Panobinostat (LBH589), 99.96%

Broad-Spectrum Histone Deacetylase (HDAC) Inhibitor with Potent Antitumor and Latency-Reversing Properties

Panobinostat (LBH589, NVP-LBH589) is a novel, potent, and broad-spectrum HDAC inhibitor with an IC₅₀ of 5 nM in cell-free assays. It effectively inhibits HDAC activity in MOLT-4 T-cell leukemia cells (IC₅₀ = 5 nM) and Reh pre-B leukemia cells (IC₅₀ = 20 nM). As a Phase 3 clinical candidate, Panobinostat exhibits pro-apoptotic and autophagy-inducing effects, disrupts HIV-1 latency, and shows broad-spectrum antitumor activity, especially in hematologic malignancies and small cell lung cancer (SCLC) models.

Mechanism of Action

Panobinostat functions as a tight-binding HDAC inhibitor, promoting acetylation of histone proteins and non-histone targets, leading to cell cycle arrest, apoptosis, and transcriptional modulation of oncogenic and DNA repair pathways.

In Vitro Activity

• Targets: HDACs in MOLT-4 and Reh cell lines
• Activity:
  • IC₅₀ = 5 nM (MOLT-4)
  • IC₅₀ = 20 nM (Reh)
• Effects:
  • Induces apoptosis and G2/M arrest
  • Increases histone H3/H4 acetylation (H3K9ac, H4K8ac, etc.)
  • Upregulates p21 and downregulates c-Myc
  • Elevates DNA repair and pro-apoptotic gene expression
  • Inhibits cell proliferation across multiple cancer cell lines (e.g., NSCLC, SCLC, mesothelioma)

Cell Research Protocol

In Vivo Efficacy

Panobinostat exhibits significant tumor suppression in vivo:

• Model: SCID mice xenografted with lung cancer or mesothelioma cells
• Dose: 20 mg/kg (i.p.), 5 days/week
• Results:
  • Up to 81% tumor volume reduction (BK-T, RG-1, H69)
  • Particularly effective against small cell lung cancer (SCLC) models
  • Comparable efficacy in immunocompetent and immunodeficient mice
  • Minimal tumor regression in NSCLC under similar dosing

Molecular Targets & Biomarkers (from in vitro studies)

• Histone Marks: H3K9ac, H3K18ac, H4K8ac, H4K16ac
• Cell Cycle & Apoptosis: p21, p27, cleaved PARP, cleaved caspase-3, caspase-8
• Transcription Factors: c-Myc, IRF4, Sp1
• Epigenetic Regulators: DNMT1, EZH2
• Others: RAD51, BRCA1, CHK1, Synaptophysin, NeuroD1

Experimental References

• PMIDs:
  • 31071955 (Western blot analysis)
  • 23544167 (Immunofluorescence)
  • 27738323 (Growth inhibition assay)

Applications

Epigenetic Therapy Research – HDAC inhibition, chromatin remodeling

Cancer Pharmacology – Leukemia, SCLC, NSCLC, mesothelioma, neuroblastoma

Latency-Reversing Agents – HIV reservoir disruption studies

Cell Cycle & Apoptosis Research – p21, c-Myc, caspase pathways

DNA Repair Pathway Modulation – BRCA1, RAD51, CHK1 expression analysis