Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C27H40N8O7 |
| Molecular Weight | 588.6559 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 4 / 4 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(C)[C@@H]1N(C)C(=O)[C@@H](CC2=CC=CC=C2)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CCCNC(N)=N)NC1=O
InChI
InChIKey=AMLYAMJWYAIXIA-VWNVYAMZSA-N
InChI=1S/C27H40N8O7/c1-15(2)22-25(41)33-17(10-7-11-30-27(28)29)23(39)31-14-20(36)32-18(13-21(37)38)24(40)34-19(26(42)35(22)3)12-16-8-5-4-6-9-16/h4-6,8-9,15,17-19,22H,7,10-14H2,1-3H3,(H,31,39)(H,32,36)(H,33,41)(H,34,40)(H,37,38)(H4,28,29,30)/t17-,18-,19+,22-/m0/s1
DescriptionCurator's Comment: Description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3086618/pdf/thnov01p0154.pdf
Curator's Comment: Description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3086618/pdf/thnov01p0154.pdf
Cilengitide is a cyclized Arg-Gly-Glu (RGD)-containing pentapeptide that selectively blocks activation of the αvβ3 and αvβ5 integrins. Its precursor was first synthesized in 1995 as c(RGDfV), and later modified by the incorporation of N-methyl Val c(RGDfMetV), generating the current form of the drug. Cilengitide displays subnanomolar antagonistic activity for αvβ3 and αvβ5, and is the first integrin antagonist evaluated in clinical phase I and II trials for treatment of glioblastoma and several other tumor types. Cilengitide-induced glioma cell death and inhibition of blood vessel formation may use different molecular mechanisms, including regulation of tumor hypoxia and activation of apoptotic pathways. Cilengitide inhibits cell signaling through FAK-Src-Akt and Erk mediated pathways in endothelial and tumor cells and attenuates the effect of VEGF stimulation on growth factor signaling. Cilengitide has shown encouraging activity in patients with glioblastoma as single agent, and in association with standard RT and temozolomide.
Originator
Sources: http://www.medkoo.com/products/4620
Curator's Comment: # Designed and synthesized at the Technical University Munich in collaboration with Merck KGaA in Darmstadt
Approval Year
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
3334 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12706360/ |
30 mg/m² 2 times / week multiple, intravenous dose: 30 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
CILENGITIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
43418 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12706360/ |
400 mg/m² 2 times / week multiple, intravenous dose: 400 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
CILENGITIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
59487 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12706360/ |
600 mg/m² 2 times / week multiple, intravenous dose: 600 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
CILENGITIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
11101 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12706360/ |
120 mg/m² 2 times / week multiple, intravenous dose: 120 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
CILENGITIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
161619 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12706360/ |
1600 mg/m² 2 times / week multiple, intravenous dose: 1600 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
CILENGITIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
123902 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12706360/ |
1200 mg/m² 2 times / week multiple, intravenous dose: 1200 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
CILENGITIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
11533 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12706360/ |
30 mg/m² 2 times / week multiple, intravenous dose: 30 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
CILENGITIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
161051 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12706360/ |
400 mg/m² 2 times / week multiple, intravenous dose: 400 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
CILENGITIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
168674 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12706360/ |
600 mg/m² 2 times / week multiple, intravenous dose: 600 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
CILENGITIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
32406 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12706360/ |
120 mg/m² 2 times / week multiple, intravenous dose: 120 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
CILENGITIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
521472 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12706360/ |
1600 mg/m² 2 times / week multiple, intravenous dose: 1600 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
CILENGITIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
524688 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12706360/ |
1200 mg/m² 2 times / week multiple, intravenous dose: 1200 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
CILENGITIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
3.51 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12706360/ |
30 mg/m² 2 times / week multiple, intravenous dose: 30 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
CILENGITIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
3.66 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12706360/ |
400 mg/m² 2 times / week multiple, intravenous dose: 400 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
CILENGITIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
3.56 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12706360/ |
600 mg/m² 2 times / week multiple, intravenous dose: 600 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
CILENGITIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
3.95 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12706360/ |
120 mg/m² 2 times / week multiple, intravenous dose: 120 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
CILENGITIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
3.14 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12706360/ |
1600 mg/m² 2 times / week multiple, intravenous dose: 1600 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
CILENGITIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
4.48 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12706360/ |
1200 mg/m² 2 times / week multiple, intravenous dose: 1200 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
CILENGITIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
1600 mg/m2 2 times / week multiple, intravenous Highest studied dose Dose: 1600 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 1600 mg/m2, 2 times / week Sources: |
