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PCI-34051 HDAC8 Inhibidor

Name: PCI-34051
Brand: Selleck Chemicals
SKU: S2012
Rating: 5 (56 reviews)

Cat. No.: S2012

PCI-34051 es un potente y específico inhibidor de HDAC8 con una IC50 de 10 nM en un ensayo sin células. Presenta una selectividad superior a 200 veces sobre HDAC1 y 6, y más de 1000 veces sobre HDAC2, 3 y 10. PCI-34051 induce la apoptosis dependiente de caspasa.

PCI-34051 HDAC Inhibidor Chemical Structure

Estructura química

Peso molecular: 296.32

Saltar a

Control de calidad (Quality Control)

Lote: Pureza: 99.79%

99.79

Dianas relacionadas	JAK BET Histone Methyltransferase PKC PARP HIF PRMT EZH2 AMPK Sirtuin
Otros HDAC Inhibidores	ITF-2357 (Givinostat) Hydrochloride Monohydrate Fimepinostat (CUDC-907) Trichostatin A (TSA) Entinostat (MS-275) RGFP966 Quisinostat (JNJ-26481585) Dihydrochloride Tubastatin A Hydrochloride Tubastatin A Mocetinostat (MGCD0103) Ricolinostat (ACY-1215)

Cultivo celular, tratamiento y concentración de trabajo
(Cell Culture, Treatment & Working Concentration)

