chemistry

Targeting RNA with Small Molecules: Identification of Selective, RNA-Binding Small Molecules Occupying Drug-Like Chemical Space

(2019) Noreen F. Rizvi et al.   SLAS Discovery

Discovery of Selective RNA-Binding Small Molecules by Affinity-Selection Mass Spectrometry

(2018) Noreen F. Rizvi et al.   ACS Chemical Biology

RNA-modifying proteins as anticancer drug targets

(2018) P. Ann Boriack-Sjodin et al.   NATURE REVIEWS DRUG DISCOVERY

Principles for targeting RNA with drug-like small molecules

(2018) Katherine Deigan Warner et al.   NATURE REVIEWS DRUG DISCOVERY

A brave new world of RNA-binding proteins

(2018) Matthias W. Hentze et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Discovery of Small Molecule Ligands for MALAT1 by Tuning an RNA-Binding Scaffold

(2018) Anita Donlic et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Discovery of Risdiplam, a Selective Survival of Motor Neuron-2 (SMN2) Gene Splicing Modifier for the Treatment of Spinal Muscular Atrophy (SMA)

(2018) Hasane Ratni et al.   JOURNAL OF MEDICINAL CHEMISTRY

A Massively Parallel Selection of Small Molecule-RNA Motif Binding Partners Informs Design of an Antiviral from Sequence

(2018) Jessica L. Childs-Disney et al.   Chem

Small molecules that target group II introns are potent antifungal agents

(2018) Olga Fedorova et al.   Nature Chemical Biology

Small Molecule Inhibition of microRNA-210 Reprograms an Oncogenic Hypoxic Circuit

(2017) Matthew G. Costales et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Nusinersen, an antisense oligonucleotide drug for spinal muscular atrophy

(2017) David R Corey   NATURE NEUROSCIENCE

Safety and efficacy findings in the first-in-human trial (FIH) of the oral splice modulator branaplam in type 1 spinal muscular atrophy (SMA): interim results

(2017) L. Charnas et al.   NEUROMUSCULAR DISORDERS

The RNA modification landscape in human disease

(2017) Nicky Jonkhout et al.   RNA

Binding to SMN2 pre-mRNA-protein complex elicits specificity for small molecule splicing modifiers

(2017) Manaswini Sivaramakrishnan et al.   Nature Communications

Microarray-based technologies for the discovery of selective, RNA-binding molecules

(2016) Fardokht A. Abulwerdi et al.   METHODS

Design of a small molecule against an oncogenic noncoding RNA

(2016) Sai Pradeep Velagapudi et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Design of a bioactive small molecule that targets r(AUUCU) repeats in spinocerebellar ataxia 10

(2016) Wang-Yong Yang et al.   Nature Communications

Small Molecule Inhibition of miR-544 Biogenesis Disrupts Adaptive Responses to Hypoxia by Modulating ATM-mTOR Signaling

(2015) Christopher L. Haga et al.   ACS Chemical Biology

Small Molecule Targeting of a MicroRNA Associated with Hepatocellular Carcinoma

(2015) Jessica L. Childs-Disney et al.   ACS Chemical Biology

Evidence That Antibiotics Bind to Human Mitochondrial Ribosomal RNA Has Implications for Aminoglycoside Toxicity

(2015) Seoyeon Hong et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Selective small-molecule inhibition of an RNA structural element

(2015) John A. Howe et al.   NATURE

SMN2 splice modulators enhance U1–pre-mRNA association and rescue SMA mice

(2015) James Palacino et al.   Nature Chemical Biology

Targeting the r(CGG) Repeats That Cause FXTAS with Modularly Assembled Small Molecules and Oligonucleotides

(2014) Tuan Tran et al.   ACS Chemical Biology

Two-dimensional combinatorial screening enables the bottom-up design of a microRNA-10b inhibitor

(2014) Sai Pradeep Velagapudi et al.   CHEMICAL COMMUNICATIONS

Sequence-based design of bioactive small molecules that target precursor microRNAs

(2014) Sai Pradeep Velagapudi et al.   Nature Chemical Biology

SMN2 splicing modifiers improve motor function and longevity in mice with spinal muscular atrophy

(2014) N. A. Naryshkin et al.   SCIENCE

Defining RNA motif–aminoglycoside interactions via two-dimensional combinatorial screening and structure–activity relationships through sequencing

(2013) Sai Pradeep Velagapudi et al.   BIOORGANIC & MEDICINAL CHEMISTRY

A Novel Role of Cytosolic Protein Synthesis Inhibition in Aminoglycoside Ototoxicity

(2013) S. P. Francis et al.   JOURNAL OF NEUROSCIENCE

Induction and reversal of myotonic dystrophy type 1 pre-mRNA splicing defects by small molecules

(2013) Jessica L. Childs-Disney et al.   Nature Communications

Landscape of transcription in human cells

(2012) Sarah Djebali et al.   NATURE

Identifying the preferred RNA motifs and chemotypes that interact by probing millions of combinations

(2012) Tuan Tran et al.   Nature Communications

Molecular Recognition of 6′-N-5-Hexynoate Kanamycin A and RNA 1x1 Internal Loops Containing CA Mismatches

(2011) Tuan Tran et al.   BIOCHEMISTRY

Defining the RNA Internal Loops Preferred by Benzimidazole Derivatives via 2D Combinatorial Screening and Computational Analysis

(2011) Sai Pradeep Velagapudi et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

A modified fluorescent intercalator displacement assay for RNA ligand discovery

(2010) Papa Nii Asare-Okai et al.   ANALYTICAL BIOCHEMISTRY

Structure-Activity Relationships through Sequencing (StARTS) Defines Optimal and Suboptimal RNA Motif Targets for Small Molecules

(2010) Sai Pradeep Velagapudi et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Two-Dimensional Combinatorial Screening of a Bacterial rRNA A-Site-like Motif Library: Defining Privileged Asymmetric Internal Loops That Bind Aminoglycosides

(2010) Tuan Tran et al.   BIOCHEMISTRY

Fluorescent Indicator Displacement Assay for Ligand−RNA Interactions

(2010) Jinhua Zhang et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Mitoxantrone Analogues as Ligands for a Stem−Loop Structure of Tau Pre-mRNA

(2009) Yang Liu et al.   JOURNAL OF MEDICINAL CHEMISTRY

Rational Design of Ligands Targeting Triplet Repeating Transcripts That Cause RNA Dominant Disease: Application to Myotonic Muscular Dystrophy Type 1 and Spinocerebellar Ataxia Type 3

(2009) Alexei Pushechnikov et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Two-dimensional combinatorial screening and the RNA Privileged Space Predictor program efficiently identify aminoglycoside–RNA hairpin loop interactions

(2009) Dustin J. Paul et al.   NUCLEIC ACIDS RESEARCH

Two-Dimensional Combinatorial Screening Identifies Specific 6′-Acylated Kanamycin A− and 6′-Acylated Neamine−RNA Hairpin Interactions†

(2008) Olga Aminova et al.   BIOCHEMISTRY