Cilengitide
What the Research Actually Shows
Human: 3 studies, 3 groups · Animal: 0 · In Vitro: 0
The RGD peptide that was supposed to starve tumors by cutting off their blood supply — and what 545 patients taught us about the limits of preclinical promise
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BLUF: Bottom Line Up Front
Cilengitide was a peptide designed to starve brain tumors by blocking the proteins they use to build new blood vessels. In lab studies, it looked like a breakthrough — it stopped blood vessel growth, killed tumor cells, and worked even better when combined with radiation and chemotherapy. Then it was tested in 545 patients with the most common lethal brain tumor (glioblastoma), and the results were devastating: patients lived an identical 26.3 months whether they received cilengitide or not. The hazard ratio was 1.02 — as close to zero effect as a cancer trial can produce. The drug was safe. It simply did nothing in humans. Development was stopped, and cilengitide became the textbook example of why animal studies don't always predict what happens in people.
Cilengitide was the great hope of integrin-targeted antiangiogenic therapy — a cyclic pentapeptide built around the RGD (Arg-Gly-Asp) motif, one of the most studied peptide sequences in all of biology. The RGD motif is the universal recognition signal for integrin receptors, and integrins αvβ3 and αvβ5 are overexpressed on the blood vessels that tumors recruit to feed their growth. Block those integrins with a peptide, the hypothesis went, and you could starve tumors by cutting off their blood supply.
The preclinical evidence was genuinely compelling. Cilengitide inhibited angiogenesis in multiple animal models, showed antitumor activity against glioblastoma xenografts, and synergized with both radiation and temozolomide in preclinical combination studies. Phase I/II data showed occasional durable responses that sustained enthusiasm through a decade of clinical development.
The CENTRIC trial (N=545) was designed to give cilengitide its best chance: newly diagnosed glioblastoma patients with MGMT promoter methylation — the population most responsive to temozolomide-based therapy and most likely to benefit from an additional agent. The result was a hazard ratio of 1.02 for overall survival (PMID 25349218). Not a modest benefit. Not a trend. A flat null — 26.3 months with cilengitide, 26.3 months without. Merck Serono discontinued development, and cilengitide joined the long list of compounds that proved the gap between preclinical promise and clinical reality is not a crack but a canyon.
In This Article
Quick Facts: Cilengitide at a Glance
Type
Synthetic cyclic RGD pentapeptide integrin antagonist (5 amino acids)
Also Known As
EMD 121974, cilengitide
Generic Name
Cilengitide
Brand Name
None (never approved — development discontinued)
Related Compounds
Other RGD-based integrin inhibitors (none approved for cancer), bevacizumab (anti-VEGF antibody — different antiangiogenic mechanism)
WADA Status
Not on WADA Prohibited Lists
Community Interest
No community use. Discontinued investigational compound. Not available from any source
Molecular Weight
~589 Da
Peptide Sequence
cyclo(Arg-Gly-Asp-D-Phe-N-Me-Val) — cyclic pentapeptide incorporating the RGD integrin recognition motif
Endogenous Origin
Based on the RGD (Arg-Gly-Asp) motif found in extracellular matrix proteins (fibronectin, vitronectin) that bind integrin receptors
Primary Molecular Function
Selective antagonist of αvβ3 and αvβ5 integrins — blocks integrin-mediated endothelial cell adhesion, migration, and survival → antiangiogenic effect
Active Fragment
The RGD tripeptide is the pharmacophore. Cyclization + D-Phe + N-Me-Val provide selectivity for αvβ3/αvβ5 over other RGD-binding integrins
Route
Intravenous infusion (30 minutes, twice weekly)
Clinical Programs
CENTRIC Phase III (N=545, GBM — FAILED), CORE Phase II (N=265, GBM — FAILED). All development discontinued
FDA Status
Never approved. Phase III failed definitively (CENTRIC, 2014). Development discontinued by Merck Serono
Half-Life
~4 hours (IV). Short half-life may have contributed to insufficient target engagement — twice-weekly dosing may not maintain adequate integrin occupancy
Evidence Tier
2 Clinical Trials
Verdict
Thin Ice
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Subscribe to Peptidings WeeklyWhat Is Cilengitide?
