Expand the drug discovery toolbox to target Macrophage migration inhibitory factor in cancer

Lung cancer is the leading cause of cancer-related death worldwide, claiming 1.8 million victims (257, 000 in EU) in 2020. To unleash the capability of targeted therapy for lung cancer, which is limited by the heterogeneity and acquired drug resistance, it is imperative to discover and exploit previously unrecognized molecular mechanisms involved in cancer cell proliferation. A protein with a putatively central role in such mechanisms is macrophage migration inhibitory factor (MIF). To advance MIF-directed research, we leveraged medicinal chemistry and chemical biology approaches to develop small-molecule tools to explore its potential as drug target. MIF possesses various enzyme active sites and protein-protein interaction sites. We addressed the tautomerase active site, which overlaps with the CD74 receptor-binding site, by a novel fluorophore, which is capable to interfere with the MIF-CD74 interaction, and its fluorescent properties were utilized for development of a competition-based assay format to quantify binding to the MIF. Also for the MIF analogue, MIF2 small molecule modulators were developed. We developed the first potent MIF2 tautomerase inhibitor that exhibits robust inhibition on growth of lung cancer cells. Furthermore, a high affinity binder for the MIF tautomerase active site was employed to develop a novel potent MIF-targeted proteolysis targeting chimera (PROTAC), which enables elimination of MIF and inhibition of the proliferation of cancer cells. In addition, we developed fluorescent probes to facilitate cellular translocation studies on MIF and MIF2. Taken together, we provided a novel set of MIF-directed probes including several potential lung cancer therapeutics

Substituted thiophene compounds as d-dopachrome tautomerase inhibitors

The present invention relates to substituted thiophene compounds and methods useful for inhibiting D-dopachrome tautomerase. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders, notably cancer, such as NSCLC, and inflammation

Substituted thiophene compounds as d-dopachrome tautomerase inhibitors

The present invention relates to substituted thiophene compounds and methods useful for inhibiting D-dopachrome tautomerase. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders, notably cancer, such as NSCLC, and inflammation

Substituted thiophene compounds as d-dopachrome tautomerase inhibitors

The present invention relates to substituted thiophene compounds and methods useful for inhibiting D-dopachrome tautomerase. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders, notably cancer, such as NSCLC, and inflammation

Substituted thiophene compounds as d-dopachrome tautomerase inhibitors

The present invention relates to substituted thiophene compounds and methods useful for inhibiting D-dopachrome tautomerase. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders, notably cancer, such as NSCLC, and inflammation

Conformable electrochemical devices for closed-loop wound management

Chronic wounds arising from accidents, surgeries, or diseases impose a significant clinical and economic burden, underscoring the need for effective solutions to prevent severe complications. Recent advancements in materials science and electrochemical technology have facilitated the development of conformable electrochemical platforms for detection and management, incorporating monitoring, diagnosis, and treatment. Nevertheless, current wound detection and therapy systems face challenges related to the stability and specificity of sensor monitoring, as well as the need for on-site and comprehensive evaluation criteria to offer timely treatment guidance and follow-up care. This review provides a comprehensive overview of the closed-loop management system, emphasizing wound biomarker detection, wound assessment, and on-demand treatment, ultimately culminating in an integrated wound management approach by conformable electrochemical devices. Additionally, we explore the challenges, opportunities, and future prospects of soft and stretchable electrochemical biosensors, with the aim of enhancing the efficiency and timeliness of wound management