Líneas celulares	Tipo de ensayo	Concentración	Tiempo de incubación	Descripción de la actividad	PMID
LAN1	Growth inhibition assay		72 hrs	Growth inhibition of human LAN1 cells incubated for 72 hrs by MTS assay, GI50=3.9μM	23116147
Jurkat	Growth inhibition assay		72 hrs	Growth inhibition of human Jurkat cells incubated for 72 hrs by MTS assay, GI50=11μM	23116147
NB-1	Growth inhibition assay		72 hrs	Growth inhibition of human NB-1 cells incubated for 72 hrs by MTS assay, GI50=14μM	23116147
MT2	Growth inhibition assay		72 hrs	Growth inhibition of human MT2 cells incubated for 72 hrs by MTS assay, GI50=15μM	23116147
MT4	Growth inhibition assay		72 hrs	Growth inhibition of human MT4 cells incubated for 72 hrs by MTS assay, GI50=25μM	23116147
Huh7	Antiviral assay		3 days	Antiviral activity against HCV genotype 1b infected in human Huh7 cells after 3 days by luciferase reporter gene assay, EC50=1.8μM	25490700
HuH7	Cytotoxicity assay		3 days	Cytotoxicity against human HuH7 cells assessed as inhibition of cell viability after 3 days by CellTiter 96 assay, CC50=11μM	25490700
Sf9	Function assay		5 mins	Inhibition of recombinant full-length human C-terminal FLAG-His-tagged HDAC1 expressed in baculovirus infected Sf9 insect cells using Boc-L-Lys(Ac)-AMC as substrate preincubated for 5 mins followed by substrate addition measured after 35 mins by fluoresce, IC50=3.8μM	28835796
Sf9	Function assay		5 mins	Inhibition of recombinant human full-length C-terminal His-tagged HDAC3 (395 to 489 residues)/human NCOR2 expressed in baculovirus infected Sf9 insect cells using Boc-L-Lys(Ac)-AMC as substrate pretreated for 5 mins followed by substrate addition measured, IC50=7.1μM	28835796
Sf9	Function assay		5 mins	Inhibition of recombinant human full-length C-terminal His-tagged HDAC2 expressed in baculovirus infected Sf9 insect cells using Boc-L-Lys(Ac)-AMC as substrate preincubated for 5 mins followed by substrate addition measured after 35 mins by fluorescence assay, IC50=31μM	28835796
SH-SY5Y	Cytotoxicity assay			Cytotoxicity against human SH-SY5Y cells expressing TP53 by CellTiter96 AQueous one solution cell proliferation assay	28835796
IMR5	Cytotoxicity assay			Cytotoxicity against human IMR5 cells expressing TP53 by CellTiter96 AQueous one solution cell proliferation assay	28835796
SK-N-AS	Cytotoxicity assay			Cytotoxicity against human SK-N-AS cells expressing TP53 mutation by CellTiter96 AQueous one solution cell proliferation assay	28835796
Kelly	Cytotoxicity assay			Cytotoxicity against human Kelly cells expressing TP53 mutation by CellTiter96 AQueous one solution cell proliferation assay	28835796
BE(2)-C	Cytotoxicity assay		72 hrs	Cytotoxicity against human BE(2)-C cells assessed as reduction in cell viability by measuring metabolic activity after 72 hrs by WST-8 assay, IC50=19.9μM	29190092
Sf9	Function assay		90 mins	Inhibition of recombinant human full length C-terminal FLAG-tagged HDAC1 expressed in fall armyworm Sf9 cells using fluorogenic ZMAL as substrate after 90 mins by fluorimetric analysis, IC50=28.3μM	29190092
Sf9	Function assay		90 mins	Inhibition of recombinant human full length HDAC6 expressed in fall armyworm Sf9 cells using fluorogenic ZMAL as substrate after 90 mins by fluorimetric analysis, IC50=48.2μM	29190092
BE(2)-C	Function assay	6 uM	72 hrs	Inhibition of HDAC8 in human BE(2)-C cells assessed as upregulation of p21/CDKN1 gene expression at 6 uM after 72 hrs by RT-PCR analysis relative to control	29190092
BE(2)-C	Function assay	6 uM	72 hrs	Inhibition of HDAC8 in human BE(2)-C cells assessed as upregulation of TrkA/NTRK1 gene expression at 6 uM after 72 hrs by RT-PCR analysis relative to control	29190092
BE(2)-C	Function assay	6 uM	72 hrs	Inhibition of HDAC8 in human BE(2)-C cells assessed as upregulation of TH gene expression at 6 uM after 72 hrs by RT-PCR analysis relative to control	29190092
BE(2)-C	Function assay	6 uM	6 days	Induction of outgrowth of neurofilament positive neutrite-like structures in human BE(2)-C cells at 6 uM after 6 days by DAPI-staining based microscopic analysis	29190092
A673	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
SK-N-MC	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
NB-EBc1	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
SK-N-SH	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	29435139
NB1643	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	29435139
LAN-5	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
Jurkat	Antiproliferative assay			Antiproliferative activity against human Jurkat cells by alamar blue assay, GI50=2.4μM	29505935
