Small-molecule RNA ligands: a patent review (2018-2024)

Introduction: Targeting three-dimensional RNA structures with traditional drug-like small molecules is gaining wide attention in both the academia and the pharmaceutical industries, due to their good oral bioavailability, cheap production cost, and the possibility of fine-tuning ADMET properties, which represent a powerful alternative to the current RNA-targeted therapies, including ASO and siRNA. As RNAs are involved in nearly all the physiological and pathological processes, small molecules RNA ligands can have a plethora of different therapeutic applications, spanning from cancer to infectious and neurological diseases. Areas covered: This review describes patents concerning small molecules RNA ligands published within January 2018 and October 2024, searched through Espacenet, Patentscope, and Google Patents databases. Expert opinion: The number of patents that has been released in the last few years demonstrates the relevance of targeting RNA structures for the development of next generation chemotherapeutic agents and antiviral/antibacterial drugs, even though this field is still in its infancy and many issues still need to be resolved, in particular related to selectivity. An emerging approach to considerably limiting side effects is presented by RIBOTAC derivatives, as promoting a selective RNase-L mediated RNA degradation allows to significantly reduce the dose of the compound.