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）
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 40%PEG300 5%Tween80 50%ddH2O

この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。

 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. 
* <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. 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.[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 this compound 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. This compound 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.

参考

  • https://pubmed.ncbi.nlm.nih.gov/18256683/
  • https://pubmed.ncbi.nlm.nih.gov/32550904/

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：

HSD17B4 deficiency causes dysregulation of primary cilia and is alleviated by acetyl-CoA [ Nat Commun, 2025, 16(1):2663] PubMed: 40102401
Hypoxia-induced conversion of sensory Schwann cells into repair cells is regulated by HDAC8 [ Nat Commun, 2025, 16(1):515] PubMed: 39779705
Binding mechanism and distant regulation of histone deacetylase 8 by PCI-34051 [ Commun Biol, 2025, 8(1):221] PubMed: 39939814
Inhibition of HDAC6 elicits anticancer effects on head and neck cancer cells through Sp1/SOD3/MKP1 signaling axis to downregulate ERK phosphorylation [ Cell Signal, 2025, 127:111587] PubMed: 39755348
Collagen signaling and matrix stiffness regulate multipotency in glandular epithelial stem cells in mice [ Nat Commun, 2024, 15(1):10482] PubMed: 39695111
Inhibition of HDAC8 mitigates AKI by reducing DNA damage and promoting homologous recombination repair [ J Cell Mol Med, 2024, 28(18):e70114] PubMed: 39317961
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
Establishing a Drug Screening Platform for Polycystic Kidney Disease in Kidney Organoids [ The University of Auckland, 2023, ] PubMed: none
Histone Deacetylase 8 Is a Novel Therapeutic Target for Mantle Cell Lymphoma and Preserves Natural Killer Cell Cytotoxic Function [ Digital Commons University of South Florida, 2023, ] PubMed: None

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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