Cilengitide

Cilengitide
Names
	IUPAC name 2-[(2S,5R,8S,11S)-5-benzyl-11-{3-[(diaminomethylidene)amino]propyl}-7-methyl-3,6,9,12,15-pentaoxo-8-(propan-2-yl)-1,4,7,10,13-pentaazacyclopentadecan-2-yl]acetic acid
Identifiers
CAS Number	188968-51-6 ;
3D model (JSmol)	Interactive image;
ChEMBL	ChEMBL429876 ;
ChemSpider	154046 ;
IUPHAR/BPS	6597;
KEGG	D03497 ;
MeSH	Cilengitide
PubChem CID	176873;
UNII	4EDF46E4GI ;
CompTox Dashboard (EPA)	DTXSID9044035 ;
	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 Key: AMLYAMJWYAIXIA-VWNVYAMZSA-N ; InChI=1/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 Key: AMLYAMJWYAIXIA-VWNVYAMZBF;
	SMILES O=C1N[C@H](C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](C(=O)N(C)[C@H]1C(C)C)Cc2ccccc2)CC(=O)O)CCC/N=C(\N)N;
Properties
Chemical formula	C27H40N8O7
Molar mass	588.656 g/mol
Density	1.417 g/mL
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). verify (what is ?) Infobox references

Cilengitide (EMD 121974) is a molecule designed and synthesized at the Technical University Munich in collaboration with Merck KGaA in Darmstadt. It is based on the cyclic peptide cyclo(-RGDfV-), which is selective for α_v integrins, which are important in angiogenesis (forming new blood vessels), and other aspects of tumor biology. Hence, it is under investigation for the treatment of glioblastoma, where it may act by inhibiting angiogenesis, and influencing tumor invasion and proliferation.^[1]^[2]

The European Medicines Agency has granted cilengitide orphan drug status.^[3]

Cilengitide seems to function by inhibiting the FAK/Src/AKT pathway and inducing apoptosis in endothelial cells.^[4] Preclinical studies in mice of cilengitide were able to demonstrate efficacious tumor regression.^[4]

In a rat xenograft model, cilengitide was able to potentiate the cytotoxic effects of radiation when cilengitide was administered prior to radiation therapy.^[5] When combined with radiation, inhibition of integrin expression by cilengitide synergistically improves the cytotoxic effects of ionizing radiation for glioblastoma.^[5]

^ Burke PA, DeNardo SJ, Miers LA, Lamborn KR, Matzku S, DeNardo GL (August 2002). "Cilengitide targeting of alpha(v)beta(3) integrin receptor synergizes with radioimmunotherapy to increase efficacy and apoptosis in breast cancer xenografts". Cancer Research. 62 (15): 4263–72. PMID 12154028.
^ Goodman SL, Hölzemann G, Sulyok GA, Kessler H (February 2002). "Nanomolar small molecule inhibitors for alphav(beta)6, alphav(beta)5, and alphav(beta)3 integrins". Journal of Medicinal Chemistry. 45 (5): 1045–51. doi:10.1021/jm0102598. PMID 11855984.
^ Spreitzer H (October 27, 2008). "Neue Wirkstoffe - Cilengitide". Österreichische Apothekerzeitung (in German) (22/2008): 1136–7.
^ ^a ^b Yamada S, Bu XY, Khankaldyyan V, Gonzales-Gomez I, McComb JG, Laug WE (December 2006). "Effect of the angiogenesis inhibitor Cilengitide (EMD 121974) on glioblastoma growth in nude mice". Neurosurgery. 59 (6): 1304–12, discussion 1312. doi:10.1227/01.NEU.0000245622.70344.BE. PMID 17277694. S2CID 19861713.
^ ^a ^b Mikkelsen T, Brodie C, Finniss S, Berens ME, Rennert JL, Nelson K, Lemke N, Brown SL, Hahn D, Neuteboom B, Goodman SL (June 2009). "Radiation sensitization of glioblastoma by cilengitide has unanticipated schedule-dependency". International Journal of Cancer. 124 (11): 2719–27. doi:10.1002/ijc.24240. PMID 19199360. S2CID 12073569.

[1] Burke PA, DeNardo SJ, Miers LA, Lamborn KR, Matzku S, DeNardo GL (August 2002). "Cilengitide targeting of alpha(v)beta(3) integrin receptor synergizes with radioimmunotherapy to increase efficacy and apoptosis in breast cancer xenografts". Cancer Research. 62 (15): 4263–72. PMID 12154028.

[2] Goodman SL, Hölzemann G, Sulyok GA, Kessler H (February 2002). "Nanomolar small molecule inhibitors for alphav(beta)6, alphav(beta)5, and alphav(beta)3 integrins". Journal of Medicinal Chemistry. 45 (5): 1045–51. doi:10.1021/jm0102598. PMID 11855984.

[3] Spreitzer H (October 27, 2008). "Neue Wirkstoffe - Cilengitide". Österreichische Apothekerzeitung (in German) (22/2008): 1136–7.

[Yamada2006-4] Yamada S, Bu XY, Khankaldyyan V, Gonzales-Gomez I, McComb JG, Laug WE (December 2006). "Effect of the angiogenesis inhibitor Cilengitide (EMD 121974) on glioblastoma growth in nude mice". Neurosurgery. 59 (6): 1304–12, discussion 1312. doi:10.1227/01.NEU.0000245622.70344.BE. PMID 17277694. S2CID 19861713.

[Mikkelsen2009-5] Mikkelsen T, Brodie C, Finniss S, Berens ME, Rennert JL, Nelson K, Lemke N, Brown SL, Hahn D, Neuteboom B, Goodman SL (June 2009). "Radiation sensitization of glioblastoma by cilengitide has unanticipated schedule-dependency". International Journal of Cancer. 124 (11): 2719–27. doi:10.1002/ijc.24240. PMID 19199360. S2CID 12073569.

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