Research Projects

Extensive research has revealed that the Polycomb Repressive Complex 1 (PRC1) plays a critical role in the initiation and progression of various cancer types. PRC1 consists of both enzymatic and non-enzymatic components, among which RING1B and BMI1 are prominent contributors to oncogenesis. Notably, overexpression of BMI1 has been correlated with the progression of leukemia as well as breast, lung, and hematologic malignancies. In contrast, RING1B is primarily implicated in breast cancer. These findings suggest that the PRC1 core may serve as a promising therapeutic target for cancer treatment. To date, several smallmolecule PRC1 inhibitors, such as RB-3, MS-147, and MS-181, have been developed. However, these agents have demonstrated limited efficacy in eradicating diverse cancer cell types. This highlights the need for more potent and selective therapeutic strategies aimed at disrupting PRC1 activity. Proteolysis-targeting chimeras (PROTACs) have emerged as an innovative class of heterobifunctional molecules capable of inducing the targeted degradation of disease-relevant proteins via the ubiquitin-proteasome system (UPS). PRC1 and PRC2 are two key protein complexes within the Polycomb group (PcG) family. A novel degrader-based approach has been proposed to facilitate the degradation of proteinprotein interaction partners more efficiently than the direct PROTAC-binding target itself. In this context, we hypothesize that the therapeutic candidate induces degradation of PRC1 subunits—specifically BMI1 and RING1B—while preferentially interacting with the EED subunit of PRC2. Despite the potential of PROTACs, several limitations restrict their broader application. These include: (i) challenges in achieving cell and tissue specificity, as seen with modalities like CLIPTAC, CHAMP, and molecular glues; (ii) inadequate cell permeability in certain types, such as PHOTACs; and (iii) poor solubility and bioavailability due to high molecular weight, as observed in platforms like SPNPRO, Floate-PROTAC, AbTAC, RIBOTAC, TFTAC, and bioPROTACs. Furthermore, a major limitation is that PROTACs function only on intracellular targets and rely on a limited pool of E3 ligases—of which only approximately 2% have been characterized for targeted protein degradation. Given these challenges, there is a compelling need for the identification and development of a novel PRC1 degrader with improved pharmacological properties. Such an approach holds the potential to overcome the complexity of cancer biology and enhance therapeutic outcomes in malignancies driven by PRC1 dysregulation. Finally, my research aims to develop a novel small-molecule degrader targeting PRC1 for cancer therapy.