Cilengitide mesylate

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C27H40N8O7.CH4O3S
Molecular Weight	684.762
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CS(O)(=O)=O.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=PMURMRGEABAIKC-LOPTWHKWSA-N

InChI=1S/C27H40N8O7.CH4O3S/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;1-5(2,3)4/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);1H3,(H,2,3,4)/t17-,18-,19+,22-;/m0./s1

HIDE SMILES / InChI

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	CH4O3S
Molecular Weight	96.106
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://ar.iiarjournals.org/content/32/10/4213.full.pdf+html
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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Integrin alpha-V/beta-3 9 Target ID: CHEMBL1907598 Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3411133/pdf/10.1177_1947601912450586.pdf	Antagonist 2849		4.1 nM [IC50]
Integrin alpha-V/beta-5 5 Target ID: CHEMBL2096675 Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3411133/pdf/10.1177_1947601912450586.pdf	Antagonist 2849		79.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Glioblastoma 66 Sources: http://ar.iiarjournals.org/content/32/10/4213.full.pdf+html	Primary		Phase III 665	Unknown Approved Use Unknown

C_max

Value	Dose	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	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

T_1/2

Value	Dose	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

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: https://pubmed.ncbi.nlm.nih.gov/12706360/	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/12706360/	Sources: https://pubmed.ncbi.nlm.nih.gov/12706360/

PubMed

Title	Date	PubMed
Cilengitide: the first anti-angiogenic small molecule drug candidate design, synthesis and clinical evaluation.	2010-12	21269250
2010: neuro-oncology is moving!	2010-12	21051962
Anti-angiogenic therapies for children with cancer.	2010-12	20718702
What role should cilengitide have in the treatment of glioblastoma?	2010-11-20	20975074
The potential of nanomedicine therapies to treat neovascular disease in the retina.	2010-10-08	20932321
Targeting integrins in malignant glioma.	2010-09	20820929
American Association for Cancer Research Genetics and Biology of Brain Cancers 2009, December 13-15, 2009, San Diego, CA.	2010-09	20714783
[Angiogenesis inhibition in neurooncology. A very promising therapy strategy for malignant glioma].	2010-08	20669004
Vicrostatin - an anti-invasive multi-integrin targeting chimeric disintegrin with tumor anti-angiogenic and pro-apoptotic activities.	2010-06-03	20532165
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	20439646
Integrins as target: first phase III trial launches, but questions remain.	2010-05-19	20460633
Survival of patients with newly diagnosed glioblastoma treated with radiation and temozolomide in research studies in the United States.	2010-04-15	20371685
Endothelial-Rac1 is not required for tumor angiogenesis unless alphavbeta3-integrin is absent.	2010-03-22	20339539
BCNU for recurrent glioblastoma multiforme: efficacy, toxicity and prognostic factors.	2010-02-02	20122270
Integrins in cancer: biological implications and therapeutic opportunities.	2010-01	20029421
Interplay between cell adhesion and growth factor receptors: from the plasma membrane to the endosomes.	2010-01	19722108
Mesenchymal migration as a therapeutic target in glioblastoma.	2010	20652056
Tumor angiogenesis: insights and innovations.	2010	20445741
Antiangiogenic therapy and mechanisms of tumor resistance in malignant glioma.	2010	20414333
Progress on antiangiogenic therapy for patients with malignant glioma.	2010	20379377
New therapies for recurrent glioblastomas.	2009-12-09	20948683
Cilengitide modulates attachment and viability of human glioma cells, but not sensitivity to irradiation or temozolomide in vitro.	2009-12	19221171
alphavbeta3 Integrin-targeting Arg-Gly-Asp (RGD) peptidomimetics containing oligoethylene glycol (OEG) spacers.	2009-11-26	19860432
Pharmacological inhibition of integrin alphavbeta3 aggravates experimental liver fibrosis and suppresses hepatic angiogenesis.	2009-11	19725105
Critical appraisal of temozolomide formulations in the treatment of primary brain tumors: patient considerations.	2009-10-30	21188132
Small molecule integrin antagonists in cancer therapy.	2009-10	19929817
Ligands for mapping alphavbeta3-integrin expression in vivo.	2009-07-21	19489579
Will integrin inhibitors have proangiogenic effects in the clinic?	2009-07	19584855
Radiation sensitization of glioblastoma by cilengitide has unanticipated schedule-dependency.	2009-06-01	19199360
A complex extracellular sphingomyelinase of Pseudomonas aeruginosa inhibits angiogenesis by selective cytotoxicity to endothelial cells.	2009-05	19424430
Cilengitide: does it really represent a new targeted therapy for recurrent glioblastoma?	2009-04-10	19255301
Targeted therapy in the treatment of malignant gliomas.	2009-02-18	20616900
Current available therapies and future directions in the treatment of malignant gliomas.	2009	19707392
The integrin antagonist cilengitide activates alphaVbeta3, disrupts VE-cadherin localization at cell junctions and enhances permeability in endothelial cells.	2009	19212436
[Cilengitide: a new weapon against glioblastoma?].	2008-12-31	19112962
Cilengitide induces cellular detachment and apoptosis in endothelial and glioma cells mediated by inhibition of FAK/src/AKT pathway.	2008-12-29	19114005
Randomized phase II study of cilengitide, an integrin-targeting arginine-glycine-aspartic acid peptide, in recurrent glioblastoma multiforme.	2008-12-01	18981465
Valproic acid related idiosyncratic drug induced hepatotoxicity in a glioblastoma patient treated with temozolomide.	2008-12	19239041
Therapeutic application of noncytotoxic molecular targeted therapy in gliomas: growth factor receptors and angiogenesis inhibitors.	2008-09	18779539
Novel therapies in genitourinary cancer: an update.	2008-08-11	18694493
Cilengitide: an integrin-targeting arginine-glycine-aspartic acid peptide with promising activity for glioblastoma multiforme.	2008-08	18616418
Oncolytic HSV-1 infection of tumors induces angiogenesis and upregulates CYR61.	2008-08	18545226
In vitro sensitivity testing of minimally passaged and uncultured gliomas with TRAIL and/or chemotherapy drugs.	2008-07-22	18594532
Gateways to clinical trials.	2008-05	18773127
The role of integrins in cancer and the development of anti-integrin therapeutic agents for cancer therapy.	2008-04-10	19787098
Surgical impact on brain tumor invasion: a physical perspective.	2008-04-02	18384681
The integrin antagonist cilengitide increases the antitumor activity of temozolomide against malignant melanoma.	2008-04	18357394
Phase I clinical trial of cilengitide in children with refractory brain tumors: Pediatric Brain Tumor Consortium Study PBTC-012.	2008-02-20	18281665
2007 EORTC-NCI-ASCO annual meeting: molecular markers in cancer.	2008	22275966
Tumor angiogenic endothelial cell targeting by a novel integrin-targeted nanoparticle.	2007	18019845

