PCI-34051 | CAS#950762-95-5 | HDAC8 Inhibitor

MedKoo Cat#: 406284 | Name: PCI-34051

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

PCI-34051

CAS#950762-95-5

Theoretical Analysis

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

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,350.00	Ready to ship

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Related CAS #

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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

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#T8Z12C21

QC Data

View QC data: current batch, Lot#T8Z12C21

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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	mg/mL	mM
Solubility
	DMSO	30.0	101.20

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

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:

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: Chen X, Ding X, Fang J, Mao C, Gong X, Zhang Y, Zhang N, Yan F, Lou Y, Chen Z, Ding W, Ma Z. Natural Derivatives of Selective HDAC8 Inhibitors with Potent in Vivo Antitumor Efficacy against Breast Cancer. J Med Chem. 2024 Aug 7. doi: 10.1021/acs.jmedchem.4c01438. Epub ahead of print. PMID: 39110628. 2: Xiao Y, Awasthee N, Liu Y, Meng C, He MY, Hale S, Karki R, Lin Z, Mosterio M, Garcia BA, Kridel R, Liao D, Zheng G. Discovery of a Highly Potent and Selective HDAC8 Degrader: Advancing the Functional Understanding and Therapeutic Potential of HDAC8. J Med Chem. 2024 Aug 8;67(15):12784-12806. doi: 10.1021/acs.jmedchem.4c00761. Epub 2024 Jul 1. PMID: 38949959. 3: Long K, Close DA, Johnston PA, Huryn DM. Replacement of the hydroxamic acid group in the selective HDAC8 inhibitor PCI-34051. Bioorg Med Chem Lett. 2024 Aug 1;108:129810. doi: 10.1016/j.bmcl.2024.129810. Epub 2024 May 22. PMID: 38782078; PMCID: PMC11212034. 4: Fukuda M, Fujita Y, Hino Y, Nakao M, Shirahige K, Yamashita T. Inhibition of HDAC8 Reduces the Proliferation of Adult Neural Stem Cells in the Subventricular Zone. Int J Mol Sci. 2024 Feb 22;25(5):2540. doi: 10.3390/ijms25052540. PMID: 38473789; PMCID: PMC10932134. 5: Şansaçar M, Sağır H, Gencer Akçok EB. Inhibition of PI3K-AKT-mTOR pathway and modulation of histone deacetylase enzymes reduce the growth of acute myeloid leukemia cells. Med Oncol. 2023 Dec 26;41(1):31. doi: 10.1007/s12032-023-02247-8. PMID: 38148433. 6: Islam R, Singh R. Curcumin and PCI-34051 combined treatment ameliorates inflammation and fibrosis by affecting MAP kinase pathway. Inflammopharmacology. 2023 Dec;31(6):3063-3079. doi: 10.1007/s10787-023-01371-1. Epub 2023 Nov 7. PMID: 37934384. 7: Toro TB, Skripnikova EV, Bornes KE, Zhang K, Watt TJ. Endogenous expression of inactive lysine deacetylases reveals deacetylation-dependent cellular mechanisms. PLoS One. 2023 Sep 18;18(9):e0291779. doi: 10.1371/journal.pone.0291779. PMID: 37721967; PMCID: PMC10506724. 8: Wang B, Tian P, Sun Q, Zhang H, Han L, Zhu B. A novel, effective machine learning-based RNA editing profile for predicting the prognosis of lower-grade gliomas. Heliyon. 2023 Jul 7;9(7):e18075. doi: 10.1016/j.heliyon.2023.e18075. PMID: 37483735; PMCID: PMC10362151. 9: Amin SA, Khatun S, Gayen S, Das S, Jha T. Are inhibitors of histone deacetylase 8 (HDAC8) effective in hematological cancers especially acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL)? Eur J Med Chem. 2023 Oct 5;258:115594. doi: 10.1016/j.ejmech.2023.115594. Epub 2023 Jun 25. PMID: 37429084. 