PCI-34051

製品コードS2012 バッチS201204

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C17H16N2O3
分子量 296.32 CAS No. 950762-95-5
Solubility (25°C)* 体外 DMSO 59 mg/mL (199.1 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
5.0mg/ml 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. 
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 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.
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

PCI-34051 is a potent and specific HDAC8 inhibitor.

プロトコル(参考用のみ)

キナーゼアッセイ 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.
細胞アッセイ 細胞株 A549 cell line, Ovcar-3 cell line
濃度 5 μM
反応時間 24 hours
実験の流れ

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.
動物実験 動物モデル Male C57BL/6 and BALB/c mice
投薬量 40 mg/kg
投与方法 i.p.

カスタマーフィードバック

Data from [Data independently produced by , , Exp Mol Med, 2017, 49(2):e297]

Data from [Data independently produced by , , Stem Cells Transl Med, 2018, doi:10.1002/sctm.18-0057]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Aberrant expression of histone deacetylase 8 in endometriosis and its potential as a therapeutic target [ Reprod Med Biol, 2023, 22(1):e12531] PubMed: 37564680
Corroborating evidence for aberrant expression of histone deacetylase 8 in endometriosis [ Reprod Med Biol, 2023, 22(1):e12527] PubMed: 37476367
Corroborating evidence for aberrant expression of histone deacetylase 8 in endometriosis [ Reprod Med Biol, 2023, 10.1002/rmb2.12527] PubMed: 37476367
Histone deacetylase 8 regulates NF-κB-related inflammation in asthmatic mice through H3K9 acetylation [ Chin Med J (Engl), 2022, 135(17):2110-2112.] PubMed: 35170504
TOB1 attenuates IRF3-directed antiviral responses by recruiting HDAC8 to specifically suppress IFN-β expression [ Commun Biol, 2022, 5(1):943] PubMed: 36085336
Repression of the PRELP gene is relieved by histone deacetylase inhibitors through acetylation of histone H2B lysine 5 in bladder cancer [ Clin Epigenetics, 2022, 14(1):147] PubMed: 36371227
HDAC2 Is Involved in the Regulation of BRN3A in Melanocytes and Melanoma [ Int J Mol Sci, 2022, 23(2)849] PubMed: 35055045
Development of Human Adrenocortical Adenoma (HAA1) Cell Line from Zona Reticularis [ Int J Mol Sci, 2022, 24(1)584] PubMed: 36614027
Species-selective targeting of pathogens revealed by the atypical structure and active site of Trypanosoma cruzi histone deacetylase DAC2 [ Cell Rep, 2021, 37(12):110129] PubMed: 34936867
Histone Deacetylase 4 Controls Extracellular Matrix Production in Orbital Fibroblasts from Graves' Ophthalmopathy Patients [ Thyroid, 2021, 10.1089/thy.2020.0948] PubMed: 34235979

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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