Pronunciation: sih-LEN-jih-tide
Every tumor, once it grows beyond a millimeter or two, faces a supply problem. Cancer cells divide fast and demand oxygen and nutrients. Without new blood vessels to deliver that supply, the tumor cannot grow beyond the size of a pinhead. This process of recruiting new blood vessels — angiogenesis — is one of the hallmarks of cancer, and blocking it has been a major therapeutic strategy for decades.
Cilengitide was designed to block angiogenesis at one of its most fundamental control points: integrin receptors. Integrins αvβ3 and αvβ5 are adhesion proteins expressed on the surface of endothelial cells — the cells that line blood vessels. When these integrins bind to extracellular matrix proteins via the RGD (Arg-Gly-Asp) motif, they send survival and migration signals that allow new blood vessels to form and grow toward the tumor.
Cilengitide is a cyclic pentapeptide — five amino acids arranged in a ring — that mimics the RGD motif and competitively blocks αvβ3 and αvβ5 binding. In theory, this should prevent the survival signals that new blood vessel cells need, causing them to die before they reach the tumor and cutting off the tumor's blood supply.
The theory worked beautifully in mice. It failed completely in humans.
PLAIN ENGLISH
Cilengitide was a peptide designed to block a key receptor that helps tumors grow new blood vessels. Without blood vessels, tumors can't grow. The idea was sound, and it worked in lab studies — but when tested in a major trial of 545 brain cancer patients, the drug did absolutely nothing. Patients lived the same length of time with or without it.
Origins and Discovery
The RGD motif — arginine-glycine-aspartic acid — was identified in the 1980s as the minimal adhesion signal in fibronectin, the extracellular matrix protein that mediates cell attachment. The discovery that this three-amino-acid sequence was recognized by multiple integrin receptors launched an entire field of peptide-based drug design targeting cell adhesion.
Cilengitide was developed at Merck KGaA (EMD Serono) as a synthetic cyclic peptide optimized for selective αvβ3/αvβ5 antagonism. The cyclization (forming a five-membered ring) and incorporation of non-natural amino acids (D-Phe and N-methylvaline) provided receptor selectivity and metabolic stability beyond what the linear RGD tripeptide could achieve. The compound was designated EMD 121974.
Preclinical testing was extensive and consistently positive. In glioblastoma xenograft models, cilengitide inhibited tumor growth and reduced tumor vasculature. Combination with temozolomide and radiation showed synergistic effects. Phase I testing established the 2,000 mg IV dose with a favorable safety profile, and Phase I/II results in recurrent glioblastoma showed occasional durable responses (PMID 18695192) — enough to justify the large investment in a Phase III trial.
The CENTRIC trial was launched by Merck Serono as one of the most ambitious integrin-targeted oncology programs ever undertaken. It enrolled 545 patients across 145 centers in 23 countries between 2008 and 2013.
Mechanism of Action
Integrin Biology and the Antiangiogenic Hypothesis
Integrins are heterodimeric transmembrane receptors — each consists of an alpha and a beta subunit — that mediate cell adhesion to the extracellular matrix. αvβ3 and αvβ5 are expressed on activated endothelial cells during angiogenesis and on certain tumor cell types, including glioblastoma.
When endothelial cells bind extracellular matrix proteins (vitronectin, fibronectin, osteopontin) via αvβ3/αvβ5, intracellular signaling cascades activate: - FAK (focal adhesion kinase): Promotes cell survival and migration - PI3K/Akt pathway: Anti-apoptotic signaling - Ras/MAPK pathway: Proliferation signaling
Cilengitide competitively blocks the RGD binding site on αvβ3 and αvβ5, preventing matrix protein binding and disrupting these survival signals. Without adhesion-mediated survival signaling, endothelial cells undergo anoikis — detachment-induced apoptosis.
PLAIN ENGLISH
Blood vessel cells need to grab onto the surrounding tissue to survive. Integrins are the hands they grab with. Cilengitide was designed to block those hands, causing the cells to let go and die — which should prevent new blood vessels from reaching the tumor.