10: Zhou X, Chen H, Shi Y, Li J, Ma X, Du L, Hu Y, Tao M, Zhong Q, Yan D, Zhuang S, Liu N. Histone deacetylase 8 inhibition prevents the progression of peritoneal fibrosis by counteracting the epithelial-mesenchymal transition and blockade of M2 macrophage polarization. Front Immunol. 2023 Feb 23;14:1137332. doi: 10.3389/fimmu.2023.1137332. PMID: 36911746; PMCID: PMC9995794. 11: Kim JY, Cho H, Yoo J, Kim GW, Jeon YH, Lee SW, Kwon SH. HDAC8 Deacetylates HIF-1α and Enhances Its Protein Stability to Promote Tumor Growth and Migration in Melanoma. Cancers (Basel). 2023 Feb 9;15(4):1123. doi: 10.3390/cancers15041123. PMID: 36831463; PMCID: PMC9953989. 12: Kim JY, Han SY, Yoo J, Kim GW, Jeon YH, Lee SW, Park J, Kwon SH. HDAC8-Selective Inhibition by PCI-34051 Enhances the Anticancer Effects of ACY-241 in Ovarian Cancer Cells. Int J Mol Sci. 2022 Aug 3;23(15):8645. doi: 10.3390/ijms23158645. PMID: 35955780; PMCID: PMC9369251. 13: Huang C, Shu Y, Zhu Y, Liu H, Wang X, Wen H, Liu J, Li W. Discovery of non- substrate, environmentally sensitive turn-on fluorescent probes for imaging HDAC8 in tumor cells and tissue slices. Bioorg Med Chem. 2022 Aug 15;68:116821. doi: 10.1016/j.bmc.2022.116821. Epub 2022 May 21. PMID: 35661851. 14: Long K, Vaughn Z, McDaniels MD, Joyasawal S, Przepiorski A, Parasky E, Sander V, Close D, Johnston PA, Davidson AJ, de Caestecker M, Hukriede NA, Huryn DM. Validation of HDAC8 Inhibitors as Drug Discovery Starting Points to Treat Acute Kidney Injury. ACS Pharmacol Transl Sci. 2022 Mar 16;5(4):207-215. doi: 10.1021/acsptsci.1c00243. PMID: 35434532; PMCID: PMC9003639. 15: Zhao T, Kee HJ, Kee SJ, Jeong MH. Hdac8 Inhibitor Alleviates Transverse Aortic Constriction-Induced Heart Failure in Mice by Downregulating Ace1. Oxid Med Cell Longev. 2022 Jan 27;2022:6227330. doi: 10.1155/2022/6227330. PMID: 35126818; PMCID: PMC8813277. 16: Heppt MV, Wessely A, Hornig E, Kammerbauer C, Graf SA, Besch R, French LE, Matthies A, Kuphal S, Kappelmann-Fenzl M, Bosserhoff AK, Berking C. HDAC2 Is Involved in the Regulation of BRN3A in Melanocytes and Melanoma. Int J Mol Sci. 2022 Jan 13;23(2):849. doi: 10.3390/ijms23020849. PMID: 35055045; PMCID: PMC8778714. 17: Bai SY, Li ML, Ren Y, Su XM. HDAC8-inhibitor PCI-34051-induced exosomes inhibit human bronchial smooth muscle cell proliferation via miR-381-3p mediated TGFB3. Pulm Pharmacol Ther. 2021 Dec;71:102096. doi: 10.1016/j.pupt.2021.102096. Epub 2021 Nov 2. PMID: 34740750. 18: Schmidt O, Nehls N, Prexler C, von Heyking K, Groll T, Pardon K, Garcia HD, Hensel T, Gürgen D, Henssen AG, Eggert A, Steiger K, Burdach S, Richter GHS. Class I histone deacetylases (HDAC) critically contribute to Ewing sarcoma pathogenesis. J Exp Clin Cancer Res. 2021 Oct 15;40(1):322. doi: 10.1186/s13046-021-02125-z. Erratum in: J Exp Clin Cancer Res. 2022 Jan 3;41(1):7. doi: 10.1186/s13046-021-02174-4. PMID: 34654445; PMCID: PMC8518288. 19: Yan Y, Huang C, Shu Y, Wen H, Shan C, Wang X, Liu J, Li W. An HDAC8-selective fluorescent probe for imaging in living tumor cell lines and tissue slices. Org Biomol Chem. 2021 Oct 6;19(38):8352-8366. doi: 10.1039/d1ob01367j. PMID: 34528053. 20: Pojani E, Barlocco D. Selective Inhibitors of Histone Deacetylase 10 (HDAC-10). Curr Med Chem. 2022;29(13):2306-2321. doi: 10.2174/0929867328666210901144658. PMID: 34468295.