PCI-34051 --- HDAC8 Inhibitor

PCI-34051 is a potent and selective inhibitor of histone deacetylase 8 (HDAC8) with an IC50 ~10 nM. It displays >200 fold selectivity over other HDAC isoforms 1, 2, 3, 6 and 10. PCI-34051 has a unique mechanism of action involving PLCgamma1 activation and calcium-induced apoptosis, and could offer benefits including a greater therapeutic index for treating T-cell malignancies. PCI-34051 induces caspase-dependent apoptosis in cell lines derived from T-cell lymphomas or leukemia, but not in other hematopoietic or solid tumor lines. Unlike broad-spectrum HDAC inhibitors, PCI-34051 does not cause detectable histone or tubulin acetylation. Cells defective in T-cell receptor signaling were still sensitive to PCI-34051-induced apoptosis, whereas a phospholipase C-gamma1 (PLCgamma1)-defective line was resistant. In addition, steady-state calcium levels strongly influence the apoptosis induced by PCI-34051. It also induces cytochrome c release from mitochondria.

Product information

CAS Number: 950762-95-5

Molecular Weight: 296.32

Formula: C17H16N2O3

Chemical Name: N-hydroxy-1-(4-methoxybenzyl)-1H-indole-6-carboxamide

Smiles: COC1C=CC(CN2C=CC3=CC=C(C=C23)C(=O)NO)=CC=1

InChiKey: AJRGHIGYPXNABY-UHFFFAOYSA-N

InChi: 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)

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO up to 100 mM

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

PCI-34051 was used at 5 µM final concentration in various in vitro assays.

References:

1. Balasubramanian S, et al. A novel histone deacetylase 8 (HDAC8)-specific inhibitor PCI-34051 induces apoptosis in T-cell lymphomas. (2008) Leukemia. 22(5):1026-34.
2. Pipalia NH, et al. Histone deacetylase inhibitor treatment dramatically reduces cholesterol accumulation in Niemann-Pick type C1 mutant human fibroblasts. (2011) Proc Natl Acad Sci USA. 108(14):5620-5.

Products are for research use only. Not for human use.

Documents