title: Lactate dehydrogenase inhibition: exploring possible applications beyond cancer treatment.
abstract: Lactate dehydrogenase (LDH) inhibition is considered a worthwhile attempt in the development of innovative anticancer strategies. Unfortunately, in spite of the involvement of several research institutions and pharma-companies, the discovery of LDH inhibitors with drug-like properties seems a hardly resolvable challenge. While awaiting new advancements, in the present review we will examine other pathologic conditions characterized by increased glycolysis and LDH activity, which could potentially benefit from LDH inhibition. The rationale for targeting LDH activity in these contexts is the same justifying the LDH-based approach in anticancer therapy: because of the enzyme position at the end of glycolytic pathway, LDH inhibitors are not expected to hinder glucose metabolism of normal cells. Moreover, we will summarize the latest contributions in the discovery of enzyme inhibitors and try to glance over the reasons underlying the complexity of this research.
authors.affiliation: Department of Experimental, Diagnostic & Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Di Stefano
authors.affiliation: Department of Experimental, Diagnostic & Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Manerba
authors.affiliation: Department of Experimental, Diagnostic & Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Di Ianni
authors.affiliation: Department of Experimental, Diagnostic & Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Fiume
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000927:Anticonvulsants / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D055808:Drug Discovery; D004734:Energy Metabolism; D004827:Epilepsy / Q000188:drug therapy / Q000201:enzymology; D006019:Glycolysis; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors*; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D010084:Oxidation-Reduction; D018406:Virus Physiological Phenomena
chemical_list: D000893:Anti-Inflammatory Agents; D000927:Anticonvulsants; D000970:Antineoplastic Agents; D007770:L-Lactate Dehydrogenase
keywords: cancer cell metabolism; epilepsy; glycolysis; immune-inflammatory diseases; lactate dehydrogenase; virus-induced metabolic changes