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 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- 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
-
BRCA2 Dysfunction Promotes Malignant Transformation of Pancreatic Intraepithelial Neoplasia
Anti-Cancer Agents in Medicinal Chemistry Editorial [Bioorganic Chemistry Guest Editor: Harri Lonnberg]
Current Organic Chemistry INNO-206 (DOXO-EMCH), an Albumin-Binding Prodrug of Doxorubicin Under Development for Phase II Studies
Current Bioactive Compounds Carrier Based Oral Nano Drug Delivery Framework: A Review
Current Nanomaterials ACAT1 as a Therapeutic Target and its Genetic Relationship with Alzheimer's Disease
Current Alzheimer Research Experience with Androgen Deprivation Therapy for Prostate Cancer in Japan and Future Perspectives
Current Cancer Drug Targets Targeting SKCa Channels in Cancer: Potential New Therapeutic Approaches
Current Medicinal Chemistry Cytotoxic, Antiproliferative and Apoptotic Effects of Perillyl Alcohol and Its Biotransformation Metabolite on A549 and HepG2 Cancer Cell Lines
Anti-Cancer Agents in Medicinal Chemistry Lignans from Medicinal Plants and their Anticancer Effect
Mini-Reviews in Medicinal Chemistry Artificial Carriers: A Strategy for Constructing Antigenic/Immunogenic Conjugates
Current Topics in Medicinal Chemistry ω-3 Polyunsaturated Fatty Acids Effects on the Cardiometabolic Syndrome and their Role in Cardiovascular Disease Prevention: An Update from the Recent Literature
Recent Advances in Cardiovascular Drug Discovery (Discontinued) Enzalutamide: A Novel Anti-androgen with Prolonged Survival Rate in CRPC Patients
Mini-Reviews in Medicinal Chemistry Nanoparticles vs Cancer: A Multifuncional Tool
Current Topics in Medicinal Chemistry Synergy of microRNA and Stem Cell: A Novel Therapeutic Approach for Diabetes Mellitus and Cardiovascular Diseases
Current Diabetes Reviews Synthetic Approaches to Various Class of Topoisomerase II Inhibitors
Mini-Reviews in Organic Chemistry Current Management of Alcoholic Liver Disease
Current Drug Abuse Reviews Synthesis, 17α-hydroxylase-C17,20-lyase Inhibitory and 5AR Reductase Activity of Novel Pregnenolone Derivatives
Anti-Cancer Agents in Medicinal Chemistry Pharmaceutical Applications of Graphene-based Nanosheets
Current Pharmaceutical Biotechnology Structural and Functional Characterization of the Proteins Responsible for N<sup>6</sup>-Methyladenosine Modification and Recognition
Current Protein & Peptide Science Natural Products and Derivatives as Leads to Cell Cycle Pathway Targets in Cancer Chemotherapy
Current Cancer Drug Targets