Why the Mechanism Didn't Translate
Several explanations have been proposed for cilengitide's clinical failure:
Short half-life (~4 hours): Cilengitide is cleared rapidly from the bloodstream. Twice-weekly IV dosing may not maintain sufficient integrin occupancy to sustain the antiangiogenic effect. Between doses, integrins may re-engage their ligands and resume pro-angiogenic signaling.
Low-dose stimulation paradox: Preclinical data published after CENTRIC suggested that subtherapeutic cilengitide concentrations could paradoxically stimulate angiogenesis by activating VEGFR2 signaling. If trough levels between doses fell into this pro-angiogenic range, the drug may have intermittently promoted the very process it was designed to inhibit.
Target redundancy: Glioblastoma employs multiple angiogenic pathways. Blocking αvβ3/αvβ5 alone may be insufficient if tumors can recruit blood vessels through alternative mechanisms (VEGF, FGF, PDGF pathways).
Target validation: αvβ3 and αvβ5 may not be the rate-limiting integrins for angiogenesis in human glioblastoma. Preclinical models may have overrepresented their importance relative to human disease biology.
PLAIN ENGLISH
Four possible reasons the drug failed: (1) it left the body too quickly, (2) at low levels between doses it may have actually promoted blood vessel growth, (3) tumors have backup methods for growing blood vessels, and (4) the target may not have been as important in human brain tumors as it appeared in mice.
Key Research Areas and Studies
CENTRIC — The Definitive Negative Trial (PMID 25349218)
CENTRIC was one of the largest and most carefully designed trials in glioblastoma history.
Design: Randomized, open-label Phase III. 545 patients with newly diagnosed glioblastoma and MGMT promoter methylation — the biomarker subset most responsive to temozolomide and most likely to benefit from an additional agent.
Treatment: Standard Stupp regimen (temozolomide + radiotherapy followed by adjuvant temozolomide) ± cilengitide 2,000 mg IV twice weekly throughout treatment.
Results: - Overall survival: 26.3 months (cilengitide) vs. 26.3 months (control) — HR 1.02 (95% CI 0.81–1.29, p=0.86) - PFS: 13.5 months vs. 10.7 months — HR 0.93 (95% CI 0.75–1.15, not significant) - The OS result is as close to a perfect null as a large oncology trial can produce
PLAIN ENGLISH
CENTRIC was designed to give cilengitide its absolute best shot — the patients most likely to respond, the best standard treatment as a backbone, and enough patients to detect even a modest benefit. The result: identical survival. 26.3 months with the drug, 26.3 months without it. The drug did nothing detectable.
CORE — Confirmation in Unmethylated GBM (PMID 26124478)
Design: Randomized Phase II. 265 patients with newly diagnosed GBM without MGMT methylation. Results: OS 16.3 months (cilengitide) vs. 14.5 months (control) — not statistically significant. Significance: Confirmed the CENTRIC null in a complementary GBM population. Cilengitide had no meaningful effect regardless of MGMT status.
Phase I/II — The Data That Generated Hope (PMID 18695192)
Design: Phase I/II single-arm. 81 patients with recurrent GBM. Cilengitide monotherapy. Results: 6-month PFS: 15% (compared to historical 9–15%). Why it was misleading: Single-arm data with historical comparisons are unreliable in GBM, where patient selection, supportive care, and disease heterogeneity create wide variability. The modest signal was real but insufficient to predict CENTRIC's null.
The Preclinical-to-Clinical Translation Gap
Cilengitide's story is the purest illustration on Peptidings of a phenomenon that affects all of drug development: the gap between what works in animal models and what works in patients.
The preclinical data was not fraudulent, not sloppy, not obviously flawed. Cilengitide genuinely inhibited angiogenesis in mouse models. It genuinely killed glioblastoma cells in xenograft studies. It genuinely synergized with temozolomide and radiation in preclinical combination experiments. The scientists who designed these studies and the regulators who approved the Phase III trial were not making an unreasonable bet.
But animal models of glioblastoma — typically human tumor cells implanted in immunocompromised mice — differ from human disease in fundamental ways. The tumor microenvironment is different. The immune system is absent. The blood-brain barrier dynamics are altered. The angiogenic redundancy that characterizes human GBM may not be fully replicated in a xenograft model.
