Abstract
Cilengitide, a cyclic RGD pentapeptide, is currently in clinical phase III for treatment of glioblastomas and in phase II for several other tumors. This drug is the first anti-angiogenic small molecule targeting the integrins αvβ3, αvβ5 and α5β1. It was developed by us in the early 90s by a novel procedure, the spatial screening. This strategy resulted in c(RGDfV), the first superactive αvβ3 inhibitor (100 to 1000 times increased activity over the linear reference peptides), which in addition exhibited high selectivity against the platelet receptor αIIbβ3. This cyclic peptide was later modified by N-methylation of one peptide bond to yield an even greater antagonistic activity in c(RGDf(NMe)V). This peptide was then dubbed Cilengitide and is currently developed as drug by the company Merck-Serono (Germany). This article describes the chemical development of Cilengitide, the biochemical background of its activity and a short review about the present clinical trials. The positive anti-angiogenic effects in cancer treatment can be further increased by combination with “classical” anti-cancer therapies. Several clinical trials in this direction are under investigation.
Keywords: RGD peptides, integrin antagonists, glioblastoma, N-methylation, conformational restriction, cyclization, Anti-Angiogenic, RGD, ECM, CAM, Angiogenesis, Tumor Vasculature, IMD, NMR, VEGFs, Cilengitide, NSCLC, radio-chemotherapy, ITH, GBM
Anti-Cancer Agents in Medicinal Chemistry
Title: Cilengitide: The First Anti-Angiogenic Small Molecule Drug Candidate. Design, Synthesis and Clinical Evaluation
Volume: 10 Issue: 10
Author(s): Carlos Mas-Moruno, Florian Rechenmacher and Horst Kessler
Affiliation:
Keywords: RGD peptides, integrin antagonists, glioblastoma, N-methylation, conformational restriction, cyclization, Anti-Angiogenic, RGD, ECM, CAM, Angiogenesis, Tumor Vasculature, IMD, NMR, VEGFs, Cilengitide, NSCLC, radio-chemotherapy, ITH, GBM
Abstract: Cilengitide, a cyclic RGD pentapeptide, is currently in clinical phase III for treatment of glioblastomas and in phase II for several other tumors. This drug is the first anti-angiogenic small molecule targeting the integrins αvβ3, αvβ5 and α5β1. It was developed by us in the early 90s by a novel procedure, the spatial screening. This strategy resulted in c(RGDfV), the first superactive αvβ3 inhibitor (100 to 1000 times increased activity over the linear reference peptides), which in addition exhibited high selectivity against the platelet receptor αIIbβ3. This cyclic peptide was later modified by N-methylation of one peptide bond to yield an even greater antagonistic activity in c(RGDf(NMe)V). This peptide was then dubbed Cilengitide and is currently developed as drug by the company Merck-Serono (Germany). This article describes the chemical development of Cilengitide, the biochemical background of its activity and a short review about the present clinical trials. The positive anti-angiogenic effects in cancer treatment can be further increased by combination with “classical” anti-cancer therapies. Several clinical trials in this direction are under investigation.
Export Options
About this article
Cite this article as:
Mas-Moruno Carlos, Rechenmacher Florian and Kessler Horst, Cilengitide: The First Anti-Angiogenic Small Molecule Drug Candidate. Design, Synthesis and Clinical Evaluation, Anti-Cancer Agents in Medicinal Chemistry 2010; 10 (10) . https://dx.doi.org/10.2174/187152010794728639
DOI https://dx.doi.org/10.2174/187152010794728639 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
99mTc-labeling of Peptidomimetic Antagonist to Selectively Target αvβ3 Receptor-Positive Tumor: Comparison of PDA and EDDA as Co-Ligands
Current Radiopharmaceuticals Recent Advance in the Pharmacology of Dihydropyrimidinone
Mini-Reviews in Medicinal Chemistry Docking and Molecular Dynamics Study on the Inhibitory Activity of Novel Inhibitors on Epidermal Growth Factor Receptor (EGFR)
Medicinal Chemistry Cervical Cancer Prevention: More than Just a Pap in a Diverse Urban Community
Current Women`s Health Reviews Turning to Computer-aided Drug Design in the Treatment of Diffuse Large B-cell Lymphoma: Has it been Helpful?
Anti-Cancer Agents in Medicinal Chemistry Ruxolitinib Regulates the Autophagy Machinery in Multiple Myeloma Cells
Anti-Cancer Agents in Medicinal Chemistry Role of Ectonucleotidases in Synapse Formation During Brain Development: Physiological and Pathological Implications
Current Neuropharmacology Prokaryotic Arsenate Reductase Enhances Arsenate Resistance in Mammalian Cells
Recent Patents on Food, Nutrition & Agriculture METCAM/MUC18 Expression and Cancer Metastasis
Current Genomics The Chick Embryo Chorioallantoic Membrane as a Model for in vivo Research on Anti-Angiogenesis
Current Pharmaceutical Biotechnology Design and Synthesis of 4-substituted Quinazolines as Potent EGFR Inhibitors with Anti-breast Cancer Activity
Anti-Cancer Agents in Medicinal Chemistry Mass Spectrometry Based Proteomics for Interrogating the Histone Code
Current Proteomics Analysis of Key GO Terms and KEGG Pathways Associated with Carcinogenic Chemicals
Combinatorial Chemistry & High Throughput Screening A Review of the Treatment Strategies for Small Cell Lung Carcinoma Patients with a Poor Performance Status
Current Respiratory Medicine Reviews Prophylactic Vaccine Approach for Colon and Pancreatic Cancers: Present and Future
Current Medicinal Chemistry HDACs and HDAC Inhibitors in Urothelial Carcinoma – Perspectives for an Antineoplastic Treatment
Current Medicinal Chemistry Formulation and In Vitro Evaluation of Gelatin Nanospheres for the Oral Delivery of Selegiline
Current Nanoscience T Lymphocytes as Targets of Gene Transfer with Moloney-Type Retroviral Vectors
Current Gene Therapy Fluorescent Porphyrin with an Increased Uptake in Peripheral Blood Cell Subpopulations from Colon Cancer Patients
Medicinal Chemistry Erratum to Design, Synthesis and Biological Evaluation of a Phenyl Butyric Acid Derivative, N-(4-chlorophenyl)-4- phenylbutanamide: A HDAC6 Inhibitor with Anti-proliferative Activity on Cervix Cancer and Leukemia Cells
Anti-Cancer Agents in Medicinal Chemistry