PCI-34051
PCI-34051 is a potent, specific inhibitor of histone deacetylase 8 (HDAC8) with greater than 200-fold selectivity over the other HDAC isoforms, such as 1, 2, 3, 6 and 10. It induces caspase dependent apoptosis in cell lines derived from T-cell lymphomas or leukemias, but not in other hematopoietic or solid tumor lines. PCI-34051 does not cause detectable histone or tubulin acetylation and also does not inhibit growth or induce apoptosis in normal cells such as PBMCs or fibroblasts. Although a phospholipase C-gamma1 (PLCgamma1) defective line is resistant, cells defective in T-cell receptor signaling are still sensitive to PCI-34051 induced apoptosis.
References:
[1]. S Balasubramanian, J Ramos, W Luo, M Sirisawad, E Verner, J J Buggy. A novel histone deacetylase 8 (HDAC8)-specific inhibitor PCI-34051 induces apoptosis in T-cell lymphomas. Leukemia (2008) 22, 1026–1034.
[2]. Sriram Balasubramanian, Erik Verner, Joseph J. Buggy. Isoform-specific histone deacetylase inhibitors: The next step? Cancer Letters. Volume 280, Issue 2, 8 August 2009, Pages 211–221.
- 1. Joseph Boyle, Derick Chiappo, et al. "Aminocoumarin-based heme oxygenase activity fluorescence probe reveals novel aspects of HO-1 regulation." Research Square. 22 Nov, 2023.
- 2. Manna PR, Ramachandran S, et al. "Expression and Function of StAR in Cancerous and Non-Cancerous Human and Mouse Breast Tissues: New Insights into Diagnosis and Treatment of Hormone-Sensitive Breast Cancer." Int J Mol Sci 2023 Jan 01;24(1) PMID: 36614200
- 3. Yu X, Li H, et al. "Involvement of p53 acetylation in growth suppression of Cutaneous T-cell lymphomas induced by HDAC inhibition." J Invest Dermatol. 2020;S0022-202X(20)30214-1. PMID:32119867
- 4. Huang Y, Yang W, et al. "Droxinostat sensitizes human colon cancer cells to apoptotic cell death via induction of oxidative stress." Cell Mol Biol Lett. 2018 Jul 28;23:34. PMID:30065760
| Storage | Store at -20°C |
| M.Wt | 296.32 |
| Cas No. | 950762-95-5 |
| Formula | C17H16N2O3 |
| Synonyms | PCI34051, PCI 34051 |
| Solubility | insoluble in H2O; insoluble in EtOH; ≥14.8 mg/mL in DMSO |
| Chemical Name | N-hydroxy-1-[(4-methoxyphenyl)methyl]indole-6-carboxamide |
| SDF | Download SDF |
| Canonical SMILES | COC1=CC=C(C=C1)CN2C=CC3=C2C=C(C=C3)C(=O)NO |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Kinase experiment [1]: | |
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Histone deacetylase activity |
For PCI-34051 characterization, measurements were 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, pH 7.4, supplemented with bovine serum albumin at concentrations of 0 ~ 0.05%) was mixed with PCI-34051 at various concentrations and allowed to incubate for 15 mins. Trypsin was added to a final concentration of 50 nM, and acetyl-Gly-Ala-(N-acetyl-Lys)-amino-4-methylcoumarin was added to a final concentration of 25 ~ 100 μM to initiate the reaction. After a 30 min lag time, the fluorescence was 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 with time was used as the measure of the reaction rate. |
| Cell experiment [1]: | |
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Cell lines |
T-cell derived lines (Jurkat, HuT78, HSB-2 and Molt-4 cells) |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reaction Conditions |
5 μM; 2 days |
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Applications |
The HDAC8-selective inhibitor PCI-34051 was cytotoxic to T-cell derived lines. |
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References: [1]. Balasubramanian S, Ramos J, Luo W, Sirisawad M, Verner E, Buggy JJ. A novel histone deacetylase 8 (HDAC8)-specific inhibitor PCI-34051 induces apoptosis in T-cell lymphomas. Leukemia. 2008 May;22(5):1026-34. |
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| Description | PCI-34051 is a potent and specific inhibitor of HDAC8 with an IC50 value of 10 nM. | |||||
| Targets | HDAC8 | HDAC6 | HDAC1 | HDAC10 | HDAC2 | HDAC3 |
| IC50 | 10 nM | 2.9 μM | 4 μM | 13 μM | >50 μM | >50 μM |
Quality Control & MSDS
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Chemical structure
Related Biological Data
Related Biological Data
