Cilengitid

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Cilengitide
Cilengitide
Structural formula
Mass / length primary structure 5 amino acids, 589  daltons
Identifier
External IDs
Drug information
Drug class Angiogenesis inhibitor

Cilengitid (EMD 121974, brand name: Impetreve , single-letter code : cyclo- [RGDfN (Me) V]) is the international non-proprietary name for a cyclic penta peptide . It is currently being tested in oncology for its applicability as an angiogenesis inhibitor against glioblastomas , a particularly malignant form of brain tumors. It was developed by Merck KGaA in collaboration with Horst Kessler from the Technical University of Munich .

Mechanism of action

Structure of an integrin. The upper part is extracellular. In the case of an α v β 3 and α v β 5 integrin, cilengitide binds there.

Cilengitide includes a RGD - amino acid sequence . This sequence, consisting of the three amino acids arginine (R), glycine (G) and aspartic acid (D), mediates the binding to specific receptors, so-called integrins . Cilengitid inhibits the integrins α v β 3 and α v β 5 and is intended to prevent the formation and growth of tumor-specific blood vessels (angiogenesis) and thus the growth and spread of tumor cells. As a result, the blood supply is cut off, the tumor literally "starves" and can no longer form metastases . Some cancer cells even react very immediately to this substance and die ( apoptosis ).

Clinical testing

Cilengitide is not currently approved for use in humans. The substance is still in clinical trials.

  • The results of a multicenter dose-finding study to determine the maximum tolerated dose of cilengitide in glioma patients were published at the ninth annual meeting of the American Society for Neuro-Oncology (SNO) in Toronto: Complete remission was achieved in two of the 51 patients recruited, and one in three patients Partial remission and in four patients a stabilization of the disease state for more than six months.
  • Currently (as of June 2007) seven National Cancer Institute- funded studies are ongoing with cilengitide as monotherapy for a variety of tumor types including newly diagnosed glioblastoma , recurrent glioblastoma in adults, and recurrent brain tumors in children. Another NCI study is currently investigating the combination of cilengitide with radiation therapy and temozolomide in patients with newly diagnosed glioblastoma in a phase II setting.
  • At the last annual meeting of the American Society of Clinical Oncology (ASCO), the results of two further Phase I / II studies with cilengitide in the treatment of patients with glioblastoma were presented.
  • In addition, cilengitide is currently being tested against a variety of other tumors, such as metastatic prostate cancer (phase II), advanced non-small cell lung cancer (phase II), and advanced squamous cell carcinoma of the head and neck (phase I / II).

Individual evidence

  1. ↑ G. Schrimpf: Merck is considering objecting to the CHMP opinion on the use of Erbitux for the treatment of lung cancer. (PDF; 42 kB) Press release from Merck KGaA of July 23, 2009
  2. ↑ C. Mas-Moruno, F. Rechenmacher, H. Kessler: Cilengitide: The First Anti-Angiogenic Small Molecule Drug Candidate. Design, Synthesis and Clinical Evaluation In: Anti-Cancer Agents in Medicinal Chemistry ; 10, 2010, pp. 753-768. PMID 21269250
  3. ^ Report from the Technical University of Munich
  4. ↑ Cilengitide shows encouraging results in a phase I / IIa study for progression-free survival in patients with aggressive brain tumors (glioblastomas)
  5. ↑ Clinical Study (Phase II): Cilengitide in Treating Patients With Metastatic Prostate Cancer. at Clinicaltrials.gov the NIH
  6. ↑ Clinical Study (Phase II): Cilengitide in Treating Patients With Prostate Cancer. at Clinicaltrials.gov the NIH
  7. ↑ Clinical study (phase II): Cilengitide and Cetuximab in Combination With Platinum-based Chemotherapy as First-line Treatment for Subjects With Advanced Non Small Cell Lung Cancer. at Clinicaltrials.gov the NIH
  8. ↑ Clinical study (phase I / II): Cilengitide in Recurrent and / or Metastatic Squamous Cell Carcinoma of the Head and Neck. at Clinicaltrials.gov the NIH

literature