Cilengitide (EMD 121974)_Dosage, benefits & legal status
Also known as EMD 121974, cyclo[RGDf(NMe)V], cilengitide trifluoroacetate, cilengitide hydrochloride, cilengitide mesylate
A rigid ring built around RGD, the three-amino-acid grip point cells use to hold on to their surroundings. It added nothing to survival in glioblastoma (26.3 months in both arms), and development stopped in 2013.
Common vial size is what vendors typically sell, not a recommendation. Enter your own vial in the calculator.
What is Cilengitide (EMD 121974)?
Plain language first. The technical label stays, but it never stands alone.Overview
Cilengitide was designed to block integrins, the surface proteins cells use to grip the material around them, in the hope of cutting off the new blood vessels and spread of brain tumors. In the CENTRIC phase 3, 545 people with newly diagnosed glioblastoma received standard radiotherapy and temozolomide with or without it, and median survival was 26.3 months in both groups. Trials in head and neck, lung and pancreatic cancer were also negative, and it is now sold only as a laboratory chemical, not as a medicine.
Cilengitide is cyclo(-Arg-Gly-Asp-D-Phe-N-methyl-Val-), a head-to-tail cyclic pentapeptide (C27H40N8O7, 588.66 Da) that holds the RGD integrin-recognition motif in a rigid ring; it is the N-methylated derivative of cyclo(-RGDfV-), designed at the Technical University of Munich with Merck KGaA. It occupies the ligand pocket of the alpha-v beta-3 and alpha-v beta-5 integrins on tumor blood-vessel cells and some tumor cells, and binds alpha-5 beta-1 more weakly, with the aim of blocking new vessel growth and tumor invasion. Merck took it through a phase 3 in glioblastoma (CENTRIC), stopped development in 2013 after that trial failed, and it survives only as a laboratory tool compound.
What it's used for
Nothing in medicine. It was tested as an add-on to cancer treatment, mainly for glioblastoma, and is now used only in the lab to block alpha-v integrins.
How does Cilengitide (EMD 121974) work?
What it does in the body, and where.Cilengitide copies the grip point that cells use to hold on to the proteins around them, and blocks the receptors that grab it.
- 01A rigid copy of RGDMatrix proteins such as vitronectin carry a three-amino-acid loop, arginine-glycine-aspartate (RGD), that integrins on the cell surface hold on to. Cilengitide locks RGD into a five-residue ring, with a D-phenylalanine and an N-methylated valine fixing its shape.
- 02Blocking the integrinIt sits in the ligand pocket of alpha-v beta-3 and alpha-v beta-5 integrins, found on the cells of new tumor blood vessels and on some tumor cells, and binds alpha-5 beta-1 more weakly. In the lab, blocked cells lose FAK, Src and AKT survival signaling, then detach and die. The experimental lung peptide ORJ-001 is designed to do the reverse, switching beta-1 integrin on.
- 03What happened in peopleThe aim was to stop new vessel growth and invasion, but in patients it did not extend survival. Its half-life is only 3 to 5 hours, and a 2015 lab paper speculated that twice-weekly infusions may have been suboptimal.
A schematic of the compound's mechanism, not a diagnostic image.
What else is it used for?
Each group carries its own evidence level.Approved means regulators have cleared it for that purpose. Investigational means it is in trials. Early research means it is being studied and is not established.
Glioblastoma, methylated MGMT (CENTRIC phase 3)
tested-and-failed- Human trial545 patients randomized: median overall survival 26.3 months in both arms (HR 1.02, 95% CI 0.81 to 1.29; p=0.86); 56% alive at two years in each.
- Human trialProgression-free survival 13.5 against 10.7 months by investigators (HR 0.93, P=0.46) and 10.6 against 7.9 months by independent review (HR 0.92, P=0.41), neither significant.
- No dataOpen-label and funded by Merck KGaA; the authors concluded it will not be further developed as an anticancer drug.
Glioblastoma, unmethylated MGMT (CORE phase 2)
tested-and-failed- Human trial265 patients: median overall survival 16.3 months on twice-weekly dosing (HR 0.686, P=0.032), 14.5 months on intensive dosing, five times weekly for weeks 1 to 6 and then twice weekly (HR 0.858, P=0.3771) and 13.4 months on standard treatment; progression-free survival 5.6, 5.9 and 4.1 months.
- No dataThe P-values were not adjusted for multiple comparisons, the more intensive arm showed no effect, and no phase 3 confirmed the signal.
