Latest findings on the role played by human isoform 5 of lactate dehydrogenase (hLDH5) in the promotion of glycolysis in invasive tumour cells are indicating this enzyme subtype as 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 hLDH5displaying remarkable potencies and selectivities. This review provides an overview of the newly developed hLDH5-inhibitors. The roles of hLDH isoforms will be briefly discussed, then the inhibitors will be grouped into chemical classes. Furthermore, general pharmacophore features will be emphasized throughout the structural subgroups analyzed.

Small-molecule inhibitors of human LDH5

GRANCHI, CARLOTTA;PATERNI, ILARIA;RANI, RESHMA;MINUTOLO, FILIPPO
2013

Abstract

Latest findings on the role played by human isoform 5 of lactate dehydrogenase (hLDH5) in the promotion of glycolysis in invasive tumour cells are indicating this enzyme subtype as 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 hLDH5displaying remarkable potencies and selectivities. This review provides an overview of the newly developed hLDH5-inhibitors. The roles of hLDH isoforms will be briefly discussed, then the inhibitors will be grouped into chemical classes. Furthermore, general pharmacophore features will be emphasized throughout the structural subgroups analyzed.
Granchi, Carlotta; Paterni, Ilaria; Rani, Reshma; Minutolo, Filippo
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/271136
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