Multitarget inhibition of histone deacetylase (HDAC) and phosphatidylinositol-3-kinase (PI3K): Current and future prospects.

Multitarget inhibition of histone deacetylase (HDAC) and phosphatidylinositol-3-kinase (PI3K): Current and future prospects. ChemMedChem. 2020 Oct 13;: Authors: Fraga CAM, Rodrigues DA, Pinheiro PSM Abstract The discovery of HDACs inhibitors is a hot topic in the medicinal chemistry community regarding cancer research, which is related primarily to two factors: success in the clinics, e.g., the four FDA-approved HDAC inhibitors, and strong versatility to combine their pharmacophoric features to design new hybrid compounds with multitarget profile. Thus, selecting adequate pharmacophores to combine, i.e., combining targets that can result in a synergistic effect, is desirable, since it will increase the probability of discovering a new useful therapeutic strategy. In this work, we highlight the design of multitarget HDAC/PI3K inhibitors. Although this approach is still in earlier stages, many significant works describe the design and pharmacological evaluation of this new promising class of multitarget inhibitors, where compound CUDC-907 ( 12 ), which is already in clinical trials, stands out. Therefore, the question emerges of whether there still space for the design and evaluation of new multitarget HDAC/PI3K inhibitors. When considering the selectivity profile of the described multitarget compounds, the answer appears to be in the affirmative, especially since the first examples of compounds with a certain selectivity profile only ...
Source: ChemMedChem - Category: Chemistry Authors: Tags: ChemMedChem Source Type: research