unhealthy n = 6 Health Status: unhealthy Condition: advanced solid tumours Sex: M+F Food Status: UNKNOWN Population Size: 6 Sources: |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Cilengitide targeting of alpha(v)beta(3) integrin receptor synergizes with radioimmunotherapy to increase efficacy and apoptosis in breast cancer xenografts. | 2002 Aug 1 |
|
| Nanomolar small molecule inhibitors for alphav(beta)6, alphav(beta)5, and alphav(beta)3 integrins. | 2002 Feb 28 |
|
| Gateways to clinical trials. | 2003 Jan-Feb |
|
| Cilengitide Merck. | 2003 Jun |
|
| Alpha v integrin inhibitors and cancer therapy. | 2003 Jun |
|
| Clinical trials referral resource. Current clinical trials of cilengitide, an alpha(v) antagonist in clinical development as an anticancer agent. | 2004 Dec |
|
| Cilengitide (EMD 121974) arrests the growth of a heavily pretreated highly vascularised head and neck tumour. | 2004 Feb |
|
| [Inhibition of cellular adhesion and invasion in gliomas]. | 2005 Sep |
|
| Effect of the angiogenesis inhibitor Cilengitide (EMD 121974) on glioblastoma growth in nude mice. | 2006 Dec |
|
| A randomized multi-center phase II trial of the angiogenesis inhibitor Cilengitide (EMD 121974) and gemcitabine compared with gemcitabine alone in advanced unresectable pancreatic cancer. | 2006 Dec 11 |
|
| Phase II evaluations of cilengitide in asymptomatic patients with androgen-independent prostate cancer: scientific rationale and study design. | 2006 Mar |
|
| Anti-angiogenic cancer therapy based on integrin alphavbeta3 antagonism. | 2006 Sep |
|
| Gateways to clinical trials. | 2007 Jul-Aug |
|
| Cilengitide inhibits proliferation and differentiation of human endothelial progenitor cells in vitro. | 2007 Jun 15 |
|
| Integrin inhibitors reaching the clinic. | 2007 May 1 |
|
| Diffuse glioma growth: a guerilla war. | 2007 Nov |
|
| Chemoradiotherapy in malignant glioma: standard of care and future directions. | 2007 Sep 10 |
|
| 2007 EORTC-NCI-ASCO annual meeting: molecular markers in cancer. | 2008 |
|
| The integrin antagonist cilengitide increases the antitumor activity of temozolomide against malignant melanoma. | 2008 Apr |
|
| The role of integrins in cancer and the development of anti-integrin therapeutic agents for cancer therapy. | 2008 Apr 10 |
|
| Randomized phase II study of cilengitide, an integrin-targeting arginine-glycine-aspartic acid peptide, in recurrent glioblastoma multiforme. | 2008 Dec 1 |
|
| Cilengitide induces cellular detachment and apoptosis in endothelial and glioma cells mediated by inhibition of FAK/src/AKT pathway. | 2008 Dec 29 |
|
| Phase I clinical trial of cilengitide in children with refractory brain tumors: Pediatric Brain Tumor Consortium Study PBTC-012. | 2008 Feb 20 |
|
| In vitro sensitivity testing of minimally passaged and uncultured gliomas with TRAIL and/or chemotherapy drugs. | 2008 Jul 22 |
|
| Gateways to clinical trials. | 2008 May |
|
| Therapeutic application of noncytotoxic molecular targeted therapy in gliomas: growth factor receptors and angiogenesis inhibitors. | 2008 Sep |
|
| [Cilengitide: a new weapon against glioblastoma?]. | 2008 Sep-Oct |
|
| Current available therapies and future directions in the treatment of malignant gliomas. | 2009 |
|
| The integrin antagonist cilengitide activates alphaVbeta3, disrupts VE-cadherin localization at cell junctions and enhances permeability in endothelial cells. | 2009 |
|
| Cilengitide modulates attachment and viability of human glioma cells, but not sensitivity to irradiation or temozolomide in vitro. | 2009 Dec |
|
| Will integrin inhibitors have proangiogenic effects in the clinic? | 2009 Jul |
|
| Radiation sensitization of glioblastoma by cilengitide has unanticipated schedule-dependency. | 2009 Jun 1 |
|
| Critical appraisal of temozolomide formulations in the treatment of primary brain tumors: patient considerations. | 2009 Oct 30 |
|
| Mesenchymal migration as a therapeutic target in glioblastoma. | 2010 |
|
| Tumor angiogenesis: insights and innovations. | 2010 |
|
| Progress on antiangiogenic therapy for patients with malignant glioma. | 2010 |
|
| Survival of patients with newly diagnosed glioblastoma treated with radiation and temozolomide in research studies in the United States. | 2010 Apr 15 |
|
| Cilengitide: the first anti-angiogenic small molecule drug candidate design, synthesis and clinical evaluation. | 2010 Dec |
|
| BCNU for recurrent glioblastoma multiforme: efficacy, toxicity and prognostic factors. | 2010 Feb 2 |
|
| Integrins in cancer: biological implications and therapeutic opportunities. | 2010 Jan |
|
| Interplay between cell adhesion and growth factor receptors: from the plasma membrane to the endosomes. | 2010 Jan |
|
| Phase I/IIa study of cilengitide and temozolomide with concomitant radiotherapy followed by cilengitide and temozolomide maintenance therapy in patients with newly diagnosed glioblastoma. | 2010 Jun 1 |
|
| Endothelial-Rac1 is not required for tumor angiogenesis unless alphavbeta3-integrin is absent. | 2010 Mar 22 |
|
| What role should cilengitide have in the treatment of glioblastoma? | 2010 Nov 20 |
|
| The potential of nanomedicine therapies to treat neovascular disease in the retina. | 2010 Oct 8 |
Patents
Sample Use Guides
500 or 2000 mg infusions of cilengitide twice weekly for up to 48 weeks
Route of Administration:
Intravenous
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EU-Orphan Drug |
EU/3/03/184
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NCI_THESAURUS |
C2144
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FDA ORPHAN DRUG |
205205
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176873
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188968-51-6
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C1834
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CHEMBL429876
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C422910
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NN-20
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SUB25402
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100000089412
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7823
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m3546
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CILENGITIDE
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4EDF46E4GI
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DTXSID9044035
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DB11890
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ACTIVE MOIETY
SALT/SOLVATE (PARENT)