The lesson is not that preclinical data is worthless — it is that preclinical data is a hypothesis, not a prediction. CENTRIC was the experiment that tested the hypothesis. The hypothesis was wrong.
For Peptidings readers accustomed to evaluating peptide compounds based on rodent studies, cilengitide is the essential reference point: even the strongest preclinical portfolio can produce a flat null when it encounters human biology.
PLAIN ENGLISH
Cilengitide worked in mice but not in people. This isn't because the lab studies were bad — they were solid. It's because human brain tumors are more complex than mouse models can capture. This is the cautionary tale that every claim based on "animal studies show..." needs to be weighed against.
Claims vs. Evidence
| Claim | What the Evidence Shows | Verdict |
|---|---|---|
| “"Cilengitide inhibits angiogenesis"” | Demonstrated in multiple preclinical models. Not validated in human GBM by CENTRIC — no clinical evidence of antiangiogenic effect in patients. | Mixed Evidence |
| “"Cilengitide improves survival in glioblastoma"” | CENTRIC Phase III (N=545): OS HR 1.02 (p=0.86). Identical survival. Definitively negative. PMID 25349218 | Unsupported |
| “"Cilengitide synergizes with temozolomide and radiation"” | Demonstrated in preclinical models. CENTRIC tested this combination in humans and found no added benefit. | Unsupported |
| “"RGD peptides are effective cancer drugs"” | Cilengitide was the most clinically advanced RGD-based cancer therapy. It failed definitively. No other RGD peptide has achieved Phase III success in oncology. | Unsupported |
| “"Integrin αvβ3 is a validated cancer target"” | αvβ3 is expressed on tumor vasculature, but blocking it with cilengitide did not improve outcomes. The target may not be rate-limiting in human GBM angiogenesis. | Mixed Evidence |
| “"Cilengitide is safe"” | CENTRIC confirmed no significant increase in adverse events over standard chemoradiation. The drug was well-tolerated. It simply didn't work. | Supported |
| “"The failure was due to pharmacokinetics, not the target"” | Short half-life (~4 hours) and potential low-dose stimulation paradox may have contributed. This is a post-hoc hypothesis — not definitively proven. | Theoretical |
| “"A better integrin inhibitor could succeed where cilengitide failed"” | Theoretically possible — but no alternative integrin-targeting peptide has advanced to Phase III in oncology since CENTRIC. | Theoretical |
| “"Cilengitide showed responses in Phase I/II"” | 6-month PFS of 15% in 81 patients (single-arm). Within historical range for recurrent GBM. Insufficient to predict benefit in a controlled trial. | Mixed Evidence |
| “"Preclinical antiangiogenic data predicts clinical efficacy"” | Cilengitide had consistently positive preclinical data across multiple models. CENTRIC showed zero clinical benefit. Preclinical antiangiogenesis data is hypothesis-generating, not predictive. | Unsupported |
| “"Cilengitide could work in other cancer types"” | Never tested in a Phase III setting outside GBM. No clinical data supports this claim. | Theoretical |
| “"The antiangiogenic approach to cancer is failed"” | Bevacizumab (anti-VEGF antibody) is FDA-approved for multiple cancers. The approach works — cilengitide's failure was specific to integrin-targeted peptides, not antiangiogenesis as a strategy. | Unsupported |
The Human Evidence Landscape
CENTRIC (Stupp et al., 2014, PMID 25349218)
Design: Randomized, open-label Phase III Population: 545 patients with newly diagnosed glioblastoma, MGMT promoter methylated Intervention: Standard chemoradiation (temozolomide + RT) ± cilengitide 2,000 mg IV twice weekly Key finding: OS 26.3 vs. 26.3 months, HR 1.02 (95% CI 0.81–1.29, p=0.86). PFS 13.5 vs. 10.7 months, HR 0.93 (not significant). Definitive negative trial. Limitations: Open-label (no blinding). MGMT-methylated GBM only — cannot rule out benefit in other GBM subpopulations (though CORE subsequently showed no benefit in unmethylated GBM either). Pharmacokinetic concerns (short half-life, twice-weekly dosing) raise questions about whether the drug was tested at optimal exposure.
