Development of HDAC Inhibitors Exhibiting Therapeutic Potential in T-Cell Prolymphocytic Leukemia.
Animals
Antineoplastic Agents
/ chemical synthesis
Apoptosis
/ drug effects
Bendamustine Hydrochloride
/ pharmacology
Bridged Bicyclo Compounds, Heterocyclic
/ pharmacology
Cell Line, Tumor
Drug Synergism
Histone Deacetylase 6
/ metabolism
Histone Deacetylase Inhibitors
/ chemical synthesis
Humans
Hydroxamic Acids
/ chemical synthesis
Leukemia, Prolymphocytic, T-Cell
/ drug therapy
Male
Mice
Molecular Docking Simulation
Molecular Structure
Pyrrolidines
/ pharmacology
Structure-Activity Relationship
Sulfonamides
/ chemical synthesis
para-Aminobenzoates
/ pharmacology
Journal
Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531
Informations de publication
Date de publication:
24 06 2021
24 06 2021
Historique:
pubmed:
9
6
2021
medline:
26
8
2021
entrez:
8
6
2021
Statut:
ppublish
Résumé
Epigenetic targeting has emerged as an efficacious therapy for hematological cancers. The rare and incurable T-cell prolymphocytic leukemia (T-PLL) is known for its aggressive clinical course. Current epigenetic agents such as histone deacetylase (HDAC) inhibitors are increasingly used for targeted therapy. Through a structure-activity relationship (SAR) study, we developed an HDAC6 inhibitor KT-531, which exhibited higher potency in T-PLL compared to other hematological cancers. KT-531 displayed strong HDAC6 inhibitory potency and selectivity, on-target biological activity, and a safe therapeutic window in nontransformed cell lines. In primary T-PLL patient cells, where
Identifiants
pubmed: 34101461
doi: 10.1021/acs.jmedchem.1c00420
pmc: PMC8237267
doi:
Substances chimiques
Antineoplastic Agents
0
Bridged Bicyclo Compounds, Heterocyclic
0
Histone Deacetylase Inhibitors
0
Hydroxamic Acids
0
Pyrrolidines
0
RG7388
0
Sulfonamides
0
para-Aminobenzoates
0
Bendamustine Hydrochloride
981Y8SX18M
HDAC6 protein, human
EC 3.5.1.98
Histone Deacetylase 6
EC 3.5.1.98
venetoclax
N54AIC43PW
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
8486-8509Subventions
Organisme : Austrian Science Fund FWF
ID : I 4157
Pays : Austria
Organisme : Austrian Science Fund FWF
ID : I 4218
Pays : Austria
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