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 |
|---|---|---|
| Phase I and correlative biology study of cilengitide in patients with recurrent malignant glioma. | 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 |
|
| Cilengitide: an integrin-targeting arginine-glycine-aspartic acid peptide with promising activity for glioblastoma multiforme. | 2008 Aug |
|
| Oncolytic HSV-1 infection of tumors induces angiogenesis and upregulates CYR61. | 2008 Aug |
|
| Novel therapies in genitourinary cancer: an update. | 2008 Aug 11 |
|
| Valproic acid related idiosyncratic drug induced hepatotoxicity in a glioblastoma patient treated with temozolomide. | 2008 Dec |
|
| 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 |
|
| 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: does it really represent a new targeted therapy for recurrent glioblastoma? | 2009 Apr 10 |
|
| Cilengitide modulates attachment and viability of human glioma cells, but not sensitivity to irradiation or temozolomide in vitro. | 2009 Dec |
|
| New therapies for recurrent glioblastomas. | 2009 Dec 9 |
|
| Targeted therapy in the treatment of malignant gliomas. | 2009 Feb 18 |
|
| Will integrin inhibitors have proangiogenic effects in the clinic? | 2009 Jul |
|
| Ligands for mapping alphavbeta3-integrin expression in vivo. | 2009 Jul 21 |
|
| Radiation sensitization of glioblastoma by cilengitide has unanticipated schedule-dependency. | 2009 Jun 1 |
|
| A complex extracellular sphingomyelinase of Pseudomonas aeruginosa inhibits angiogenesis by selective cytotoxicity to endothelial cells. | 2009 May |
|
| Pharmacological inhibition of integrin alphavbeta3 aggravates experimental liver fibrosis and suppresses hepatic angiogenesis. | 2009 Nov |
|
| alphavbeta3 Integrin-targeting Arg-Gly-Asp (RGD) peptidomimetics containing oligoethylene glycol (OEG) spacers. | 2009 Nov 26 |
|
| Small molecule integrin antagonists in cancer therapy. | 2009 Oct |
|
| 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 |
|
| Antiangiogenic therapy and mechanisms of tumor resistance in malignant glioma. | 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 |
|
| [Angiogenesis inhibition in neurooncology. A very promising therapy strategy for malignant glioma]. | 2010 Aug |
|
| Cilengitide: the first anti-angiogenic small molecule drug candidate design, synthesis and clinical evaluation. | 2010 Dec |
|
| 2010: neuro-oncology is moving! | 2010 Dec |
|
| Anti-angiogenic therapies for children with cancer. | 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 |
|
| Vicrostatin - an anti-invasive multi-integrin targeting chimeric disintegrin with tumor anti-angiogenic and pro-apoptotic activities. | 2010 Jun 3 |
|
| Endothelial-Rac1 is not required for tumor angiogenesis unless alphavbeta3-integrin is absent. | 2010 Mar 22 |
|
| Integrins as target: first phase III trial launches, but questions remain. | 2010 May 19 |
|
| 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 |
|
| Targeting integrins in malignant glioma. | 2010 Sep |
|
| American Association for Cancer Research Genetics and Biology of Brain Cancers 2009, December 13-15, 2009, San Diego, CA. | 2010 Sep |
Patents
Sample Use Guides
500 or 2000 mg infusions of cilengitide twice weekly for up to 48 weeks
Route of Administration:
Intravenous
| Name | Type | Language | ||
|---|---|---|---|---|
|
Official Name | English | ||
|
Code | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English |
| Classification Tree | Code System | Code | ||
|---|---|---|---|---|
|
EU-Orphan Drug |
EU/3/03/184
Created by
admin on Sat Dec 16 16:22:49 GMT 2023 , Edited by admin on Sat Dec 16 16:22:49 GMT 2023
|
||
|
NCI_THESAURUS |
C2144
Created by
admin on Sat Dec 16 16:22:49 GMT 2023 , Edited by admin on Sat Dec 16 16:22:49 GMT 2023
|
||
|
FDA ORPHAN DRUG |
205205
Created by
admin on Sat Dec 16 16:22:49 GMT 2023 , Edited by admin on Sat Dec 16 16:22:49 GMT 2023
|
| Code System | Code | Type | Description | ||
|---|---|---|---|---|---|
|
176873
Created by
admin on Sat Dec 16 16:22:49 GMT 2023 , Edited by admin on Sat Dec 16 16:22:49 GMT 2023
|
PRIMARY | |||
|
188968-51-6
Created by
admin on Sat Dec 16 16:22:49 GMT 2023 , Edited by admin on Sat Dec 16 16:22:49 GMT 2023
|
PRIMARY | |||
|
C1834
Created by
admin on Sat Dec 16 16:22:49 GMT 2023 , Edited by admin on Sat Dec 16 16:22:49 GMT 2023
|
PRIMARY | |||
|
CHEMBL429876
Created by
admin on Sat Dec 16 16:22:49 GMT 2023 , Edited by admin on Sat Dec 16 16:22:49 GMT 2023
|
PRIMARY | |||
|
C422910
Created by
admin on Sat Dec 16 16:22:49 GMT 2023 , Edited by admin on Sat Dec 16 16:22:49 GMT 2023
|
PRIMARY | |||
|
NN-20
Created by
admin on Sat Dec 16 16:22:49 GMT 2023 , Edited by admin on Sat Dec 16 16:22:49 GMT 2023
|
PRIMARY | |||
|
SUB25402
Created by
admin on Sat Dec 16 16:22:49 GMT 2023 , Edited by admin on Sat Dec 16 16:22:49 GMT 2023
|
PRIMARY | |||
|
100000089412
Created by
admin on Sat Dec 16 16:22:49 GMT 2023 , Edited by admin on Sat Dec 16 16:22:49 GMT 2023
|
PRIMARY | |||
|
7823
Created by
admin on Sat Dec 16 16:22:49 GMT 2023 , Edited by admin on Sat Dec 16 16:22:49 GMT 2023
|
PRIMARY | |||
|
m3546
Created by
admin on Sat Dec 16 16:22:49 GMT 2023 , Edited by admin on Sat Dec 16 16:22:49 GMT 2023
|
PRIMARY | Merck Index | ||
|
CILENGITIDE
Created by
admin on Sat Dec 16 16:22:49 GMT 2023 , Edited by admin on Sat Dec 16 16:22:49 GMT 2023
|
PRIMARY | |||
|
4EDF46E4GI
Created by
admin on Sat Dec 16 16:22:49 GMT 2023 , Edited by admin on Sat Dec 16 16:22:49 GMT 2023
|
PRIMARY | |||
|
DTXSID9044035
Created by
admin on Sat Dec 16 16:22:49 GMT 2023 , Edited by admin on Sat Dec 16 16:22:49 GMT 2023
|
PRIMARY | |||
|
DB11890
Created by
admin on Sat Dec 16 16:22:49 GMT 2023 , Edited by admin on Sat Dec 16 16:22:49 GMT 2023
|
PRIMARY |
ACTIVE MOIETY
SALT/SOLVATE (PARENT)
