City of Hope

Sanford-burnham Medical Research Institute

Suvalent Therapeutics, Inc.

Sanford-burnham Medical Research Institute at Lake Nona

Yuan Chen

Yi-Jia Li

Ekaterina Bobkova

Greg Roth

Daniela Divlianska

David A Horne

Ted Charles Judd

Yang Su

Yuelong Ma

Xiaohu Ouyang

Andrew Namanja

Jun Pu

Pasha Khan

Angela L Perkins-Harki

Chih-Hong Chen

Sung Wook Yi

There are disclosed, inter alia, methods of inhibiting an E1 enzyme, and compounds useful for inhibiting an E1 enzyme.

SUMO inhibitor compounds and uses thereof

Provided herein are methods of detecting binding of an SENP1 polypeptide to a compound and methods for screening for inhibitors of SENP1. Further provided are aqueous compositions comprising SENP1 polypeptides and NMR apparatuses comprising the compositions for NMR analysis.

Methods of identifying SENP1 inhibitors

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

Arcadia, CA, United States of America

Yuan Chen