HUT78	Antiproliferative assay			Antiproliferative activity against human HUT78 cells by alamar blue assay, GI50=2.4μM	29505935
HSB2	Antiproliferative assay			Antiproliferative activity against human HSB2 cells by alamar blue assay, GI50=2.4μM	29505935
MOLT4	Antiproliferative assay			Antiproliferative activity against human MOLT4 cells by alamar blue assay, GI50=2.4μM	29505935
Jurkat	Antiproliferative assay		48 hrs	Antiproliferative activity against human Jurkat cells after 48 hrs by MTT assay, IC50=4.5μM	29533873
MOLT4	Antiproliferative assay		48 hrs	Antiproliferative activity against human MOLT4 cells after 48 hrs by MTT assay, IC50=9.4μM	29533873
HEL	Antiproliferative assay		48 hrs	Antiproliferative activity against human HEL cells after 48 hrs by MTT assay, IC50=10.8μM	29533873
SK-N-BE(2)	Antiproliferative assay		48 hrs	Antiproliferative activity against human SK-N-BE(2) cells after 48 hrs by MTT assay, IC50=16.9μM	29533873
PC3	Antiproliferative assay		48 hrs	Antiproliferative activity against human PC3 cells after 48 hrs by MTT assay, IC50=19.2μM	29533873
K562	Antiproliferative assay		72 hrs	Antiproliferative activity against human K562 cells after 72 hrs by MTS assay, GI50=2.01μM	30004697
K562R	Antiproliferative assay		72 hrs	Antiproliferative activity against human K562R cells after 72 hrs by MTS assay, GI50=2.2μM	30004697
HCT116	Antiproliferative assay		72 hrs	Antiproliferative activity against human HCT116 cells after 72 hrs by MTS assay, GI50=2.64μM	30004697
PC3	Antiproliferative assay		72 hrs	Antiproliferative activity against human PC3 cells after 72 hrs by MTS assay, GI50=2.66μM	30004697
MCF7	Antiproliferative assay		72 hrs	Antiproliferative activity against human MCF7 cells after 72 hrs by MTS assay, GI50=2.97μM	30004697
BL21 (DE3)	Function assay			Binding affinity to human His-thioredoxin-tagged HDAC8 expressed in Escherichia coli BL21 (DE3) cells by ITC method, Kd=0.0751μM	30347148
BL21 (DE3)	Function assay			Inhibition of human His-thioredoxin-tagged HDAC8 expressed in Escherichia coli BL21 (DE3) cells using Fluor de Lys (R)-HDAC8 as substrate by fluorometric method, IC50=0.0777μM	30347148
BL21 (DE3)	Function assay			Binding affinity to Schistosoma mansoni His-tagged HDAC8 expressed in Escherichia coli BL21 (DE3) cells by ITC method, Kd=0.367μM	30347148
BL21 (DE3)	Function assay			Inhibition of Schistosoma mansoni His-tagged HDAC8 expressed in Escherichia coli BL21 (DE3) cells using Fluor de Lys (R)-HDAC8 as substrate by fluorometric method, IC50=0.4358μM	30347148
BL21 (DE3)	Function assay			Inhibition of human His-thioredoxin-tagged HDAC8 mL6/L179I mutant expressed in Escherichia coli BL21 (DE3) cells using Fluor de Lys (R)-HDAC8 as substrate by fluorometric method, IC50=1μM	30347148
BL21 (DE3)	Function assay			Inhibition of human His-thioredoxin-tagged HDAC8 mL6 mutant expressed in Escherichia coli BL21 (DE3) cells using Fluor de Lys (R)-HDAC8 as substrate by fluorometric method, IC50=1.63μM	30347148
BL21 (DE3)	Function assay			Inhibition of human His-thioredoxin-tagged HDAC8 mL1/mL6 mutant expressed in Escherichia coli BL21 (DE3) cells using Fluor de Lys (R)-HDAC8 as substrate by fluorometric method, IC50=2.7μM	30347148
BL21 (DE3)	Function assay			Inhibition of human His-thioredoxin-tagged HDAC8 mL1/mL6/L179I mutant expressed in Escherichia coli BL21 (DE3) cells using Fluor de Lys (R)-HDAC8 as substrate by fluorometric method, IC50=5μM	30347148
Sf9	Function assay			Inhibition of C-terminal FLAG/His-tagged full length human HDAC1 expressed in baculovirus infected Sf9 insect cells using Z(Ac)Lys-AMC as substrate by fluorometric method, IC50=28.3μM	30347148
Sf9	Function assay			Inhibition of N-terminal GST-tagged full length human HDAC6 expressed in baculovirus infected Sf9 insect cells using Z(Ac)Lys-AMC as substrate by fluorometric method, IC50=48.2μM	30347148
Sf9	Function assay		40 mins	Inhibition of recombinant human full length C-terminal His-tagged HDAC8 expressed in baculovirus infected insect cells measured after 40 mins by HDAC-Glo1/2 luminescent assay, IC50=0.03162μM	30964290
SK-N-BE(2)C	Anticlonogenic assay		96 hrs	Anticlonogenic activity in human SK-N-BE(2)C cells assessed as reduction in cell proliferation incubated for 96 hrs by crystal violet staining based assay, GI50=15μM	31630054
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Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Peso molecular	296.32	Fórmula	C₁₇H₁₆N₂O₃	Almacenamiento (Desde la fecha de recepción)	3 años-20°Cpolvo
Nº CAS	950762-95-5	Descargar SDF		Almacenamiento de soluciones madre	1 año-80°Cen disolvente 1 mes-20°Cen disolvente
Sinónimos	N/A			Smiles	COC1=CC=C(C=C1)CN2C=CC3=C2C=C(C=C3)C(=O)NO

