LB100, a small molecule inhibitor of PP2A with potent chemo- and radio-sensitizing potential

Cancer Biol Ther. 2015;16(6):821-33. doi: 10.1080/15384047.2015.1040961. Epub 2015 Apr 21.


Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase that plays a significant role in mitotic progression and cellular responses to DNA damage. While traditionally viewed as a tumor suppressor, inhibition of PP2A has recently come to attention as a novel therapeutic means of driving senescent cancer cells into mitosis and promoting cell death via mitotic catastrophe. These findings have been corroborated in numerous studies utilizing naturally produced compounds that selectively inhibit PP2A. To overcome the known human toxicities associated with these compounds, a water-soluble small molecule inhibitor, LB100, was recently developed to competitively inhibit the PP2A protein. This review summarizes the pre-clinical studies to date that have demonstrated the anti-cancer activity of LB100 via its chemo- and radio-sensitizing properties. These studies demonstrate the tremendous therapeutic potential of LB100 in a variety of cancer types. The results of an ongoing phase 1 trial are eagerly anticipated.

Keywords: ABC, ATP-binding cassette.; APC, adenomatous polyposis coli; ARPP19, cyclic AMP-regulated phosphoprotein 19; ATM, ataxia-telangiectasia mutated; CIP2A, cancerous inhibitor of PP2A; CNTF, ciliary neurotrophic factor; DISC, death-inducing signaling complex; DVL, dishevelled; ENSA, α-endosulphine; GBM, glioblastoma; GFAP, glial fibrillary acidic protein; HCC, hepatocellular carcinoma; HDACs, histone deacetylase complexes; HIF-1a, hypoxia-inducible factor-1a; HRR, homologous recombination repair; MDM2, mouse double minute 2 homolog; MRI, magnetic resonance imaging; NPC, nasopharyngeal carcinoma; PP2A, protein phosphatase 2A; Plk1, polo-like kinase 1; TCTP, translationally-controlled tumor protein; TMZ, temozolomide; TRAIL, TNF-related apoptosis-inducing ligand; VEGF, vascular endothelial growth factor; cell cycle; chemosensitization; mitotic catastrophe; protein phosphatase 2A; radiosensitizationreview; small molecule inhibitor.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
  • Cell Cycle / drug effects
  • Drug Evaluation, Preclinical
  • Drug Resistance, Neoplasm
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Mitosis / drug effects
  • Mitosis / genetics
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Oncogene Proteins / antagonists & inhibitors
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism
  • Piperazines / pharmacology*
  • Protein Phosphatase 2 / antagonists & inhibitors*
  • Protein Phosphatase 2 / genetics
  • Protein Phosphatase 2 / metabolism
  • Radiation-Sensitizing Agents / pharmacology*
  • Tumor Protein, Translationally-Controlled 1
  • Tumor Suppressor Proteins / antagonists & inhibitors
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism
  • Wnt Signaling Pathway / drug effects


  • Antineoplastic Agents
  • Bridged Bicyclo Compounds, Heterocyclic
  • Enzyme Inhibitors
  • LB100
  • Oncogene Proteins
  • Piperazines
  • Radiation-Sensitizing Agents
  • TPT1 protein, human
  • Tpt1 protein, mouse
  • Tumor Protein, Translationally-Controlled 1
  • Tumor Suppressor Proteins
  • Protein Phosphatase 2