title: TT232, a novel signal transduction inhibitory compound in the therapy of cancer and inflammatory diseases.
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.
authors.affiliation: Rational Drug Design Laboratories, Cooperative Research Center, Semmelweis University, Budapest, Hungary.
authors.forename: Orsolya
authors.initials: O
authors.lastname: Szokolóczi
authors.forename: Richárd
authors.initials: R
authors.lastname: Schwab
authors.forename: István
authors.initials: I
authors.lastname: Peták
authors.forename: László
authors.initials: L
authors.lastname: Orfi
authors.forename: Akos
authors.initials: A
authors.lastname: Pap
authors.forename: Alex N
authors.initials: AN
authors.lastname: Eberle
authors.forename: Tamás
authors.initials: T
authors.lastname: Szüts
authors.forename: György
authors.initials: G
authors.lastname: Kéril
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010456:Peptides, Cyclic / Q000235:genetics / Q000627:therapeutic use*; D017481:Receptors, Somatostatin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013004:Somatostatin / Q000031:analogs & derivatives
chemical_list: D000596:Amino Acids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D010456:Peptides, Cyclic; D017481:Receptors, Somatostatin; C094462:TT2-32; D013004:Somatostatin