Investigational drugs in early phase clinical trials targeting thermotransient receptor potential (thermoTRP) channels

Abstract

Introduction: Thermo transient receptor potential (thermoTRP) channels are some of the most inten sely pursued therapeutic targets of the past decade. They are considered promising targets of numer ous diseases including chronic pain and cancer. Modulators of these proteins, in particular TRPV1-4, TRPM8 and TRPA1, have reached clinical development, but none has been approved for clinical practice yet. Areas covered: The therapeutic potential of targeting thermoTRP channels is discussed. The discussion is centered on our experience and on available data found in SciFinder, PubMed, and ClinicalTrials.gov database from the past decade. This review focuses on the therapeutic progress concerning this family of channels, including strategies to improve their therapeutic index for overcoming adverse effects. Expert opinion: Although thermoTRPs are pivotal drug targets, translation to the clinic has faced two key problems, (i) unforeseen side effects in Phase I trials and, (ii) poor clinical efficacy in Phase II trials. Thus, there is a need for (i) an enhanced understanding of the physiological role of these channels in tissues and organs and (ii) the development of human-based pre-clinical models with higher clinical translation. Furthermore, progress in nanotechnology-based delivery strategies will positively impact thermoTRP human pharmacology.