TT232, a novel signal transduction inhibitory compound in the therapy of cancer and inflammatory diseases

J Recept Signal Transduct Res. 2005;25(4-6):217-35. doi: 10.1080/10799890500464621.

Abstract

TT-232 is a structural analogue of somatostatin exhibiting strong and selective growth-inhibitory effects, inhibition of neurogenic inflammation, as well as general anti-inflammatory and analgesic potential without the wide-ranging endocrine side effects of the parent hormone and its "traditional" analogues. The anti-inflammatory action of TT-232 is mediated through the SSTR4 receptor, and its antitumor activity is mediated through the SSTR1 receptor and by the tumor-specific isoform of pyruvate kinase. Its mechanism of action is in line with a new era of molecular medicine called signal transduction therapy, where "false" intracellular or intercellular communication is inhibited or corrected without interfering with basic cell functions and machinery. TT232 has passed phase I clinical trials without toxicity and significant side effects, and phase II studies are running for oncological and anti-inflammatory indications, respectively. This compound has the perspective to become the first drug in molecularly targeted therapy of inflammation where a combined effect of anti-inflammatory, analgesic, and neurogenic inflammation-inhibiting activity can be achieved.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Amino Acids / chemistry
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / physiology
  • Cell Cycle / physiology
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Enzyme Activation
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Molecular Sequence Data
  • Molecular Structure
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Peptides, Cyclic / genetics
  • Peptides, Cyclic / therapeutic use*
  • Receptors, Somatostatin / metabolism
  • Signal Transduction / physiology*
  • Somatostatin / analogs & derivatives

Substances

  • Amino Acids
  • Anti-Inflammatory Agents, Non-Steroidal
  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Peptides, Cyclic
  • Receptors, Somatostatin
  • TT2-32
  • Somatostatin