Patents

Sample Use Guides

In Vivo Use Guide

500 or 2000 mg infusions of cilengitide twice weekly for up to 48 weeks

Route of Administration: Intravenous

In Vitro Use Guide

25 ug/mL Cilengitide causes detachment of DAOY cells (medulloblastoma) and U87MG cells (glioblastoma) from vitronectin and tenascin by more than 60%. 25 ug/mL Cilengitide induces a nearly 50% apoptosis rate of these cells.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 22:35:18 GMT 2025` Edited by `admin` on `Mon Mar 31 22:35:18 GMT 2025`
Record UNII	NMS4YK4WUH
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

Cilengitide methanesulfonate

Preferred Name

English

Cilengitide mesylate

Common Name

English

Cyclo(L-arginylglycyl-L-?-aspartyl-D-phenylalanyl-N-methyl-L-valyl), methanesulfonate (1:1)

Systematic Name

English

Cyclo(L-arginylglycyl-L-?-aspartyl-D-phenylalanyl-N-methyl-L-valyl), monomethanesulfonate

Systematic Name

English

Code System Code Type Description

PUBCHEM

91827703

Created by admin on Mon Mar 31 22:35:18 GMT 2025 , Edited by admin on Mon Mar 31 22:35:18 GMT 2025

PRIMARY

CAS

199807-38-0

Created by admin on Mon Mar 31 22:35:18 GMT 2025 , Edited by admin on Mon Mar 31 22:35:18 GMT 2025

PRIMARY

FDA UNII

NMS4YK4WUH

Created by admin on Mon Mar 31 22:35:18 GMT 2025 , Edited by admin on Mon Mar 31 22:35:18 GMT 2025

PRIMARY

Related Record Type Details


					4EDF46E4GI

CILENGITIDE

PARENT -> SALT/SOLVATE

Amount:

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					4EDF46E4GI

CILENGITIDE

ACTIVE MOIETY

Amount:

Details

SMILES

InChI

DescriptionSources: http://ar.iiarjournals.org/content/32/10/4213.full.pdf+htmlCurator's Comment: Description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3086618/pdf/thnov01p0154.pdf

CNS Activity

Originator

Approval Year

Targets

Conditions

Approved Use

Cmax

AUC

T1/2

Doses

PubMed

Patents

Sample Use Guides

Description
Sources: http://ar.iiarjournals.org/content/32/10/4213.full.pdf+html
Curator's Comment: Description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3086618/pdf/thnov01p0154.pdf

C_max

T_1/2