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Drug-Target Interaction

Drug

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PubChem ID:5311
Structure:
Synonyms:
149647-78-9
1zz1
4-Dimethylamino-N-(6-hydroxycarbamoylhexyl)benzamide
AC-1923
AC1L1K2K
AIDS-186714
AIDS186714
BRD-K81418486-001-10-3
C111237
CCRIS 8456
CHEBI:45716
CHEMBL98
D06320
DB02546
EC-000.2057
FT-0082592
HMS2219L20
HMS3264D20
LS-186548
LS-186997
LS-187780
M344
M344 compound
MK-0683
MK0683
MLS001065855
N'-hydroxy-N-phenyloctanediamide
N-Hydroxy-7-(4-dimethylaminobenzoyl)aminoheptanamide
N-Hydroxy-N'-phenyl octanediamide
N-hydroxy-N'-phenyl-octane-1,8-diotic acid diamide
N-hydroxy-N'-phenyloctanediamide
N-Hyrdroxy-N'-phenyloctanediamide
N1-hydroxy-N8-phenyloctanediamide
NCGC00168085-01
NCGC00168085-02
NCGC00168085-03
NCGC00168085-04
nchembio.275-comp2
nchembio.313-comp1
nchembio815-comp18
NHNPODA
NSC-701852
NSC701852
Octanediamide, N-hydroxy-N'-phenyl-
OCTANEDIOIC ACID HYDROXYAMIDE PHENYLAMIDE
P111011
S1047_Selleck
SAHA
SAHA cpd
SAHA, Suberoylanilide hydroxamic acid
SHH
SKI390
SMR000486344
Suberanilohydroxamic acid
Suberoylanilide hydroxamic acid
Suberoylanilide hydroxamic acid (SAHA)
SW-064652
UNII-58IFB293JI
Vorinostat
Vorinostat (JAN/USAN)
Vorinostat (USAN)
Vorinostat MSD
Vorinostat [USAN]
Vorinostat-Supplied by Selleck Chemicals
WIN64652
ZINC01543873
Zolinza
Zolinza (TN)
Zolinza, MK-0683, SAHA
ATC-Codes:

Target

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Uniprot ID:Q6RVA0_HUMAN
Synonyms:
P-glycoprotein
EC-Numbers:-
Organism:Homo sapiens
Human
PDB IDs:-

Binding Affinities:

Ki: Kd:Ic 50:Ec50/Ic50:
----

References:

12907619
Novel mechanisms of apoptosis induced by histone deacetylase inhibitors.. Melissa J Peart; Kellie M Tainton; Astrid A Ruefli; Anthony E Dear; Karin A Sedelies; Lorraine A O'Reilly; Nigel J Waterhouse; Joseph A Trapani; Ricky W Johnstone (2003) Cancer research display abstract
Histone deacetylase inhibitors (HDACIs) are a new class of chemotherapeutic drugs able to induce tumor cell apoptosis and/or cell cycle arrest; however, the molecular mechanisms underpinning their anticancer effects are poorly understood. Herein, we assessed the apoptotic pathways activated by three HDACIs, suberoylanilide hydroxamic acid, oxamflatin, and depsipeptide. We determined that all three drugs induced the accumulation of cells with a 4n DNA content and apoptosis mediated by the intrinsic apoptotic pathway. HDACI-induced mitochondrial membrane damage and apoptosis were inhibited by overexpression of Bcl-2, but not by the polycaspase inhibitor N-tert-butoxy-carbonyl-Val-Ala-Asp-fluoromethylketone (zVAD-fmk). Moreover, induction of a G(1)-S checkpoint through overexpression of p16(INK4A) or suppression of de novo protein synthesis also inhibited HDACI-induced cell death. Proteolytic cleavage of caspase-2, which is poorly inhibited by zVAD-fmk, was concomitant with HDACI-induced death; however, full processing of caspase-2 to the p19 active form was blocked by Bcl-2. Whereas all three drugs induce the activation of the proapoptotic Bcl-2 protein Bid upstream of mitochondrial membrane disruption, Bid cleavage in response to depsipeptide was significantly attenuated by zVAD-fmk. Suberoylanilide hydroxamic acid and oxamflatin could kill both P-glycoprotein (P-gp)(+) MDR cells and their P-gp(-) counterparts, whereas depsipeptide was shown to be a substrate for P-gp and was less effective in killing P-gp(+) cells. These data provide insight into the functional profile of three HDACIs and are important for the development of more rational approaches to chemotherapy, where information regarding the genetic profile of the tumor is matched with the functional profile of a given chemotherapeutic drug to promote favorable clinical responses.