Invention novelty: Panel of newly-synthesized small molecule antagonists of PBX1-DNA interaction for the treatment of different cancers and other non-neoplastic diseases.
Value Proposition: Pre-B-cell leukemia homeobox-1 (PBX1) is a homeodomain transcription factor that interacts with DNA and other proteins to regulate a variety of biological processes such as organogenesis and maintaining pluripotency of stem cells. Transcriptional over-activation by PBX1 has been implicated in different human diseases including cancer. Here, inventors identified a panel of small molecule inhibitors that directly interfere with PBX1-binding to DNA, valuable as powerful new therapeutics for the treatment of different human malignancies. Advantages include:
• Efficient anti-tumor activity via direct disruption of PBX1 interaction with DNA
• Improved aqueous solubility permits use in clinical studies
• Broad application as therapeutics for human cancers including Multiple Myeloma, ovarian cancer and potentially other non-neoplastic diseases
Technical Details: Johns Hopkins researchers have synthesized a panel of small molecule antagonists of PBX1-DNA binding for the treatment of human cancer. The described compounds show satisfactory aqueous solubility, making them the first compounds of this class to be suitable for clinical studies. Interestingly, unlike other existing compounds that interfere with protein-protein interactions, the disclosed molecules directly block PBX1-binding to DNA, resulting in highly efficient suppression of PBX1-target gene expression and robust cytotoxicity in platinum-resistant cancer cells. This is further substantiated by a potent anti-tumor activity observed in several in vivo mouse tumor models for ovarian cancer, multiple myeloma, and pancreatic cancer, hence, presenting a powerful new therapeutic strategy to treat multiple human cancers characterized by aberrant PBX1 activity. In addition, PBX1 may also affect the functions of hyper-activated immune cells and therefore, the identified compounds can potentially have applications in other diseases such as autoimmune diseases.
Looking for Partners: Seeking investment and partnership to expeditiously move this small molecule drug candidate into IND-enabling studies and the clinic.
Stage of Development: Pre-Clinical
Data Availability: Animal Data
