(1059-D) ReFRAME: Empowering Drug Repurposing Through an Open-Access Library of 12,500 Compounds for Broad-Spectrum High-Throughput Screening
Tuesday, February 6, 2024
2:00 PM – 3:00 PM EST
Location: Exhibit Halls AB
Abstract: In the High-Throughput Drug Screening community, there is a need for large chemical libraries that are not only highly curated but are also accessible to all fields of study and particularly those where there is low commercial motivation for costly research. The chemical diversity and known safety profiles of drugs previously tested in humans are continually being collected and updated to make this valuable set of compounds to explore potential therapeutic utility in indications outside those originally targeted. This practice of “drug repurposing” has become commonplace in academic and other nonprofit drug-discovery efforts, with the appeal that significantly less time and resources are required to advance a candidate into the clinic. At Calibr, a Division of Scripps Research, we have a comprehensive open-access, drug repurposing screening set termed ReFRAME (Repurposing, Focused Rescue, and Accelerated Medchem). The library was assembled by combining multiple widely used drug competitive intelligence databases including Clarivate Integrity, GVK Excelra GoStar, and Citeline Pharmaprojects, together with extensive patent mining of small molecules that have completed the IND-enabling phase. To date, ~12,500 compounds have been assembled and subsequently plated for screening, with an additional ~800 compounds which have been identified to be acquired as Calibr continues to compile the most up-to-date information. The ReFRAME library is a free resource in which research teams are encouraged to screen against a multitude of disease indications and receive feedback from our team. All screens go through a standard workflow in which Calibr delivers Assay Ready Plates (ARPs) for a single point primary screen. Up to 1% of the compounds can be selected for a follow up assay to confirm the hits in dose response, in duplicate. Once the screen has completed, the screening institution has one year to follow up on their findings before Calibr publishes the hit and a description of the assay on the open-access data portal (https://reframedb.org) for the use of furthering scientific exploration. In the 7 years since the creation of the sharable ReFRAME library, 145 screens have been completed and currently have the data published on the portal describing screens which encompass SARS-CoV-2, Tuberculosis, Contraception, Fibrosis, Dengue, Malaria, and many more. To exemplify ReFRAME’s utility, this collection was screened against Cryptosporidium spp., a major cause of childhood diarrhea in the developing world, and two active compounds previously tested in humans for other therapeutic indications were identified. Both compounds, VB-201 and a structurally related analog of ASP-7962, were subsequently shown to be efficacious in animal models of Cryptosporidium infection at clinically relevant doses, based on available human doses. The resulting data from ReFRAME screens is invaluable to drug discovery and development and will continue to make significant impact upon further use in the field.