Home Epigenetics HDAC inhibitor - Apoptosis related activator PCI-34051 For research use only.

PCI-34051

PCI-34051 is a potent and specific HDAC8 inhibitor with IC50 of 10 nM in a cell-free assay. It has greater than 200-fold selectivity over HDAC1 and 6, more than 1000-fold selectivity over HDAC2, 3, and 10. PCI-34051 induces caspase-dependent apoptosis.

PCI-34051 Chemical Structure

PCI-34051 Chemical Structure

CAS No. 950762-95-5

Purity & Quality Control

PCI-34051 Related Products

Signaling Pathway

HDAC Signaling Pathways

HDAC Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description 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
Click to View More Cell Line Experimental Data

Biological Activity

Description PCI-34051 is a potent and specific HDAC8 inhibitor with IC50 of 10 nM in a cell-free assay. It has greater than 200-fold selectivity over HDAC1 and 6, more than 1000-fold selectivity over HDAC2, 3, and 10. PCI-34051 induces caspase-dependent apoptosis.
Targets
HDAC8 [1]
(Cell-free assay)
10 nM
In vitro
In vitro

PCI-34051 possesses promising potency for HDAC8 with a Ki of 10 nM. PCI-34051 has high selectivity (approximately fivefold) for HDAC8 relative to the other class I HDACs including HDAC1. PCI-34051 reveals greater than 200-fold selectivity over HDAC1 and HDAC6, and greater than 1000-fold selectivity over HDAC2, HDAC3 and HDAC10. PCI-34051 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 PCI-34051 at concentrations less than 25 μM at 24 hours nor at earlier timepoints. PCI-34051 induces a selective cytotoxic effect in cell lines derived only from T-cell malignancies. PCI-34051 induces caspase-dependent apoptosis. When caspase-3 activity is measured at various times after treatment with 5 μM PCI-34051, 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. PCI-34051 does not stimulate Bid cleavage, a characteristic effect of the extrinsic apoptotic pathway. While P116 and J.RT3-T.5 are sensitive to PCI-34051, the PLCγ1-deficient J.gamma1 line reveals a marked decrease in the extent of PCI-34051-induced apoptosis. In addition, steady-state calcium levels strongly influence the apoptosis induced by PCI-34051. PCI-34051 induces cytochrome c release from mitochondria.[1]
Kinase Assay Histone deacetylase activity
For PCI-34051 characterization, measurements are perfomed in a reaction volume of 100 μL using 96-well assay plates in a fluorescence plate reader. For each isozyme. The HDAC protein in reaction buffer (50 mM HEPES, 100 mM KCl, 0.001% Tween-20, 5% dimethyl sulfoxide, pH7.4, supplemented with bovine serum albumin at concentrations of 0-0.05%) is mixed with PCI-34051 at various concentrations and allowed to incubate for 15 min. Trysin is added to a final concentration of 50 nM, and acetyl-gly-Ala-(N-acetyl-Lys)-amino-4-methylcoumarin is added to a final concentration of 25-100 μM to initiate the reaction. After a 30 min lag time, the fluorescence is measured over a 30 min time frame using an excitation wavelength of 335 nm and a detection wavelength of 460 nm. The increase in fluorescence wih time is used as the measure of the reaction rate.
Cell Research Cell lines A549 cell line, Ovcar-3 cell line
Concentrations 5 μM
Incubation Time 24 hours
Method

Tumor cell lines and human umbilical vein endothelial cells are cultured for at least two doubling times, and growth is monitored at the end of PCI-34051 exposure using an Alamar Blue fluorometric cell proliferation assay as recommended by the manufacturer. PCI-34051 is assayed in triplicate wells in 96-well plates. The concentration required to inhibit cell growth by 50% (GI50) and 95% confidence intervals are estimated from nonlinear regression using a four-parameter logistic equation.
Experimental Result Images Methods Biomarkers Images PMID
Immunofluorescence SMC3 / Ac-SMC3 27072133
In Vivo
In vivo

PCI-34051 is a potent and specific HDAC8 inhibitor.
Animal Research Animal Models Male C57BL/6 and BALB/c mice
Dosages 40 mg/kg
Administration i.p.

Chemical Information & Solubility

Molecular Weight 296.32 Formula

C17H16N2O3
CAS No. 950762-95-5 SDF Download PCI-34051 SDF
Smiles COC1=CC=C(C=C1)CN2C=CC3=C2C=C(C=C3)C(=O)NO
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 59 mg/mL ( (199.1 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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