Cilengitide: The First Anti-Angiogenic Small Molecule Drug Candidate. Design, Synthesis and Clinical Evaluation
نویسندگان
چکیده
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 αvβ1. 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.
منابع مشابه
The recent development in synthesis and pharmacological evaluation of small molecule to treat Alzheimer's diseases: A review
Alzheimer's disease is a neurological disorder in which the death of brain cells causes memory loss and cognitive decline. A neurodegenerative type of dementia, the disease starts mild and gets progressively worse. Like all types of dementia, Alzheimer's is caused by brain cell death. The most common presentation marking Alzheimer's dementia is where symptoms of memory loss are the most promine...
متن کاملThe recent development in synthesis and pharmacological evaluation of small molecule to treat Alzheimer's diseases: A review
Alzheimer's disease is a neurological disorder in which the death of brain cells causes memory loss and cognitive decline. A neurodegenerative type of dementia, the disease starts mild and gets progressively worse. Like all types of dementia, Alzheimer's is caused by brain cell death. The most common presentation marking Alzheimer's dementia is where symptoms of memory loss are the most promine...
متن کاملCilengitide treatment for malignant glioma: current status and future direction.
Malignant glioma is the most common primary brain tumor and accounts for the majority of diagnoses. Treatment has involved a combination of surgery, radiation, and chemotherapy, yet these modalities rarely extend the life of the patient to more than one year from diagnosis. Integrins are expressed in tumor cells and tumor endothelial cells, and are important in angiogenesis and invasion in glio...
متن کاملDesign, Synthesis and Antitubercular Evaluation of Novel Series of Pyrazinecarboxamide Metal Complexes
The interest in the synthesis of metallic complexes of different drugs to make them moreefficient in biological environment of the human body is seen for the last few decades. Widerange of metal complexes are already used in clinical practice which encourages additionalresearch for innovating new metal based drugs, such as metal-mediated antibiotics, antiparasitic,antiviral, antibacterial, and ...
متن کاملDesign, Synthesis and Antitubercular Evaluation of Novel Series of Pyrazinecarboxamide Metal Complexes
The interest in the synthesis of metallic complexes of different drugs to make them moreefficient in biological environment of the human body is seen for the last few decades. Widerange of metal complexes are already used in clinical practice which encourages additionalresearch for innovating new metal based drugs, such as metal-mediated antibiotics, antiparasitic,antiviral, antibacterial, and ...
متن کامل