Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C27H40N8O7.ClH |
| Molecular Weight | 625.117 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 4 / 4 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.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=JSBRBZVFFMRGCI-LOPTWHKWSA-N
InChI=1S/C27H40N8O7.ClH/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);1H/t17-,18-,19+,22-;/m0./s1
| Molecular Formula | C27H40N8O7 |
| Molecular Weight | 588.6559 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 4 / 4 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
| Molecular Formula | ClH |
| Molecular Weight | 36.461 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
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 |
|---|---|---|---|---|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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 |
|
3.51 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 |
|
3.95 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 |
|
3.66 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 |
|
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 |
|
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 |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Cilengitide: the first anti-angiogenic small molecule drug candidate design, synthesis and clinical evaluation. | 2010-12 |
|
| 2010: neuro-oncology is moving! | 2010-12 |
|
| Anti-angiogenic therapies for children with cancer. | 2010-12 |
|
| What role should cilengitide have in the treatment of glioblastoma? | 2010-11-20 |
|
| The potential of nanomedicine therapies to treat neovascular disease in the retina. | 2010-10-08 |
|
| Targeting integrins in malignant glioma. | 2010-09 |
|
| American Association for Cancer Research Genetics and Biology of Brain Cancers 2009, December 13-15, 2009, San Diego, CA. | 2010-09 |
|
| [Angiogenesis inhibition in neurooncology. A very promising therapy strategy for malignant glioma]. | 2010-08 |
|
| Vicrostatin - an anti-invasive multi-integrin targeting chimeric disintegrin with tumor anti-angiogenic and pro-apoptotic activities. | 2010-06-03 |
|
| Phase I/IIa study of cilengitide and temozolomide with concomitant radiotherapy followed by cilengitide and temozolomide maintenance therapy in patients with newly diagnosed glioblastoma. | 2010-06-01 |
|
| Integrins as target: first phase III trial launches, but questions remain. | 2010-05-19 |
|
| Survival of patients with newly diagnosed glioblastoma treated with radiation and temozolomide in research studies in the United States. | 2010-04-15 |
|
| Endothelial-Rac1 is not required for tumor angiogenesis unless alphavbeta3-integrin is absent. | 2010-03-22 |
|
| BCNU for recurrent glioblastoma multiforme: efficacy, toxicity and prognostic factors. | 2010-02-02 |
|
| Integrins in cancer: biological implications and therapeutic opportunities. | 2010-01 |
|
| Interplay between cell adhesion and growth factor receptors: from the plasma membrane to the endosomes. | 2010-01 |
|
| Mesenchymal migration as a therapeutic target in glioblastoma. | 2010 |
|
| Tumor angiogenesis: insights and innovations. | 2010 |
|
| Antiangiogenic therapy and mechanisms of tumor resistance in malignant glioma. | 2010 |
|
| Progress on antiangiogenic therapy for patients with malignant glioma. | 2010 |
|
| New therapies for recurrent glioblastomas. | 2009-12-09 |
|
| Cilengitide modulates attachment and viability of human glioma cells, but not sensitivity to irradiation or temozolomide in vitro. | 2009-12 |
|
| alphavbeta3 Integrin-targeting Arg-Gly-Asp (RGD) peptidomimetics containing oligoethylene glycol (OEG) spacers. | 2009-11-26 |
|
| Pharmacological inhibition of integrin alphavbeta3 aggravates experimental liver fibrosis and suppresses hepatic angiogenesis. | 2009-11 |
|
| Critical appraisal of temozolomide formulations in the treatment of primary brain tumors: patient considerations. | 2009-10-30 |
|
| Small molecule integrin antagonists in cancer therapy. | 2009-10 |
|
| Ligands for mapping alphavbeta3-integrin expression in vivo. | 2009-07-21 |
|
| Will integrin inhibitors have proangiogenic effects in the clinic? | 2009-07 |
|
| Radiation sensitization of glioblastoma by cilengitide has unanticipated schedule-dependency. | 2009-06-01 |
|
| A complex extracellular sphingomyelinase of Pseudomonas aeruginosa inhibits angiogenesis by selective cytotoxicity to endothelial cells. | 2009-05 |
|
| Cilengitide: does it really represent a new targeted therapy for recurrent glioblastoma? | 2009-04-10 |
|
| Targeted therapy in the treatment of malignant gliomas. | 2009-02-18 |
|
| 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: a new weapon against glioblastoma?]. | 2008-12-31 |
|
| Cilengitide induces cellular detachment and apoptosis in endothelial and glioma cells mediated by inhibition of FAK/src/AKT pathway. | 2008-12-29 |
|
| Randomized phase II study of cilengitide, an integrin-targeting arginine-glycine-aspartic acid peptide, in recurrent glioblastoma multiforme. | 2008-12-01 |
|
| Valproic acid related idiosyncratic drug induced hepatotoxicity in a glioblastoma patient treated with temozolomide. | 2008-12 |
|
| Therapeutic application of noncytotoxic molecular targeted therapy in gliomas: growth factor receptors and angiogenesis inhibitors. | 2008-09 |
|
| Novel therapies in genitourinary cancer: an update. | 2008-08-11 |
|
| Cilengitide: an integrin-targeting arginine-glycine-aspartic acid peptide with promising activity for glioblastoma multiforme. | 2008-08 |
|
| Oncolytic HSV-1 infection of tumors induces angiogenesis and upregulates CYR61. | 2008-08 |
|
| In vitro sensitivity testing of minimally passaged and uncultured gliomas with TRAIL and/or chemotherapy drugs. | 2008-07-22 |
|
| Gateways to clinical trials. | 2008-05 |
|
| The role of integrins in cancer and the development of anti-integrin therapeutic agents for cancer therapy. | 2008-04-10 |
|
| Surgical impact on brain tumor invasion: a physical perspective. | 2008-04-02 |
|
| The integrin antagonist cilengitide increases the antitumor activity of temozolomide against malignant melanoma. | 2008-04 |
|
| Phase I clinical trial of cilengitide in children with refractory brain tumors: Pediatric Brain Tumor Consortium Study PBTC-012. | 2008-02-20 |
|
| 2007 EORTC-NCI-ASCO annual meeting: molecular markers in cancer. | 2008 |
|
| Tumor angiogenic endothelial cell targeting by a novel integrin-targeted nanoparticle. | 2007 |
Patents
Sample Use Guides
500 or 2000 mg infusions of cilengitide twice weekly for up to 48 weeks
Route of Administration:
Intravenous
| Substance Class |
Chemical
Created
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admin
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Edited
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| Record UNII |
SW9AYG2XI2
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| Record Status |
Validated (UNII)
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