Small molecule recruitment modules for NR5A nuclear receptors
Innovative small molecule modules target NR5A nuclear receptors using synthetic molecular glue and bi-functional ligands. Effective in cancer and endometriosis, with potential for novel IP development. Validated in cell lines, progressing towards organoid testing and optimization.
Overview
Vanderbilt University Medical Center has developed cutting-edge small molecule recruitment modules aimed at regulating NR5A nuclear receptors, specifically NR5A1 and NR5A2. These modules utilize synthetic molecular glue and bi-functional ligands to interfere with phospholipid interactions, demonstrating potential efficacy in treating adrenocortical cancer and endometriosis. The development of PROTAC inhibitors shows promise in human cell lines, with ongoing efforts to enhance the targeting module through advanced crystallography and ultra-large library screening.
Technical specifications
- Target Receptors: NR5A1 (SF-1) and NR5A2 (LRH-1)
- Mechanism: Interferes with hydrophobic acyl chain binding, leveraging molecular glue for ligand interaction
- Current Development: Crystallography and computational screening of 23 billion compounds to identify novel scaffolds
- Validation: Preliminary efficacy in human 293T cells; testing in cancer and endometriosis cell lines and patient-derived organoids
- Optimization: Ongoing PK/PD optimization with potential for IP injection to treat ectopic endometriosis
Technology readiness level
This innovative technology is at TRL 4, indicating that it has been validated in laboratory environments and is moving towards more complex testing stages, including organoid and in vivo validation.
About Vanderbilt University Medical Center
Vanderbilt University Medical Center is a large, independent academic medical center and health system in Nashville, uniting patient care, research, and training at scale. Co-located hospitals and research facilities give partners access to core labs, biobanking, advanced imaging, and secure, de‑identified EHR data resources. A centralized trials office, experienced contracting, and proximity to Nashville’s healthcare management cluster streamline multi-site studies and real‑world evidence work. Research is backed by competitive federal funding, led by NIH and complemented by DoD and CDC. A dedicated technology transfer office supports IP, licensing, and startup formation to accelerate clinical translation.
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