Therapeutic Targeting of MonoPARP
To date, the function of monoPARPs have been relatively unstudied, in part, due to the difficulty in identifying the proteins that are modified and the biological pathways that are regulated. New understanding of monoPARPs has recently emerged, including significant contributions to the field by Ribon’s scientific founders. In recent years, Ribon’s Vice President of Discovery Biology, Paul Chang (then an Assistant Professor at MIT) and professors Lee Kraus of UT Southwestern Medical Center and Tim Mitchison at Harvard Medical School made fundamental discoveries on the function of monoPARPs and polyPARPs, identifying new roles in multiple cellular stress responses and functions in cellular organization and in gene expression. MonoPARPs regulate these stress responses by modifying the function of key regulatory proteins with the covalent attachment of ADP-ribose, a reaction called MARylation. This mechanism is so essential to biology that it has evolved separately in viruses, bacteria and animals as a key regulator of protein function.
Ribon is building upon the early biological insights of its scientific founders to create an integrated technology platform to interrogate monoPARPs and to discover and develop first-in-class, small molecule medicines that selectively target monoPARPs to treat cancer. Ribon may also apply its technology to discover new medicines that modulate monoPARPs for other diseases including inflammatory and neurodegenerative diseases. Key components of this integrated platform include biological tools such as recombinant DNA constructs, siRNAs, knockout cell lines and highly specific antibodies; and chemical tools such as small molecule probes and crystal structures and translational medicine tools. With 11 different monoPARPs, Ribon’s platform can be applied to investigate a wide range of potential new drug opportunities in hematologic and solid tumors.