N-Methylated Cyclic RGD Peptides as Highly Active and Selective αVβ3Integrin Antagonists

Dechantsreiter, Michael A.; Planker, Eckart; Mathä, Barbara; Lohof, Elisabeth; Hölzemann, Günter; Jonczyk, Alfred; Goodman, Simon L.; Kessler, Horst

doi:10.1021/jm970832g

Cited by 787 publications

(711 citation statements)

References 55 publications

Supporting

Mentioning

663

Contrasting

Unclassified

Order By: Relevance

“…The aVb3/aVb5 inhibitor EMD121974 sensitizes fibronectin-adherent HUVEC TNF/IFNg-induced death The aVb3/aVb5 inhibitory RGD-based cyclopeptide (Dechantsreiter et al, 1999) showed antiangiogenic effects in preclinical models (Alghisi and Ruegg, 2006). We used EMD121974 to test whether inhibition of aVb3/ aVb5 integrins in fibronectin-adherent HUVEC would sensitize HUVEC to TNF-induced death.…”

Section: Resultsmentioning

confidence: 99%

Distinctive role of integrin-mediated adhesion in TNF-induced PKB/Akt and NF-κB activation and endothelial cell survival

Bieler¹,

Hasmim²,

Monnier³

et al. 2007

Oncogene

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 99%

Distinctive role of integrin-mediated adhesion in TNF-induced PKB/Akt and NF-κB activation and endothelial cell survival

Bieler¹,

Hasmim²,

Monnier³

et al. 2007

Oncogene

View full text Add to dashboard Cite

“…As explained in a very recent and exhaustive review about the design and chemical synthesis of integrin ligands [118], small changes within the natural sequence of these molecules could deeply improve their activity profiles. For instance, in the c-RGDfV peptide, where f stands for a D-amino acid, each amino acid was replaced by its N-methylated form [136]. Depending on the structure-activity refinement of the N-methylation position for instance, the specific binding (IC50) varied from 10 -5 M for the c(RGD(NMe)fV) to 10 -8 M for the c(RGDf(NMe)V), which represents a gain of more than 1000 folds [118].…”

Section: Improving Ctpsmentioning

confidence: 99%

Cell-penetrating and cell-targeting peptides in drug delivery

Vivès

Schmidt

Pèlegrin

2008

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

317

272

View full text Add to dashboard Cite

During the last decade, the potential of peptides for drug delivery into cells has been highlighted by the discovery of several cell-penetrating peptides (CPPs). CPPs are very efficient in delivering various molecules into cells. However, except in some specific cases, their lack of cell specificity remains the major drawback for their clinical development. At the same time, various peptides with specific binding activity for a given cell line (cell-targeting peptides) have also been reported in the literature. One of the goals of the next years will be to optimize the tissue and cell delivery of therapeutic molecules by means of peptides which combine both targeting and internalization advantages. In this review, we describe the main strategies that are currently in use or likely to be employed in the near future to associate both targeting and delivery properties.

show abstract

“…Cilengitide blocks binding of vitronectin to isolated αvβ3 and αvβ5 with an IC 50 of 4 and 79 nM, respectively [87,88]. Cilengitide inhibits vitronectin/integrin binding with an IC 50 of 0.4 µm in cell adhesion assays using M21 and UCLA-P3 human melanoma cell lines, respectively [87].…”

Section: Pharmacodynamics and Preclinical Studiesmentioning

confidence: 99%

Cilengitide: An RGD Pentapeptide ανβ3 and ανβ5 Integrin Inhibitor in Development for Glioblastoma and Other Malignancies

et al. 2011

View full text Add to dashboard Cite

Cilengitide, a cyclicized arginine-glycine-aspartic acid-containing pentapeptide, potently blocks 3 and 5 integrin activation. Integrins are upregulated in many malignancies and mediate a wide variety of tumor-stroma interactions. Cilengitide and other integrin-targeting therapeutics have preclinical activity against many cancer subtypes including glioblastoma (GBM), the most common and deadliest CNS tumor. Cilengitide is active against orthotopic GBM xenografts and can augment radiotherapy and chemotherapy in these models. In Phase I and II GBM trials, cilengitide and the combination of cilengitide with standard temozolomide and radiation demonstrate consistent antitumor activity and a favorable safety profile. Cilengitide is currently under evaluation in a pivotal, randomized Phase III study cancer subtypes including glioblastoma (GBM), the most common and deadliest central nervous system (CNS) tumor. Cilengitide is active against orthotopic GBM xenografts and can augment radiotherapy and chemotherapy in these models. In phase I and II GBM trials, cilengitide and the combination of cilengitide with standard temozolomide (TMZ) and radiation demonstrate consistent anti-tumor activity and a favorable safety profile. Cilengitide is currently under evaluation in a pivotal, randomized phase III study (CENTRIC) for newly diagnosed GBM. In addition, randomized, controlled phase II studies with cilengitide are ongoing for non-small cell lung cancer and squamous cell carcinoma of the head and neck.Cilengitide is the first integrin-inhibitor in clinical phase III development for oncology.

show abstract

N-Methylated Cyclic RGD Peptides as Highly Active and Selective α_Vβ₃Integrin Antagonists

Cited by 787 publications

References 55 publications

Distinctive role of integrin-mediated adhesion in TNF-induced PKB/Akt and NF-κB activation and endothelial cell survival

Distinctive role of integrin-mediated adhesion in TNF-induced PKB/Akt and NF-κB activation and endothelial cell survival

Cell-penetrating and cell-targeting peptides in drug delivery

Cilengitide: An RGD Pentapeptide ανβ3 and ανβ5 Integrin Inhibitor in Development for Glioblastoma and Other Malignancies

Contact Info

Product

Resources

About