title: Small-molecule inhibitors of human LDH5.
abstract: The latest findings on the role played by human LDH5 (hLDH5) in the promotion of glycolysis in invasive tumor cells indicates that this enzyme subtype is a promising therapeutic target for invasive cancer. Compounds able to selectively inhibit hLDH5 hold promise for the cure of neoplastic diseases. hLDH5 has so far been a rather unexplored target, since its importance in the promotion of cancer progression has been neglected for decades. This enzyme should also be considered as a challenging target due the high polar character (mostly cationic) of its ligand cavity. Recently, significant progresses have been reached with small-molecule inhibitors of hLDH5 displaying remarkable potencies and selectivities. This review provides an overview of the newly developed hLDH5 inhibitors. The roles of hLDH isoforms will be briefly discussed, and then the inhibitors will be grouped into chemical classes. Furthermore, general pharmacophore features will be emphasized throughout the structural subgroups analyzed.
authors.affiliation: Dipartimento di Farmacia, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Granchi
authors.forename: Ilaria
authors.initials: I
authors.lastname: Paterni
authors.forename: Reshma
authors.initials: R
authors.lastname: Rani
authors.forename: Filippo
authors.initials: F
authors.lastname: Minutolo
mesh_terms: D001393:Azoles / Q000737:chemistry / Q000378:metabolism; D002264:Carboxylic Acids / Q000737:chemistry / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism; D006072:Gossypol / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000080864:Lactate Dehydrogenase 5; D009281:Naphthalenes / Q000737:chemistry / Q000378:metabolism; D010072:Oxamic Acid / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D011804:Quinolines / Q000737:chemistry / Q000378:metabolism
chemical_list: D001393:Azoles; D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D007211:Indoles; D007527:Isoenzymes; D009281:Naphthalenes; D020033:Protein Isoforms; D011804:Quinolines; C085312:1-naphthoic acid; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D006072:Gossypol; D010072:Oxamic Acid