Head and neck cancer (ADVANTAGE)
tested-and-failed- Human trial184 patients given cetuximab, cisplatin and 5-FU: median progression-free survival 6.4 months once weekly (HR 1.03, P=0.885) and 5.6 months twice weekly (HR 1.55, P=0.054) against 5.7 months without cilengitide.
- Human trialOverall survival 12.4 and 10.6 against 11.6 months (HR 0.94 and 1.04), with no significant difference; the twice-weekly trend toward harm was in progression-free survival.
Lung cancer (CERTO)
tested-and-failed- Human trial220 randomized to cetuximab plus cisplatin and gemcitabine or vinorelbine: median progression-free survival 6.2 months on once-weekly cilengitide against 5.0 months (HR 0.718, 95% CI 0.492 to 1.048; p=0.0845), and overall survival 13.6 against 9.7 months (HR 0.813, p=0.2648); neither significant.
Pancreatic cancer
tested-and-failed- Human trial89 patients: median overall survival 6.7 months with gemcitabine plus cilengitide against 7.7 months with gemcitabine alone; progression-free survival 3.6 against 3.8 months; response 17% against 14%.
CENTRIC is often reported as run in 23 countries, the figure in Merck's February 25, 2013, release; the Lancet Oncology paper gives 146 sites in 25 countries. The 545 figure counts randomized patients; 3,471 were screened. It is often said that Merck stopped development when CENTRIC failed, but that release did not announce discontinuation and said CORE and a lung cancer trial were still running; the EU orphan designation was withdrawn at Merck's request in March 2013, the last trials were completed in August 2013, and the 2014 paper stated it will not be further developed as an anticancer drug. CORE is sometimes cited as a positive trial, but its twice-weekly survival gain (P=0.032) was nominal, not adjusted for multiple comparisons, absent in the higher-dose arm and never confirmed. The half-life is often quoted as about 4 hours; the phase 1 reported 3 to 5 hours. Potency figures vary by assay: a supplier data sheet lists about 4 nanomolar for alpha-v beta-3 and 79 nanomolar for alpha-v beta-5 in cell-free assays, the original chemistry papers report lower values, and cell-based figures vary further, so no single number is definitive.
The published record
Papers and trials about Cilengitide (EMD 121974)
302 papers tagged human · 202 not reviews or lab · 32 clinical trial publications
30 registered trials · 9 with posted results
Furthest stage reached: Phase 3, results posted
Counted from Europe PMC indexing, not read by a person; a human tag can land on reviews, commentary or lab papers; clinical trial publications is the narrower count. 416 papers and 30 trials indexed in detail.
At a glance
Four things to know about Cilengitide (EMD 121974)
Evidence
Investigational
Category
Longevity and energy
Common vial
Varies
Half-life
About 3 to 5 hours
How much, and do you cycle it?
The range, and whether you take breaks.2,000 mg infused twice weekly with radiotherapy and temozolomide (phase 3 trial), twice weekly (phase 3 trial). Continuous twice-weekly infusions in trials; development ended in 2013 Trial dose
CENTRIC gave it twice weekly from one week before radiotherapy to week 77, through chemoradiation and then temozolomide cycles. No product exists, so there is no schedule to plan around.
How long does it stay in the body?
The half-life, and where the figure comes from.About 3 to 5 hoursHuman study
Terminal half-life after 1-hour infusions in the phase 1, at 30 to 1,600 mg/m2 twice weekly. The pharmacokinetics were dose-independent and did not change over repeated dosing. A 2015 lab paper speculated that, given this short half-life, twice-weekly infusions may have been suboptimal.
Source: Eskens FALM et al., European Journal of Cancer 2003 (phase 1)
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How is it given?
Dosing context and source notes.Given in hospital from a prepared product, so there is nothing to mix.
Trial range: 500 up to 2000 mg per dose. ClinicalTrials.gov, CENTRIC posted results (NCT00689221)
Given into a vein over 1 hour. In CENTRIC and CORE the standard regimen was 2,000 mg twice weekly from one week before radiotherapy to week 77, alongside 60 Gy of radiotherapy in 2 Gy fractions over weeks 1 to 6 with daily temozolomide 75 mg/m2, then temozolomide 150 to 200 mg/m2 on days 1 to 5 every 4 weeks to week 34; CORE also tested an intensive arm of 2,000 mg five times weekly during weeks 1 to 6, then twice weekly. Earlier glioblastoma trials compared 500 mg with 2,000 mg: with chemoradiation in NABTT 0306, and twice weekly on its own in recurrent disease; and the phase 1 gave 30 to 1,600 mg/m2 twice weekly without reaching a maximum tolerated dose. It is not available as a medicine anywhere, only as a research chemical labeled not for human use, so the calculator starts with an empty dose field.
