Human carbonic anhydrase modulators: the past, present, and future.

Human carbonic anhydrases (hCAs) are a superfamily of metalloenzymes with considerable, though yet poorly exploited therapeutic potential. They were primarily implicated in ocular and renal diseases and are targeted by antiglaucoma and diuretic drugs. However, emerging evidence has expanded our understanding of the roles of hCA modulators in other pathologies, including obesity, inflammation, hypoxic tumors, neurodegeneration, and neuropathic pain. In this review, we trace the evolution of our knowledge of hCA modulators, from their discovery to recent advances and future prospects. We also highlight the dysregulation of CAs in various diseases and current progress in developing hCA modulators for therapeutic use.