A Small Molecule Targeting Oncogenic Pre-miR-21 and Their Use in the Treatment of Cancers
Design of small molecules that inhibit pre-cursor to oncogenic micro RNA-21 (pre-miR-2) Inhibitor with a novel mode of action (MOA) – cleavage of the transcript The compound inhibits breast cancer metastasis to lung
Targeted Degradation of the Oncogenic microRNA 17–92 Cluster by Structure-Targeting Ligands
A specific dimer to target three miRNAs in the cluster, miR-17, miR-18a, and miR-20a, to inhibit their biogenesis Direct cleavage by recruiting an endogenous nuclease, or a ribonuclease targeting chimera (RIBOTAC) The compound selectively reduced levels in polycystic kidney disease, prostate cancer, and breast cancer
Conversion of a Biologically Silent miRNA Binding Small Molecule to an miRNA Degrader
Drugging of RNA via antisense oligonucleotides (ASOs) and small molecules Efficacy limitations on the efficiency of ASO binding Biologically silent binding small molecule-mRNA have been conjugated with an RNase activator to degrade the RNA motif and negate its bioactivity
Targeted RNA Degradation Allows Precision Repurposing of Protein-Targeted Small Molecule Medicine to RNA
Repurposing of medicines has potential to accelerate treatments to patients RNA is considered nearly impossible to target directly with small molecules Dovitinib, targets receptor tyrosine kinases (RTKs) and binds to a functional site in the oncogenic microRNA precursor, pre-miR-21, inhibiting its processing A RIBOTAC of Dovitinib shifted the selectivity to pre-miR-21 by 2500-fold Targeted degradation […]
Defining Small Molecule Fragment Binding Transcriptome-Wide
A ribonuclease targeting chimera (RIBOTAC) to degrade QSOX1-mediated phenotypes in cancer cells such as triple negative breast cancer
miRNA Switches for RNA-Triggered Control of RNA Interference
A group of Orthogonal RNA Interference induced by Trigger RNA (ORIENTR) that can be switched on by cognate RNA triggers to induce RNAi in human cells ORIENTR devices act as signal transducers between input RNA trigger and output microRNA (miRNA) to induce RNAi