What Is Cilengitide? Definition and What Research Reports

Definition

Cilengitide is a synthetic cyclic pentapeptide built around the arginine–glycine–aspartic acid (RGD) sequence — written in the literature as cyclo(Arg-Gly-Asp-D-Phe-N-Me-Val) or cyclo(RGDf[NMe]V). It was engineered to occupy the RGD-binding pocket of the αvβ3 and αvβ5 integrin receptors, which normally anchor cells to matrix proteins such as vitronectin and fibronectin. Reviews of integrin-targeted therapeutics have described cilengitide as one of the first RGD-mimetic integrin antagonists to be carried from structure-based peptide design into clinical oncology testing (PMID 21547158), and reviews of integrins in cancer place it within the broader effort to drug adhesion receptors rather than the tumour cells themselves (PMID 20029421). This page is for educational purposes only and is not medical advice; consult a licensed physician about any compound or medical condition.

What Class of Molecule Is It, and Where Does It Come From?

Cilengitide is not a hormone, a growth factor or a naturally occurring signalling peptide. It is a fully synthetic, chemically constrained peptide: the ring closure, the D-phenylalanine residue and the N-methylated valine were introduced to lock the RGD motif into a conformation that favours αv-class integrins and to slow enzymatic breakdown compared with a linear peptide. The design logic came from the observation that many extracellular matrix ligands present an RGD tripeptide to integrin receptors; short cyclic peptides that mimic that presentation can compete for the same site. Integrin-targeting reviews group cilengitide with antibodies, peptidomimetics and imaging conjugates aimed at the same receptor family (PMID 21547158).

Because αvβ3 and αvβ5 are expressed on activated endothelium, on some tumour cells and on several immune and stromal populations, the same molecule has been used in very different experimental contexts — vascular biology, fibrosis, neuroinflammation and tumour microenvironment work — wherever researchers wanted to interrupt RGD-dependent integrin engagement.

How the Term Is Used in Peptide Research

In modern papers, "cilengitide" is most often encountered as a pharmacological tool: a named integrin blocker applied to cells or animals to test whether an observed effect depends on αv integrin signalling. When a paper reports that a phenotype was reversed or prevented by cilengitide, the intended reading is that the pathway runs through RGD-binding integrins. The term therefore functions in two ways at once — as the name of a specific investigational compound, and as shorthand for "αvβ3/αvβ5 blockade" in a mechanism experiment.

Contexts in Which the Cited Literature Discusses αv Integrins and Their Blockade

What the Published Literature Reports

The literature on cilengitide itself is largely a literature about integrin biology. Reviews of integrins in cancer reported that αv-class receptors sit at the intersection of tumour cell adhesion, angiogenesis and stromal remodelling, which is why they attracted therapeutic interest in the first place (PMID 20029421), and a companion review of integrin-targeted therapeutics catalogued the peptide, antibody and small-molecule strategies developed against those receptors (PMID 21547158).

Downstream work has continued to test whether αv integrin engagement drives specific disease processes. Researchers reported that irisin attenuated acute glaucoma-induced neuroinflammation by acting through microglial integrin αVβ5 and AMPK signalling and by promoting autophagy (PMID 38955026). A 2025 study reported that induction of endothelial αvβ3 integrin during hypoxia protected blood–brain barrier integrity, a finding that frames αv integrin activity as context-dependent rather than uniformly harmful (PMID 40961140). In fibrosis, the study of TGFβ1 activation reported that blocking that activation step prevented radiation-induced lung fibrosis (PMID 38239077), and separate work reported that salvianolic acid B attenuated liver fibrosis by targeting ECM1 and inhibiting hepatocyte ferroptosis (PMID 38184998) — both pathways in which matrix–integrin coupling is under active study.