How do you store it?
Before mixing, and after.Given in a hospital or trial clinic, so the pharmacy stores it.
Cilengitide (EMD 121974) goes into a vein and is prepared by hospital, clinic or trial pharmacy staff, following the product label or the trial protocol. Some products like this are ready-made solutions and others are powders mixed just before use, often with hours rather than weeks of shelf life once prepared. It is not a medicine people store at home.
What are the side effects and cautions?
Known cautions and warnings for this compound.Solubility, computed: 80% charged residues, 40% hydrophobic. Water usually sufficient.
A first-pass rule from peptide manufacturers' guidance. It does not account for disulfide bridges, salt form or how the powder was dried, and it predicts what should be easy rather than what will happen in your vial.
Who should avoid it
- Use outside a clinical trial: it was never approved, and the only material sold is labeled for research use, not for people
- Not studied in pregnancy or breastfeeding: no data exist
- Not studied by mouth or under the skin: every trial gave it into a vein
Stop and get help
- A new seizure or sudden weakness on one side of the body: both were more common with cilengitide in the phase 3
- Sudden breathlessness, chest pain or a swollen, painful leg: blood clots were more frequent with cilengitide in the phase 3
Common effects
- Headache in 43.4% against 33.7% and diarrhea in 16.7% against 7.8%, with standard radiotherapy and temozolomide in CENTRIC
- Seizures in 14.1% against 5.4%; serious weakness on one side of the body (hemiparesis) in 4.6% against 0.4%
- Blood clot events in 35 against 23 patients in CENTRIC; in CORE, serious pulmonary embolism in 9 on twice-weekly dosing, 2 on intensive dosing and 1 on standard treatment
- Serious adverse events in 52.5% against 44.6%, treatment-related serious events in 20.9% against 18.2%, and deaths from adverse events in 4.2% against 3.5%
Where this page says nothing is established, that means nobody has studied it, not that a compound is safe.
Is Cilengitide (EMD 121974) approved?
And where the numbers on this page come from.No. Cilengitide (EMD 121974) was never approved, and its development has ended. There is no legal route to obtain it as a medicine.
- Approval statusInvestigational
- RouteInto a vein (1-hour infusion)
- Checked19 October 2026
- DoseFrom published clinical trials. Not approved by a regulator for this dose.
- Vial sizeFrom what vendors typically list; not a recommendation.
- SourcesFDA GSRS substance record, cilengitide (UNII 4EDF46E4GI)Stupp R et al., Lancet Oncology 2014;15:1100-1108 (CENTRIC)ClinicalTrials.gov, CENTRIC posted results (NCT00689221)ClinicalTrials.gov, CORE posted results (NCT00813943)ASCO Post on CENTRIC (October 15, 2014)Merck KGaA, CENTRIC result (Fierce Biotech, February 25, 2013)EMA, orphan designation EU/3/03/184FDA orphan drug designation, cilengitideEskens FALM et al., European Journal of Cancer 2003;39:917-926Chillà et al., Experimental Cell Research 2015;337:68-75ClinicalTrials.gov, ADVANTAGE posted results (NCT00705016)ClinicalTrials.gov, CERTO posted results (NCT00842712)Friess H et al., BMC Cancer 2006;6:285Fierce Biotech on Iceni Pharmaceuticals (May 26, 2016)
What has happened recently
Never approved by the FDA, the EMA or any other agency. Merck KGaA of Darmstadt developed it, with EMD Serono as its US sponsor. The EU granted orphan designation for glioma on January 14, 2004 (EU/3/03/184), and the FDA for malignant glioma on May 27, 2005; both were later withdrawn. The phase 3 CENTRIC (NCT00689221) began in September 2008, after an earlier phase 1/2a study with radiotherapy and temozolomide had suggested benefit in patients with a methylated MGMT promoter compared with historical controls. On February 25, 2013, Merck announced that CENTRIC had missed its primary endpoint of overall survival; that release did not announce an end to development and said CORE and a lung cancer trial were ongoing. The EU orphan designation was withdrawn at Merck's request in March 2013, the remaining trials were completed by August 2013, and the CENTRIC paper, published online on August 19, 2014, stated that cilengitide "will not be further developed as an anticancer drug". In 2016 Iceni Pharmaceuticals of the UK said it would try to repurpose the off-patent compound for multiple myeloma, with a phase 2 planned for 2017 subject to funding; whether that trial took place is not established.
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What else is like Cilengitide (EMD 121974)?
