WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406284
CAS#: 950762-95-5
Description: PCI-34051 is a potent, histone deacetylase 8 (HDAC8)-specific inhibitor with >200-fold selectivity over the other HDAC isoforms. PCI-34051 induces caspase-dependent apoptosis in cell lines derived from T-cell lymphomas or leukemias, but not in other hematopoietic or solid tumor lines. Unlike broad-spectrum HDAC inhibitors, PCI-34051 does not cause detectable histone or tubulin acetylation. PCI-34051 could offer benefits including a greater therapeutic index for treating T-cell malignancies.
MedKoo Cat#: 406284
Name: PCI-34051
CAS#: 950762-95-5
Chemical Formula: C17H16N2O3
Exact Mass: 296.1161
Molecular Weight: 296.32
Elemental Analysis: C, 68.91; H, 5.44; N, 9.45; O, 16.20
Synonym: PCI34051; PCI 34051; PCI-34051
IUPAC/Chemical Name: N-hydroxy-1-(4-methoxybenzyl)-1H-indole-6-carboxamide
InChi Key: AJRGHIGYPXNABY-UHFFFAOYSA-N
InChi Code: InChI=1S/C17H16N2O3/c1-22-15-6-2-12(3-7-15)11-19-9-8-13-4-5-14(10-16(13)19)17(20)18-21/h2-10,21H,11H2,1H3,(H,18,20)
SMILES Code: O=C(C1=CC2=C(C=C1)C=CN2CC3=CC=C(OC)C=C3)NO
Appearance: White to gray solid powder
Purity: >97% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | PCI-34051 is a potent and selective HDAC8 inhibitor with IC50 of 10 nM |
| In vitro activity: | To refine the understanding of which HDACs are relevant in oxidative stress-induced neurodegeneration, an in vitro model of neuronal oxidative death was established. To investigate the role of HDAC8 in oxidative stress-induced neuronal death directly, HDAC8 gene expression was reduced using RNA interference. PCI-34051 was able to significantly protect the cells even when HDAC8 levels were reduced, suggesting that PCI-34051's neuroprotective effect is independent from HDAC8 inhibition. To rule out that the neuroprotective effect of PCI-34051 is dependent on its ability to inhibit residual HDAC8 activity in the knockdown cells, it was reasoned that, if PCI-34051 mediates neuroprotection by inhibiting residual HDAC8 activity in the HDAC8 knockdown cells, then it would be expected to observe that lower doses of PCI-34051 significantly mediate neuroprotection in HDAC8 knockdown cells compared with wild-type cells. Indeed, no changes were observed in the PCI-34051 neuroprotective dose–response, suggesting that the compound's neuroprotective effect is independent from inhibition of residual HDAC8 activity J Neurosci. 2014 Oct 22; 34(43): 14328–14337. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4205555/ |
| In vivo activity: | This study was to investigate the effects of HDAC8 inhibitor PCI-34051 on OVA-exposed lungs and IL-4 treated macrophages Mice were sensitized and then treated with budesonide (BUD) or PCI-34051 (PCI) prior to exposing to normal saline (NS) or ovalbumin (OVA). AHR and airway allergic inflammation were measured in mice exposed to either NS or OVA in presence and absence of BUD or PCI-34051, respectively. The ranking for the resistance measured from concentration-response curves was shown in such an order of OVA > PCI-34051 = BUD > NS in the airflow changes form the investigated animals. In contrast, the average value of Penn from OVA-challenged mice was a three-fold higher than the control mice at the highest dose of MCh (Fig.1a). Although treatment with BUD and PIC resulted in obvious decreases in airway resistance in the animals exposed to OVA, the values were still higher than the control. In statistical analysis, there were significant differences in the values measured at the dosage levels (12.5, 25 and 50 mg/ml) of MCh inhalation between OVA group and other groups (all P < 0.01, n = 6). Additionally, there were differences seen in the Penh values at the maximum dose of MCh challenge between NS-treated mice and BUD- or PCI-treated ones (P < 0.05, n = 6). In histopathological examination, representative images of lung sections showed more severe infiltration of peribronchial inflammatory cells and a large amount of mucus secretion in the OVA-exposed lungs than the NS-treated lungs. Treatment with BUD and PCI34051 resulted in significant reduction in the cell infiltration and mucus accumulation in the challenged lungs (Fig.11d). Respir Res. 2020; 21: 62. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048058/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 30.0 | 101.2 |
