Over the last three decades, the scaffold proteins prohibitins-1 and -2 (PHB1/2) have emerged as key signaling proteins regulating a myriad of signaling pathways in health and diseases. Small molecules targeting PHBs display promising effects against cancers, osteoporosis, inflammatory, cardiac and neurodegenerative diseases. This review provides an updated overview of the various classes of PHB ligands, with an emphasis on their mechanism of action and therapeutic potential. We also describe how these ligands have been used to explore PHB signaling in different physiological and pathological settings.
Keywords: Alzheimer disease; Autoimmune disease; C-RAF; Cancer; Cardiac diseases; Cardio-oncology; Cell signaling; Drug discovery; Inflammation; KRAS; LC3; MAP kinase; Melanogenesis; Mitophagy; NF-kB; Osteoclastogenesis; Osteoporosis; Parkinson disease; RAF1; Scaffold proteins; Wnt.