Solubilidad (Solubility)

In vitro
Lote:

DMSO : 59 mg/mL (199.1 mM)
(El DMSO contaminado con humedad puede reducir la solubilidad. Usar DMSO fresco y anhidro.)

Water : Insoluble

Ethanol : Insoluble

Calculadora de Molaridad

Masa	Concentración	Volumen	Peso molecular
=	×	×

Calculadora de Dilución Calculadora de Peso Molecular

In vivo Lote:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validado por los laboratorios Selleck. Si necesita ajustes en esta formulación, contacte con nuestro equipo de ventas para pruebas personalizadas.	5.000mg/ml (16.87mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

Calculadora de formulación in vivo (Solución clara)

Paso 1: Introduzca la información a continuación (Recomendado: Un animal adicional para tener en cuenta la pérdida durante el experimento)

Dosis: mg/kg Peso promedio de los animales: g Volumen de dosificación por animal:μL Número de animales:

Paso 2: Introduzca la formulación in vivo (Esto es solo la calculadora, no la formulación. Por favor, contáctenos primero si no hay una formulación in vivo en la sección de Solubilidad.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Resultados del cálculo:

Concentración de trabajo: mg/ml;

Método para preparar el líquido maestro de DMSO: mg fármaco predissuelto en μL DMSO ( Concentración del líquido maestro mg/mL, Por favor, contáctenos primero si la concentración excede la solubilidad del DMSO del lote del fármaco. )

Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadirμL PEG300, mezclar y clarificar, luego añadirμL Tween 80, mezclar y clarificar, luego añadir μL ddH₂O, mezclar y clarificar.

Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadir μL Aceite de maíz, mezclar y clarificar.

Nota: 1. Por favor, asegúrese de que el líquido esté claro antes de añadir el siguiente disolvente.
2. Asegúrese de añadir el (los) disolvente(s) en orden. Debe asegurarse de que la solución obtenida, en la adición anterior, sea una solución clara antes de proceder a añadir el siguiente disolvente. Se pueden utilizar métodos físicos como el vórtice, el ultrasonido o el baño de agua caliente para ayudar a la disolución.

Mecanismo de acción (Mechanism of Action)

Targets/IC₅₀/Ki	HDAC8 (Cell-free assay) 10 nM
In vitro	PCI-34051 possesses promising potency for HDAC8 with a K_i of 10 nM. This compound has high selectivity (approximately fivefold) for HDAC8 relative to the other class I HDACs including HDAC1. It reveals greater than 200-fold selectivity over HDAC1 and HDAC6, and greater than 1000-fold selectivity over HDAC2, HDAC3 and HDAC10. This chemical inhibits ovarian tumor line OVCAR-3 with a GI50 of 6 μM and 15% cell death. Neither significant tubulin nor histone acetylation is observed in the sensitive cell lines treated with this compound at concentrations less than 25 μM at 24 hours nor at earlier timepoints. It induces a selective cytotoxic effect in cell lines derived only from T-cell malignancies. This compound induces caspase-dependent apoptosis. When caspase-3 activity is measured at various times after treatment with 5 μM of this chemical, increasing levels of activity are observed from 12 to 24 to 48 hours, another hallmark of apoptosis, consistent with the higher levels of caspase activity at this timepoint. It does not stimulate Bid cleavage, a characteristic effect of the extrinsic apoptotic pathway. While P116 and J.RT3-T.5 are sensitive to this compound, the PLCγ1-deficient J.gamma1 line reveals a marked decrease in the extent of its induced apoptosis. In addition, steady-state calcium levels strongly influence the apoptosis induced by this chemical. It induces cytochrome c release from mitochondria.
Ensayo de quinasa	Actividad de histona desacetilasa
Ensayo de quinasa	Para la caracterización de PCI-34051, las mediciones se realizan en un volumen de reacción de 100 μL utilizando placas de ensayo de 96 pocillos en un lector de placas de fluorescencia. Para cada isoenzima. La proteína HDAC en tampón de reacción (50 mM HEPES, 100 mM KCl, 0,001% Tween-20, 5% dimetil sulfóxido, pH 7,4, suplementado con albúmina sérica bovina en concentraciones de 0-0,05%) se mezcla con este compuesto a varias concentraciones y se deja incubar durante 15 min. Se añade tripsina a una concentración final de 50 nM, y acetil-glicil-Ala-(N-acetil-Lis)-amino-4-metilcoumarina se añade a una concentración final de 25-100 μM para iniciar la reacción. Después de un tiempo de latencia de 30 min, la fluorescencia se mide durante un período de 30 min utilizando una longitud de onda de excitación de 335 nm y una longitud de onda de detección de 460 nm. El aumento de la fluorescencia con el tiempo se utiliza como medida de la velocidad de reacción.
In vivo	PCI-34051 is a potent and specific HDAC8 inhibitor.
Referencias	[1] https://pubmed.ncbi.nlm.nih.gov/18256683/ [2] https://pubmed.ncbi.nlm.nih.gov/32550904/

Aplicaciones (Applications)

Métodos	Biomarcadores	Imágenes	PMID
Immunofluorescence	SMC3 / Ac-SMC3		27072133

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):