PCI-34051

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Technical Data

Molecular Weight 296.32 Storage powder
Formula

C17H16N2O3

in solvent
CAS No. 950762-95-5 Synonyms N/A
Solubility (25°C) * In vitro DMSO 59 mg/mL (199.1 mM)
Water <1 mg/mL
Ethanol <1 mg/mL
In vivo 30% PEG400+0.5% Tween80+5% propylene glycol 30 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Name 1-(4-methoxybenzyl)-N-hydroxy-1H-indole-6-carboxamide

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.
Targets
HDAC8 [1]
(Cell-free assay)
HDAC6 [1]
(Cell-free assay)
HDAC1 [1]
(Cell-free assay)
HDAC10 [1]
(Cell-free assay)
HDAC2 [1]
(Cell-free assay)
10 nM 2.9 μM 4 μM 13 μM >50 μM
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]
In vivo
Features  

Protocol (Only for Reference)

Kinase Assay: [1]

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 Assay: [1]

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.
 

References

PCI-34051 has been referenced in 3 publications.

PLEASE KEEP THE PRODUCT UNDER -20°C FOR LONG-TERM STORAGE.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.

Specific storage and handling information for each product is indicated on the product datasheet. Most Selleck products are stable under the recommended conditions. Products are sometimes shipped at a temperature that differs from the recommended storage temperature. Short-term storage of many products are stable in the short-term at temperatures that differ from that required for long-term storage.
We ensure that the product is shipped under conditions that will maintain the quality of the reagents. Upon receipt of the product, follow the storage recommendations on the product data sheet.

Chemical Structure

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