Rac-Belinostat

SKU: orb1307324

Description

Belinostat (PX-105684) is a hydroxamic acid-based HDAC inhibitor with antineoplastic properties. It induces tumor cell apoptosis and differentiation while inhibiting angiogenesis, and has shown efficacy in sensitizing resistant cells in vitro and in vivo models of various cancers.

Research Area

Cell Biology, Epigenetics & Chromatin, Molecular Biology, Pharmacology & Drug Discovery

Key Properties

• CAS Number: 414864-00-9
• MW: 318.35
• Purity: 99.93% (May vary between batches)
• Formula: C₁₅H₁₄N₂O₄S
• SMILES: ONC(=O)\C=C\c1cccc(c1)S(=O)(=O)Nc1ccccc1
• Target: HDAC
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (6.28 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);Ethanol:< 1 mg/mL (insoluble or slightly soluble);DMSO:65 mg/mL (204.18 mM)

Bioactivity

• Target IC50:
  HDAC:27 nM|HDAC6:82 nM
• In Vivo:
  Belinostat exhibits low activity against A2780/cp70 and 2780AD cells, which are derived from A2780 cells resistant to doxorubicin and cisplatin. In ovarian cancer cell lines, Belinostat enhances microtubule acetylation. It inhibits tumor cell growth, including A2780, HCT116, HT29, WIL, CALU-3, MCF7, PC3, and HS852 cells (IC50: 0.2-0.66 μM), through acetylation of histones H3/H4 and PARP cleavage, thereby inducing apoptosis. Belinostat notably suppresses the growth of bladder cancer cells, particularly the 5637 cells, with an accumulation of cells in the G0-G1 phase, a decline in the S phase, and an increase in the G2-M phase. Its inhibitory effect on cell growth is independent of the multidrug-resistant phenotype, although the activity of docetaxel is significantly affected. Belinostat enhances the inhibitory activity of carboplatin or docetaxel on A2780 and OVCAR-3 cells. Within a TGF-β signaling-dependent mechanism, Belinostat activates protein kinase A and reduces survivin mRNA levels.
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• In Vitro:
  In bladder cells of mice, Belinostat induces the expression of p21WAF1, core HDAC, and genes essential for cellular communication. When administered to A2780 and A2780/cp70 xenografts, Belinostat at a dosage of 10 mg/kg significantly delays tumor growth without affecting the body weight of the animals. A higher dose of Belinostat (100 mg/kg) targeting A2780 xenografts alone achieves a tumor inhibition rate of 47%, demonstrating a dose-dependent effect. The combined treatment of Belinostat (100 mg/kg) and Carboplatin (40 mg/kg) extends the delay in tumor growth to 18.6-22.5 days. Moreover, when applied to mice carrying Bortezomib-resistant UMSCC-11A xenografts, the compound exhibits gastrointestinal toxicity. Importantly, the concomitant use of Bortezomib and Belinostat significantly suppresses tumor growth.
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• Cell Research:
  Tumor cell lines are seeded in 5 mL of medium at a density of 8 × 104 cells/25 cm2 flask and incubated for 48 hours. Cells are exposed to Belinostat (0.016 to 10 μM) for 24 hours. The medium is removed, and 1 mL of trypsin/EDTA is added to each flask. Once the cells have detached, 1 mL of medium is added, the cells are resuspended, and those from the control untreated flask are counted. Cells are diluted and plated into 6-cm Petri dishes (three per flask) at a density of 0.5-2× 103 cells/dish depending on the cell line. Cells from the drug-treated flasks are diluted and plated as for the control flasks. Dishes are incubated for 10–15 days at 37 °C. Cells are washed with PBS, fixed in methanol, and stained with crystal violet, and colonies that contained ≥50 cells counted. Sensitivity is expressed as the IC50 defined as the concentration of belinostat required to reduce the number of colonies to 50% of that of the control untreated cells.(Only for Reference)
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Belinostat, HDAC, NSC726630, NSC-726630, NSC 726630, Rac-Belinostat, PXD 101, PXD101, PXD-101, PX 105684, PX-105684, PX105684

Compound Identifiers

PubChem CID

6918638