CORE (Nabors et al., 2015, PMID 26124478)
Design: Randomized Phase II Population: 265 patients with newly diagnosed GBM without MGMT methylation Intervention: Standard chemoradiation ± cilengitide (standard or intensified schedule) Key finding: OS 16.3 vs. 14.5 months — not significant. Confirmed null in complementary population. Limitations: Phase II (not powered for OS). Explored intensified dosing schedule but still found no benefit.
Phase I/II (Reardon et al., 2008, PMID 18695192)
Design: Phase I/II single-arm Population: 81 patients with recurrent glioblastoma Key finding: 6-month PFS 15%. Some patients with durable responses. Limitations: Single-arm with historical comparison. No control group. Patient selection bias. Ultimately not predictive of CENTRIC outcome.
Safety, Risks, and Limitations
A Safe Drug That Didn't Work
Cilengitide's safety profile was its one unambiguous success. In CENTRIC, there was no significant increase in adverse events compared to standard chemoradiation alone:
No increased bleeding risk: Despite theoretical concerns that blocking integrins on platelets and endothelial cells might impair hemostasis, cilengitide did not increase hemorrhagic events — a meaningful finding given that GBM patients undergo craniotomy and are at baseline bleeding risk.
No wound healing impairment: Another theoretical concern with antiangiogenic agents. Not observed.
GI effects, fatigue, headache: At rates consistent with temozolomide and glioblastoma disease effects. No signal attributable to cilengitide.
PLAIN ENGLISH
The one clear finding from cilengitide's clinical development is that the drug was safe. Patients tolerated it well with no significant additional side effects. The problem was never safety — it was that the drug had no detectable effect on tumor growth or patient survival.
The Risk of False Hope
Cilengitide's primary harm, in retrospect, was not physical but informational. A decade of clinical development, hundreds of patients enrolled in trials, and significant research resources were invested in a target that ultimately contributed nothing to patient outcomes. Patients in CENTRIC received a drug that did nothing — they weren't harmed physically, but they were enrolled in a trial based on a hypothesis that proved false.
Legal and Regulatory Status
Never Approved
Cilengitide never received FDA approval for any indication. The CENTRIC Phase III trial failed to demonstrate any survival benefit, and Merck Serono discontinued all clinical development.
Current Status
Cilengitide is not commercially available. It is not in clinical trials. It is not available from research suppliers in any capacity relevant to clinical use. The compound exists solely as a historical reference in the literature.
Intellectual Property
Merck KGaA retains the intellectual property but has no active development program. The compound's patent estate is academically relevant but commercially dormant.
Research Protocols and Formulation Considerations
Formulation
Cilengitide was supplied as a solution for IV infusion, administered over 30 minutes. The ~4-hour half-life necessitated twice-weekly dosing — a schedule that may have been pharmacokinetically insufficient.
The Pharmacokinetic Question
Post-CENTRIC analysis has focused on whether cilengitide's short half-life created a dosing problem. If effective integrin blockade requires sustained receptor occupancy, twice-weekly IV boluses may produce peak-trough oscillations that alternate between adequate and subtherapeutic exposure. The low-dose stimulation hypothesis suggests that trough-level exposure could paradoxically promote the very angiogenesis the drug was designed to inhibit.
Whether a continuous-infusion or sustained-release formulation could have changed the outcome is unknowable — no such formulation was developed or tested.
Dosing in Published Research
The following table summarizes dosing protocols for Cilengitide as reported in published clinical and preclinical research. These reflect study designs, not treatment recommendations.
Clinical Trial Dosing (Discontinued)
| Parameter | Value |
|---|---|
| Dose | 2,000 mg IV |
| Schedule | Twice weekly (30-minute infusion) |
| Duration | Throughout chemoradiation (6 weeks) and adjuvant temozolomide phase |
| Combination | Standard Stupp regimen (temozolomide + radiotherapy) |
| Half-life | ~4 hours (pharmacokinetic concern regarding sustained target engagement) |
| Setting | Oncology infusion center |
PLAIN ENGLISH
Patients received cilengitide as a 30-minute IV drip twice a week, alongside standard brain tumor treatment. The drug left the body within hours — which may be why it didn't work, though this has never been proven.
