City of Hope

Sanford-burnham Medical Research Institute

Sanford-burnham Medical Research Institute at Lake Nona

Yi-Jia Li

Yuan Chen

Daniela Divlianska

Ekaterina Bobkova

Greg Roth

David A Horne

Yang Su

Yuelong Ma

Jun Pu

Pasha Khan

Angela L Perkins-Harki

According to the embodiments described herein, a SUMOylation inhibitor compound comprising a singleton scaffold is provided. In some embodiments, a method for inhibiting a SUMOylation enzyme in a cell is provided. Such a method may include administering a SUMOylation inhibitor compound to the cell. In some aspects, the SUMOylation enzyme is SUMO E1 or SUMO E2. In some aspects, the method may be used to inhibit a cancer cell in vitro (e.g., grown in culture) or in vivo (e.g., as part of a tumor in a subject). In other embodiments, a method for treating a cancer, degenerative diseases and viral infection is provided. Such a method may include administering an effective amount of a pharmaceutical composition to a subject having the cancer. The pharmaceutical composition may include a singleton SUMOylation inhibitor compound. In some embodiments, the method for treating a cancer may further comprise administering one or more DNA-damaging therapy in combination with administration of the pharmaceutical composition.

Singleton inhibitors of sumoylation enzymes and methods for their use

According to the embodiments described herein, a methods for inhibiting small ubiquitin-like modifier enzymes in a cell are provided. Such methods may include administering certain substituted pyrrolo[2,3-b]-quinoxalines to the cell. In some aspects, the small ubiquitin-like modifier enzyme is SUMO E1 or SUMO E2. In some aspects, the methods may be used to inhibit a cancer cell in vitro (e.g., grown in culture) or in vivo (e.g., as part of a tumor in a subject). In other embodiments, methods for treating a cancer, degenerative diseases and viral infection are provided. Such methods may include administering an effective amount of a pharmaceutical composition to a subject having cancer. The pharmaceutical composition may include a small ubiquitin-like modifier inhibitor compound. In some embodiments, the method for treating a disease may further comprise administering one or more DNA-damaging therapy in combination with administration of the pharmaceutical composition.

Inhibition of small ubiquitin-like modifier enzymes with substituted pyrrolo[2,3-b]quinoxalines

A composition used to develop a reagent for investigating Ubl-modifications in cellular functions and in the treatment of cancer is provided. The composition comprises gold nanoparticle (AuNP)-ligand conjugates that include at least two components: gold nanoparticles (AuNPs) and modified ubiquitin- or ubiquitin-like interacting motif (UIM or ULIM) mimetics. In one embodiment, the modified ULM mimetic is a modified SUMO interaction motif (SIM) mimetic. According to the embodiments described herein, the compound inhibits ubiquitin- or ubiquitin-like protein (Ubl)-mediated protein-protein interactions and sensitizes cells to ionizing radiation. The modified UIM and ULIM mimetics may be conjugated to the AuNP such that each AuNP is conjugated to a plurality of modified UIM or ULIM mimetics. The modified ULIM mimetics may be conjugated to the AuNP via a thiol group.

Multi-valent poly-Ubl chain inhibitors and methods of use

Growing community of inventors

Duarte, CA, United States of America

Yi-Jia Li