The following data is based on the product molecular weight 296.32 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1.Ha SD, Han CY, Reid C, Kim SO. HDAC8-mediated epigenetic reprogramming plays a key role in resistance to anthrax lethal toxin-induced pyroptosis in macrophages. J Immunol. 2014 Aug 1;193(3):1333-43. doi: 10.4049/jimmunol.1400420. Epub 2014 Jun 27. PMID: 24973453; PMCID: PMC4108443. 2. Sleiman SF, Olson DE, Bourassa MW, Karuppagounder SS, Zhang YL, Gale J, Wagner FF, Basso M, Coppola G, Pinto JT, Holson EB, Ratan RR. Hydroxamic acid-based histone deacetylase (HDAC) inhibitors can mediate neuroprotection independent of HDAC inhibition. J Neurosci. 2014 Oct 22;34(43):14328-37. doi: 10.1523/JNEUROSCI.1010-14.2014. Erratum in: J Neurosci. 2015 Jan 7;35(1):438. PMID: 25339746; PMCID: PMC4205555. 3. Rettig I, Koeneke E, Trippel F, Mueller WC, Burhenne J, Kopp-Schneider A, Fabian J, Schober A, Fernekorn U, von Deimling A, Deubzer HE, Milde T, Witt O, Oehme I. Selective inhibition of HDAC8 decreases neuroblastoma growth in vitro and in vivo and enhances retinoic acid-mediated differentiation. Cell Death Dis. 2015 Feb 19;6(2):e1657. doi: 10.1038/cddis.2015.24. PMID: 25695609; PMCID: PMC4669789. 4. Li ML, Su XM, Ren Y, Zhao X, Kong LF, Kang J. HDAC8 inhibitor attenuates airway responses to antigen stimulus through synchronously suppressing galectin-3 expression and reducing macrophage-2 polarization. Respir Res. 2020 Feb 28;21(1):62. doi: 10.1186/s12931-020-1322-5. PMID: 32111211; PMCID: PMC7048058. |
| In vitro protocol: | 1.Ha SD, Han CY, Reid C, Kim SO. HDAC8-mediated epigenetic reprogramming plays a key role in resistance to anthrax lethal toxin-induced pyroptosis in macrophages. J Immunol. 2014 Aug 1;193(3):1333-43. doi: 10.4049/jimmunol.1400420. Epub 2014 Jun 27. PMID: 24973453; PMCID: PMC4108443. 2. Sleiman SF, Olson DE, Bourassa MW, Karuppagounder SS, Zhang YL, Gale J, Wagner FF, Basso M, Coppola G, Pinto JT, Holson EB, Ratan RR. Hydroxamic acid-based histone deacetylase (HDAC) inhibitors can mediate neuroprotection independent of HDAC inhibition. J Neurosci. 2014 Oct 22;34(43):14328-37. doi: 10.1523/JNEUROSCI.1010-14.2014. Erratum in: J Neurosci. 2015 Jan 7;35(1):438. PMID: 25339746; PMCID: PMC4205555. |
| In vivo protocol: | 1. Rettig I, Koeneke E, Trippel F, Mueller WC, Burhenne J, Kopp-Schneider A, Fabian J, Schober A, Fernekorn U, von Deimling A, Deubzer HE, Milde T, Witt O, Oehme I. Selective inhibition of HDAC8 decreases neuroblastoma growth in vitro and in vivo and enhances retinoic acid-mediated differentiation. Cell Death Dis. 2015 Feb 19;6(2):e1657. doi: 10.1038/cddis.2015.24. PMID: 25695609; PMCID: PMC4669789. 2. Li ML, Su XM, Ren Y, Zhao X, Kong LF, Kang J. HDAC8 inhibitor attenuates airway responses to antigen stimulus through synchronously suppressing galectin-3 expression and reducing macrophage-2 polarization. Respir Res. 2020 Feb 28;21(1):62. doi: 10.1186/s12931-020-1322-5. PMID: 32111211; PMCID: PMC7048058. |
1: Ha SD, Han CY, Reid C, Kim SO. HDAC8-Mediated Epigenetic Reprogramming Plays a Key Role in Resistance to Anthrax Lethal Toxin-Induced Pyroptosis in Macrophages. J Immunol. 2014 Aug 1;193(3):1333-43. doi: 10.4049/jimmunol.1400420. Epub 2014 Jun 27. PubMed PMID: 24973453; PubMed Central PMCID: PMC4108443.
2: Wang C, Eessalu TE, Barth VN, Mitch CH, Wagner FF, Hong Y, Neelamegam R, Schroeder FA, Holson EB, Haggarty SJ, Hooker JM. Design, synthesis, and evaluation of hydroxamic acid-based molecular probes for in vivo imaging of histone deacetylase (HDAC) in brain. Am J Nucl Med Mol Imaging. 2013 Dec 15;4(1):29-38. eCollection 2013. PubMed PMID: 24380043; PubMed Central PMCID: PMC3867727.
3: 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. doi: 10.1038/leu.2008.9. Epub 2008 Feb 7. PubMed PMID: 18256683.