Combination Stacks
COMMUNITY-SOURCED INFORMATION
The dosing information below is drawn from community reports, forums, and anecdotal sources — not clinical trials. It reflects what people report using, not what has been validated by research. This is not medical advice.
Research into Cilengitide combination protocols is limited. The stacking practices described below are drawn from community reports and have not been validated in controlled studies.
If you are considering combining Cilengitide with other compounds, consult a qualified healthcare provider. Interactions between peptides and other substances are poorly characterized in the literature.
| Compound | Type | Evidence Tier | Verdict | Primary Mechanism | Target/Receptor | Landmark Trial | Human Data | FDA Status | WADA Status | Key Limitation |
|---|---|---|---|---|---|---|---|---|---|---|
| Octreotide | Cyclic octapeptide SSA (8 aa, disulfide) | Tier 1 — Approved Drug | Strong Foundation | SSTR2/5 agonist → antisecretory + antiproliferative | SSTR2, SSTR5 | PROMID (N=85, TTP HR 0.34) | Phase III RCT; 30+ years clinical use | Approved 1988 (acromegaly, carcinoid, GEP-NETs) | Not prohibited | Gallstones (15–30%); glucose metabolism effects |
| Lanreotide | Cyclic octapeptide SSA (8 aa, disulfide) | Tier 1 — Approved Drug | Strong Foundation | SSTR2/3/5 agonist → antiproliferative in nonfunctioning NETs | SSTR2, SSTR3, SSTR5 | CLARINET (N=204, PFS HR 0.47) | Phase III RCT; 15+ years post-approval | Approved 2007 (acromegaly); 2014 (GEP-NETs) | Not prohibited | Same class as octreotide; gallstones; glucose effects |
| Lutathera | Radiolabeled peptide (¹⁷⁷Lu-DOTATATE) | Tier 1 — Approved Drug | Strong Foundation | SSTR2-targeted PRRT → intracellular beta-radiation → DNA damage | SSTR2 | NETTER-1 (N=229, PFS HR 0.21) | Phase III RCT + 504-pt registry | Approved January 2018 (SSTR+ GEP-NETs) | Not prohibited | Myelosuppression; MDS/AML risk (~2%); requires nuclear medicine facility |
| Motixafortide | Cyclic peptide (14 aa) | Tier 2 — Clinical Trials | Reasonable Bet | CXCR4 antagonist → stem cell mobilization + tumor immune sensitization | CXCR4 | GENESIS (N=122, 92.5% vs. 26.2% mobilization) | Phase III + Phase 2a (N=199 total) | Not approved (Phase 3 complete) | Not prohibited | No FDA approval yet; competes with approved plerixafor |
| Melflufen | Peptide-drug conjugate (dipeptide-melphalan) | Tier 2 — Clinical Trials | Thin Ice | Aminopeptidase-activated intracellular melphalan release → DNA crosslinking | Aminopeptidase N (CD13) | OCEAN (N=495, PFS HR 0.79 but OS HR 1.104) | Phase III RCT (N=652 total) | Approved Feb 2021; WITHDRAWN Feb 2024 | Not prohibited | Worse OS than comparator; severe myelosuppression; market withdrawal |
| Cilengitide | Cyclic RGD pentapeptide (5 aa) | Tier 2 — Clinical Trials | Thin Ice | αvβ3/αvβ5 integrin antagonist → antiangiogenic | αvβ3, αvβ5 integrins | CENTRIC (N=545, OS HR 1.02) | Phase III RCT (N=891 total) | Not approved; development discontinued | Not prohibited | Definitive Phase III failure (HR 1.02); development abandoned |
style="color:#0F4C5C;font-size:28px;font-weight:700;margin:48px 0 16px 0;line-height:1.2">Frequently Asked Questions
What was cilengitide?
Why did cilengitide fail?
Was cilengitide ever FDA-approved?
Is cilengitide still being studied?
Was the preclinical data fraudulent?
Could a different integrin inhibitor work where cilengitide failed?
Does cilengitide's failure mean antiangiogenic therapy doesn't work?
What is the RGD motif?
Was cilengitide safe?
What happened to the patients in the CENTRIC trial?
What lesson does cilengitide teach about peptide drug development?
Is anyone still working on RGD-based cancer therapies?
