cilengitide   Click here for help

GtoPdb Ligand ID: 6597

Synonyms: EMD-12192 | EMD-121974
Compound class: Peptide
Comment: Cilengitide is a cyclic RGD pentapeptide, first-in-class integrin inhibitor. It inhibits integrin αv-induced angiogenesis. It was investigated for anti-tumour activity. Glioblastoma was one of the cancers investigated [6], based on encouraging preclinical studies in animals [3-4,7].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES OC(=O)CC1NC(=O)CNC(=O)C(CCCNC(=N)N)NC(=O)C(N(C(=O)C(NC1=O)Cc1ccccc1)C)C(C)C
Isomeric SMILES OC(=O)C[C@@H]1NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](N(C(=O)[C@H](NC1=O)Cc1ccccc1)C)C(C)C
InChI 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
InChI Key AMLYAMJWYAIXIA-VWNVYAMZSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Goodman SL, Hölzemann G, Sulyok GA, Kessler H. (2002)
Nanomolar small molecule inhibitors for alphav(beta)6, alphav(beta)5, and alphav(beta)3 integrins.
J Med Chem, 45 (5): 1045-51. [PMID:11855984]
2. Kim KB, Prieto V, Joseph RW, Diwan AH, Gallick GE, Papadopoulos NE, Bedikian AY, Camacho LH, Hwu P, Ng CS et al.. (2012)
A randomized phase II study of cilengitide (EMD 121974) in patients with metastatic melanoma.
Melanoma Res, 22 (4): 294-301. [PMID:22668797]
3. MacDonald TJ, Taga T, Shimada H, Tabrizi P, Zlokovic BV, Cheresh DA, Laug WE. (2001)
Preferential susceptibility of brain tumors to the antiangiogenic effects of an alpha(v) integrin antagonist.
Neurosurgery, 48 (1): 151-7. [PMID:11152340]
4. Mikkelsen T, Brodie C, Finniss S, Berens ME, Rennert JL, Nelson K, Lemke N, Brown SL, Hahn D, Neuteboom B et al.. (2009)
Radiation sensitization of glioblastoma by cilengitide has unanticipated schedule-dependency.
Int J Cancer, 124 (11): 2719-27. [PMID:19199360]
5. Stupp R, Hegi ME, Gorlia T, Erridge SC, Perry J, Hong YK, Aldape KD, Lhermitte B, Pietsch T, Grujicic D et al.. (2014)
Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071-22072 study): a multicentre, randomised, open-label, phase 3 trial.
Lancet Oncol, 15 (10): 1100-8. [PMID:25163906]
6. Weller M, Nabors LB, Gorlia T, Leske H, Rushing E, Bady P, Hicking C, Perry J, Hong YK, Roth P et al.. (2016)
Cilengitide in newly diagnosed glioblastoma: biomarker expression and outcome.
Oncotarget, 7 (12): 15018-32. [PMID:26918452]
7. Yamada S, Bu XY, Khankaldyyan V, Gonzales-Gomez I, McComb JG, Laug WE. (2006)
Effect of the angiogenesis inhibitor Cilengitide (EMD 121974) on glioblastoma growth in nude mice.
Neurosurgery, 59 (6): 1304-12; discussion 1312. [PMID:17277694]