Chemistry for the Identification of Therapeutic Targets: Recent Advances and Future Directions

Abstract

The increasing availability of chemical probes for specific applications in chemical biology and medicinal chemistry is extensively facilitating our knowledge of biological systems. This understanding has fundamental implications in the development of new efficacious therapeutic strategies. Nowadays, successful drug discovery programs consider identification, engagement, and endogenous levels of the intended therapeutic target from the earliest preclinical stages. All these aspects are addressed with the use of chemical probes, compounds that rely on the use of a particular chemical reaction to give an answer to a specific biological question. In this review we will describe the underlying chemistry and the most recent advances experienced in the field together with their most important biomedical applications.

VOC-Based Probes, a New Set of Analytical Tools to Monitor Patient Health from Blood Sample. Proof of Concept on Tracking COVID-19 Infection

“…Dysregulation of enzyme activity is a hallmark of many diseases. Developing accurate and sensitive strategies to characterize disease-associated enzyme activities is crucial for the fields of diagnosis, prognosis, and drug discovery. − Continuous efforts are being deployed to design new approaches that could provide fundamental insights into these metabolic markers. Within this framework, proteomics hold a central position with the development of multiplex workflows involving antibody-based approaches, electrophoresis methodology, mass-spectrometry analysis, or enzymatic assays. − Although these methodologies showed high specificity, they cannot provide information on enzyme functionality in their physiological environment.…”

Induced-volatolomics for the design of tumour activated therapy

“…Current therapeutic arsenal includes numerous enzyme inhibitors [3] and enzyme-responsive antibody-drug conjugates [4] for the treatment of a wide range of malignancies. Thus, the design of novel strategies dedicated to the exploration of tumourassociated enzymes is of prime importance for cancer therapy and diagnosis [5,6] . Within this framework, activable imaging probes have been developed to detect the dysregulation of some enzyme activities in tumours [7][8][9][10][11][12][13][14][15] .…”

Induced-volatolomics for the design of tumour activated therapy

“…Current therapeutic arsenal includes numerous enzyme inhibitors 3 and enzyme-responsive antibody-drug conjugates 4 for the treatment of a wide range of malignancies. Thus, the design of novel strategies dedicated to the exploration of tumour-associated enzymes is of prime importance for cancer therapy and diagnosis 5,6 . Within this framework, activable imaging probes have been developed to detect the dysregulation of some enzyme activities in tumours [7][8][9][10][11][12][13][14][15][16][17] .…”

“…Thus, the design of novel strategies dedicated to the exploration of tumour-associated enzymes is of prime importance for cancer therapy and diagnosis. 5,6 Within this framework, activable imaging probes have been developed to detect the dysregulation of some enzyme activities in tumours. [7][8][9][10][11][12][13][14][15][16][17] However, most of these turnon probes suffer from low signal penetration depth and background noise.…”