Summary of Key Findings
Cilengitide is the purest cautionary tale in peptide oncology. Built on legitimate preclinical data, a sound mechanistic hypothesis, and the most studied peptide motif in biology (RGD), it entered a well-designed Phase III trial with 545 patients — and produced a hazard ratio of 1.02 for overall survival. The drug was safe. It simply had no effect on human glioblastoma.
The failure has been attributed to pharmacokinetic insufficiency (short half-life), potential low-dose paradoxical stimulation of angiogenesis, target redundancy in human tumors, and possible overrepresentation of integrin importance in preclinical models. None of these explanations has been definitively confirmed — the most honest conclusion is that the target didn't translate.
Cilengitide's significance for Peptidings readers is its role as a benchmark: whenever a peptide compound's evidence rests primarily on preclinical data, cilengitide is the reminder that preclinical evidence is a hypothesis, not a prediction.
PLAIN ENGLISH
Cilengitide was a peptide designed to stop brain tumors from growing blood vessels. It worked in mice. It failed completely in a trial of 545 people — patients lived the exact same amount of time whether they got the drug or not. The drug wasn't dangerous, just useless. It's the clearest example of why lab results don't always predict what happens in real patients.
Verdict Recapitulation
Cilengitide earned Tier 2 through a completed Phase III program — 545 patients, controlled design, definitive result. The problem is the result: a flat null. The compound is discontinued. The development program is dead. Thin Ice — not because the evidence is weak, but because it definitively points to the absence of benefit.
For readers considering Cilengitide, the evidence above represents the current state of knowledge. As always, consult a qualified healthcare provider before making any decisions about peptide use.
Where to Source Cilengitide
Further Reading and Resources
If you want to go deeper on Cilengitide, the evidence landscape for cancer & oncology peptides, or the methodology behind how we evaluate this research, these are the places worth your time.
ON PEPTIDINGS
- Cancer & Oncology Research Hub — Overview of all compounds in this cluster
- Reconstitution Guide — How to properly prepare injectable peptides
- Storage and Handling Guide — Proper storage to maintain peptide stability
- About Peptidings — Our editorial methodology and evidence framework
EXTERNAL RESOURCES
- PubMed: Cilengitide — All indexed publications
- ClinicalTrials.gov — Active and completed trials
Selected References and Key Studies
- Stupp R, Hegi ME, Gorlia T, et al. (2014). "Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071-22072 study): a multicentre, randomised, open-label, phase 3 trial." Lancet Oncology, 15(10), 1100–1108. PMID 25349218
- Nabors LB, Fink KL, Mikkelsen T, et al. (2015). "Two cilengitide regimens in combination with standard treatment for patients with newly diagnosed glioblastoma and unmethylated MGMT gene promoter (CORE): a randomised, controlled, multicentre, phase 2 trial." Lancet Oncology, 16(7), 822–830. PMID 26124478
- Reardon DA, Fink KL, Mikkelsen T, et al. (2008). "Randomized phase II study of cilengitide, an integrin-targeting arginine-glycine-aspartic acid peptide, in recurrent glioblastoma multiforme." Journal of Clinical Oncology, 26(34), 5610–5617. PMID 18695192
- Desgrosellier JS, Cheresh DA. (2010). "Integrins in cancer: biological implications and therapeutic opportunities." Nature Reviews Cancer, 10(1), 9–22. PMID 20029421
- Reynolds AR, Hart IR, Watson AR, et al. (2009). "Stimulation of tumor growth and angiogenesis by low concentrations of RGD-mimetic integrin inhibitors." Nature Medicine, 15(4), 392–400. PMID 19305414
- Merck Serono. (2014). Discontinuation of cilengitide development program. Press release
DISCLAIMER
Cilengitide is not approved by the FDA for any indication in the United States. The information presented in this article is for educational and research purposes only. Nothing in this article constitutes medical advice, and no material here is intended to diagnose, treat, cure, or prevent any disease or health condition.
Consult a qualified healthcare provider before making any decisions about peptide use. Report adverse events to the FDA via MedWatch.
For the full Peptidings editorial methodology and evidence framework, visit our About page and Evidence Framework pages.
Article last reviewed: April 11, 2026. Next scheduled review: October 08, 2026.