Cancer-microenvironment papers use the same receptor family as a handle. A spatial-transcriptomics study reported that GPNMB-positive macrophages interacted with COL6A3-positive fibroblasts to enhance vascular fibrosis in glioblastoma (PMID 41174767). Other groups reported that integrin-mediated TIMP1 signalling reprogrammed liver macrophages and accelerated colorectal cancer metastasis (PMID 41511313), that combined inhibition of surface CD51 (the αv integrin subunit) and its γ-secretase-mediated cleavage improved therapeutic efficacy in experimental metastatic hepatocellular carcinoma (PMID 37604269), and that KIF1Bβ suppressed hepatocellular carcinoma by transporting and secreting FBLN5 to attenuate the integrin pathway (PMID 41087058). Integrin-adjacent immunology also appears: one study reported that Bacteroides fragilis toxin suppressed METTL3-mediated m6A modification in macrophages to promote inflammatory bowel disease (PMID 40065724).

Clinical Development History: What Studies Report

Cilengitide is not an approved medicine in the United States or the European Union. A 2015 review of oncology drugs whose development was discontinued in 2013 covered the agents whose programmes were halted that year, cilengitide among them (PMID 25315907). Material sold or distributed under this name outside of authorised clinical research is generally labelled research-use-only and is not a prescription product. The verified sources summarised here do not provide human dosing schedules or an adverse-event profile for cilengitide, so none is described on this page.

Terms Frequently Confused With Cilengitide

• RGD peptides — the general class of short arginine–glycine–aspartic acid sequences; cilengitide is one constrained, N-methylated member of that class (PMID 21547158).
• αvβ3 / αvβ5 integrins — the receptors, not the blocker; reviews reported that these receptors have distinct roles across endothelium, immune cells and tumour stroma (PMID 20029421).
• CD51 — another name for the integrin αv subunit, targeted directly in the hepatocellular carcinoma study described above (PMID 37604269).

Limitations of the Evidence

Most of the work cited here is preclinical — cell culture, animal models and spatial or molecular profiling — or is review-level synthesis rather than trial data. Findings in rodents or in dissected tumour microenvironments do not translate automatically to humans, and results describing αv integrin biology are not interchangeable with results for any one compound that blocks those receptors. The 2025 blood–brain barrier study is a useful reminder that the same receptor can be protective in one setting while contributing to pathology in another (PMID 40961140).

References

• Integrins in cancer: biological implications and therapeutic opportunities (Nature Reviews Cancer, 2010)
• Integrin targeted therapeutics (Theranostics, 2011)
• Discontinued in 2013: oncology drugs (Expert Opinion on Investigational Drugs, 2015)
• Irisin attenuates acute glaucoma-induced neuroinflammation by activating microglia-integrin αVβ5/AMPK and promoting autophagy (International Immunopharmacology, 2024)
• Endothelial αvβ3 integrin induction during hypoxia protects blood-brain barrier integrity (PNAS, 2025)
• Inhibition of TGFβ1 activation prevents radiation-induced lung fibrosis (Clinical and Translational Medicine, 2024)
• Salvianolic acid B attenuates liver fibrosis by targeting Ecm1 and inhibiting hepatocyte ferroptosis (Redox Biology, 2024)
• Spatial-reprogramming derived GPNMB(+) macrophages interact with COL6A3(+) fibroblasts to enhance vascular fibrosis in glioblastoma (Genome Medicine, 2025)
• Integrin-Mediated TIMP1 Signaling Reprograms Liver Macrophages and Accelerates Colorectal Cancer Metastasis (Cells, 2025)
• Combined inhibition of surface CD51 and γ-secretase-mediated CD51 cleavage improves therapeutic efficacy in experimental metastatic hepatocellular carcinoma (Journal of Hepatology, 2023)
• KIF1Bβ suppresses hepatocellular carcinoma by transporting and secreting FBLN5 to attenuate the integrin pathway (Gut, 2026)
• Bacteroides fragilis Toxin Suppresses METTL3-Mediated m6A Modification in Macrophage to Promote Inflammatory Bowel Disease (Journal of Crohn's & Colitis, 2025)