Epigeneticmodificationsin eukaryoticbiologicalpathwayscanleadtotheup-ordownregulationofregulatoryproteinscontributingtodiseaseonsetandprogression.In thelastthreedecades,histonedeacety-lases(HDACs)are amongthemoststudiedepigenetictargets.In fact,aberrantHDACexpressionis associatedwithnumeroustypesofcancerandneurodegenerativedisorders,makingHDACspromisingmoleculartargetsforthedesignof newdrugs.ManyHDACinhibitors(HDACi)are currentlyin clinicalevaluationforvarioustypesofcancer, andsomeofthemhavereachedthemarketafterapprovalbytheFoodandDrugAdministration(FDA).ThepresentreviewsummarizesthevariousHDACclassesandrelativeisoforms.Thenwediscussdiffer-entclassesorisoform-selectiveHDACiwitha strongemphasisonlate-stagepreclinicalcandidatesanddrugsin clinicalstudies.Lastbutnotleast,weshedlightonthepharmacokineticchallengesandfuture directionsinHDACidesign.
Current HDAC Inhibitors in Clinical Trials / DI BELLO, Elisabetta; Noce, Beatrice; Fioravanti, Rossella; Mai, Antonello. - In: CHIMIA. - ISSN 0009-4293. - 76:5(2022), pp. 448-453. [10.2533/chimia.2022.448]
Current HDAC Inhibitors in Clinical Trials
Elisabetta Di Bello;Beatrice Noce;Rossella Fioravanti
;Antonello Mai
2022
Abstract
Epigeneticmodificationsin eukaryoticbiologicalpathwayscanleadtotheup-ordownregulationofregulatoryproteinscontributingtodiseaseonsetandprogression.In thelastthreedecades,histonedeacety-lases(HDACs)are amongthemoststudiedepigenetictargets.In fact,aberrantHDACexpressionis associatedwithnumeroustypesofcancerandneurodegenerativedisorders,makingHDACspromisingmoleculartargetsforthedesignof newdrugs.ManyHDACinhibitors(HDACi)are currentlyin clinicalevaluationforvarioustypesofcancer, andsomeofthemhavereachedthemarketafterapprovalbytheFoodandDrugAdministration(FDA).ThepresentreviewsummarizesthevariousHDACclassesandrelativeisoforms.Thenwediscussdiffer-entclassesorisoform-selectiveHDACiwitha strongemphasisonlate-stagepreclinicalcandidatesanddrugsin clinicalstudies.Lastbutnotleast,weshedlightonthepharmacokineticchallengesandfuture directionsinHDACidesign.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
