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@ARTICLE{Chen:282518,
author = {X. Chen and J. Wang and P. Zhao and B. Dang and T. Liang
and R. Steimbach$^*$ and A. Miller$^*$ and J. Liu and X.
Wang and T. Zhang and X. Luan and J. Hu and J. Gao},
title = {{T}etrahydro-β-carboline derivatives as potent histone
deacetylase 6 inhibitors with broad-spectrum
antiproliferative activity.},
journal = {European journal of medicinal chemistry},
volume = {260},
issn = {0009-4374},
address = {Amsterdam [u.a.]},
publisher = {Elsevier Science},
reportid = {DKFZ-2023-01807},
pages = {115776},
year = {2023},
abstract = {A series of tetrahydro-β-carboline (THβC)-based
hydroxamic acids were rationally designed and synthesized as
novel selective HDAC6 inhibitors (sHDAC6is) by the
application of scaffold hopping strategy. Several THβC
analogues were highly potent (IC50 < 5 nM) and selective
against HDAC6 enzyme and exhibited good antiproliferative
activity against human multiple myeloma (MM) cell. Molecular
docking interpreted the structure activity relationship
(SAR). Target engagement of HDAC6 was confirmed in RPMI-8226
cells using the WB assay. In vitro, (1S,
3R)-1-(4-chlorophenyl)-N-(4-(hydroxycarbamoyl)benzyl)-2,3,4,9-tetrahydro-1H-pyrido[3,
4-b]indole-3-carboxamide (14g) showed potent broad
antiproliferative activity against various tumors including
leukemia, colon cancer, melanoma, and breast cancer cell
lines, better than ACY-1215. Moreover, 14g also showed good
pharmacokinetics properties in mice via oral
administration.},
keywords = {Antiproliferative (Other) / HDAC6 inhibitor (Other) /
Selectivity (Other) / Synthesis (Other) / THβC (Other)},
cin = {A390 / HD01},
ddc = {610},
cid = {I:(DE-He78)A390-20160331 / I:(DE-He78)HD01-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37660484},
doi = {10.1016/j.ejmech.2023.115776},
url = {https://inrepo02.dkfz.de/record/282518},
}