Others in Longevity and energy, side by side.If you're weighing Cilengitide (EMD 121974), it's worth reading MOTS-c, Epitalon, and NAD+ in the same class.
A rigid ring built around RGD, the three-amino-acid grip point cells use to hold on to their surroundings. It added nothing to survival in glioblastoma (26.3 months in both arms), and development stopped in 2013.
- Dose
- 2,000 mg infused twice weekly with radiotherapy and temozolomide (phase 3 trial)
- How often
- Twice weekly (phase 3 trial)
A shot people use for energy, metabolism, and healthy aging.
- Dose
- 1 up to 5 mg per day (start low, increase slowly)
- How often
- Daily
A longevity peptide taken in short courses for sleep and anti-aging.
- Dose
- 5 up to 10 mg per day (start low, increase slowly)
- How often
- 10-20 day courses
A cellular fuel taken for energy, focus, and anti-aging.
- Dose
- 50 up to 100 mg per dose (start low, increase slowly)
- How often
- 2-3x/week
Guides for this compound
- How to Reconstitute a Peptide
Mix peptide powder with bacteriostatic water, step by step.
- How to Read an Insulin Syringe
Read the units, convert to millilitres, and draw the exact dose.
- mcg vs mg: The Peptide Dosing Mistake to Avoid
Your vial says mg and your protocol says mcg. Here is the conversion and how to check it.
- How to Read a Peptide COA
What the purity number does and does not tell you, and how to spot an edited report.
- How to Vet a Peptide Vendor
Independent COAs, HPLC purity, and the red flags that mean walk away.
Sources
- FDA GSRS substance record, cilengitide (UNII 4EDF46E4GI)(2026)Cyclo(L-arginylglycyl-L-alpha-aspartyl-D-phenylalanyl-N-methyl-L-valyl); C27H40N8O7, MW 588.66; CAS 188968-51-6; INN and USAN names.
- Stupp R et al., Lancet Oncology 2014;15:1100-1108 (CENTRIC)(2014)545 patients with methylated MGMT glioblastoma at 146 sites in 25 countries; median overall survival 26.3 months in both arms (HR 1.02, p=0.86).
- ClinicalTrials.gov, CENTRIC posted results (NCT00689221)(2014)Dosing schedule; HR 1.021 (95% CI 0.808 to 1.291); side-effect table for 263 against 258 patients.
- ClinicalTrials.gov, CORE posted results (NCT00813943)(2014)265 patients with unmethylated MGMT glioblastoma; overall survival by arm; serious pulmonary embolism in 9, 2 and 1 patients.
- ASCO Post on CENTRIC (October 15, 2014)(2014)3,471 screened; grade 3 or worse side effects by arm; the authors said it will not be further developed as an anticancer drug.
- Merck KGaA, CENTRIC result (Fierce Biotech, February 25, 2013)(2013)Phase 3 did not meet its primary endpoint; CORE and a lung cancer trial were ongoing; nausea and fatigue most common in earlier studies.
- EMA, orphan designation EU/3/03/184(2013)EU orphan designation for glioma (January 14, 2004), withdrawn at the sponsor's request in March 2013.
- FDA orphan drug designation, cilengitide(2005)Designated May 27, 2005, for malignant glioma (EMD Serono); later withdrawn, and not approved for that use.
- Eskens FALM et al., European Journal of Cancer 2003;39:917-926(2003)Phase 1 in 37 patients: 30 to 1,600 mg/m2 twice weekly, no dose-limiting toxicity, half-life 3 to 5 hours.
- Chillà et al., Experimental Cell Research 2015;337:68-75(2015)Osteoclast lab study; speculates that twice-weekly dosing, given the 3 to 5 hour half-life, was not the most appropriate schedule.
- ClinicalTrials.gov, ADVANTAGE posted results (NCT00705016)(2014)Head and neck cancer, 184 patients: no gain in progression-free survival, with a trend toward harm on twice-weekly dosing.
- ClinicalTrials.gov, CERTO posted results (NCT00842712)(2014)Non-small cell lung cancer, 220 randomized: progression-free survival 6.2 against 5.0 months (p=0.0845), not significant.
- Friess H et al., BMC Cancer 2006;6:285(2006)Pancreatic cancer, 89 patients: median overall survival 6.7 months with cilengitide plus gemcitabine against 7.7 months with gemcitabine alone.
- Fierce Biotech on Iceni Pharmaceuticals (May 26, 2016)(2016)Merck discontinued cilengitide in 2013; Iceni planned to repurpose it for multiple myeloma with proteasome inhibitors.
Beyond these, 446 records are indexed. Browse the records