Structural and in Vivo Characterization of Tubastatin A, a
Widely Used Histone Deacetylase 6 Inhibitor

J 2020

Structural and in Vivo Characterization of Tubastatin A, a Widely Used Histone Deacetylase 6 Inhibitor

SHEN, Sida; Michal SVOBODA; Guangming ZHANG; Maria A CAVASIN; Lucia MOTLOVA et al.

Základní údaje

Originální název

Structural and in Vivo Characterization of Tubastatin A, a Widely Used Histone Deacetylase 6 Inhibitor

Autoři

SHEN, Sida; Michal SVOBODA; Guangming ZHANG; Maria A CAVASIN; Lucia MOTLOVA; Timothy A MCKINSEY; James H EUBANKS; Cyril BARINKA a Alan P KOZIKOWSKI

Vydání

ACS Medicinal Chemistry Letters, USA, American Chemical Society, 2020, 1948-5875

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30107 Medicinal chemistry

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.345

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:90043/20:00139209

Organizační jednotka

CIISB

Klíčová slova anglicky

HDAC selectivity; zinc-binding group; phenylhydroxamate; brain penetration; neurological disorders

Štítky

ne MU, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 28. 3. 2025 17:55, Mgr. Eva Dubská

Anotace

V originále

Tubastatin A, a tetrahydro-gamma-carboline-capped selective HDAC6 inhibitor (HDAC6i), was rationally designed 10 years ago, and has become the best investigated HDAC6i to date. It shows efficacy in various neurological disease animal models, as HDAC6 plays a crucial regulatory role in axonal transport deficits, protein aggregation, as well as oxidative stress. In this work, we provide new insights into this HDAC6i by investigating the molecular basis of its interactions with HDAC6 through X-ray crystallography, determining its functional capability to elevate the levels of acetylated atubulin in vitro and in vivo, correlating PK/PD profiles to determine effective doses in plasma and brain, and finally assessing its therapeutic potential toward psychiatric diseases through use of the SmartCube screening platform.

Návaznosti

90043, velká výzkumná infrastruktura

Název: CIISB

Citovat

SHEN, Sida; Michal SVOBODA; Guangming ZHANG; Maria A CAVASIN; Lucia MOTLOVA; Timothy A MCKINSEY; James H EUBANKS; Cyril BARINKA a Alan P KOZIKOWSKI. Structural and in Vivo Characterization of Tubastatin A, a Widely Used Histone Deacetylase 6 Inhibitor. ACS Medicinal Chemistry Letters. USA: American Chemical Society, 2020, roč. 11, č. 5, s. 706-712. ISSN 1948-5875. Dostupné z: https://doi.org/10.1021/acsmedchemlett.9b00560.

@article{2487299,
   author = {Shen, Sida and Svoboda, Michal and Zhang, Guangming and Cavasin, Maria A and Motlova, Lucia and McKinsey, Timothy A and Eubanks, James H and Barinka, Cyril and Kozikowski, Alan P},
   article_location = {USA},
   article_number = {5},
   doi = {https://doi.org/10.1021/acsmedchemlett.9b00560},
   keywords = {HDAC selectivity; zinc-binding group; phenylhydroxamate; brain penetration; neurological disorders},
   language = {eng},
   issn = {1948-5875},
   journal = {ACS Medicinal Chemistry Letters},
   title = {Structural and in Vivo Characterization of Tubastatin A, a Widely Used Histone Deacetylase 6 Inhibitor},
   url = {https://pubs.acs.org/doi/10.1021/acsmedchemlett.9b00560},
   volume = {11},
   year = {2020}
}

TY  - JOUR
ID  - 2487299
AU  - Shen, Sida - Svoboda, Michal - Zhang, Guangming - Cavasin, Maria A - Motlova, Lucia - McKinsey, Timothy A - Eubanks, James H - Barinka, Cyril - Kozikowski, Alan P
PY  - 2020
TI  - Structural and in Vivo Characterization of Tubastatin A, a Widely Used Histone Deacetylase 6 Inhibitor
JF  - ACS Medicinal Chemistry Letters
VL  - 11
IS  - 5
SP  - 706-712
EP  - 706-712
PB  - American Chemical Society
SN  - 19485875
KW  - HDAC selectivity
KW  - zinc-binding group
KW  - phenylhydroxamate
KW  - brain penetration
KW  - neurological disorders
UR  - https://pubs.acs.org/doi/10.1021/acsmedchemlett.9b00560
N2  - Tubastatin A, a tetrahydro-gamma-carboline-capped selective HDAC6 inhibitor (HDAC6i), was rationally designed 10 years ago, and has become the best investigated HDAC6i to date. It shows efficacy in various neurological disease animal models, as HDAC6 plays a crucial regulatory role in axonal transport deficits, protein aggregation, as well as oxidative stress. In this work, we provide new insights into this HDAC6i by investigating the molecular basis of its interactions with HDAC6 through X-ray crystallography, determining its functional capability to elevate the levels of acetylated atubulin in vitro and in vivo, correlating PK/PD profiles to determine effective doses in plasma and brain, and finally assessing its therapeutic potential toward psychiatric diseases through use of the SmartCube screening platform.
ER  -

SHEN, Sida; Michal SVOBODA; Guangming ZHANG; Maria A CAVASIN; Lucia MOTLOVA; Timothy A MCKINSEY; James H EUBANKS; Cyril BARINKA a Alan P KOZIKOWSKI. Structural and in Vivo Characterization of Tubastatin A, a Widely Used Histone Deacetylase 6 Inhibitor. \textit{ACS Medicinal Chemistry Letters}. USA: American Chemical Society, 2020, roč.~11, č.~5, s.~706-712. ISSN~1948-5875. Dostupné z: https://doi.org/10.1021/acsmedchemlett.9b00560.

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