Details of the Drug

General Information of Drug (ID: DMEAOZ0)

Drug Name
Cilengitide
Synonyms
Cilengitide; 188968-51-6; EMD-121974; Cilengitide [USAN:INN]; UNII-4EDF46E4GI; EMD121974; EMD-12192; EMD 121974; 4EDF46E4GI; CHEMBL429876; 2-[(2S,5R,8S,11S)-5-benzyl-11-[3-(diaminomethylideneamino)propyl]-7-methyl-3,6,9,12,15-pentaoxo-8-propan-2-yl-1,4,7,10,13-pentazacyclopentadec-2-yl]acetic acid; Cyclo(L-arginylglycyl-L-aspartyl-D-phenylalanyl-N-methyl-L-valyl); Cyclo(L-arginylglycyl-L-alpha-aspartyl-D-phenylalanyl-N-methyl-L-valyl); Cilengitide (TFA salt)
Indication
Disease Entry ICD 11 Status REF
Rheumatoid arthritis FA20 Phase 3 [1], [2]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 2 Molecular Weight (mw) 588.7
Topological Polar Surface Area (xlogp) -1
Rotatable Bond Count (rotbonds) 9
Hydrogen Bond Donor Count (hbonddonor) 7
Hydrogen Bond Acceptor Count (hbondacc) 8
Chemical Identifiers
Formula
C27H40N8O7
IUPAC Name
2-[(2S,5R,8S,11S)-5-benzyl-11-[3-(diaminomethylideneamino)propyl]-7-methyl-3,6,9,12,15-pentaoxo-8-propan-2-yl-1,4,7,10,13-pentazacyclopentadec-2-yl]acetic acid
Canonical SMILES
CC(C)[C@H]1C(=O)N[C@H](C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](C(=O)N1C)CC2=CC=CC=C2)CC(=O)O)CCCN=C(N)N
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
InChIKey
AMLYAMJWYAIXIA-VWNVYAMZSA-N
Cross-matching ID
PubChem CID
176873
CAS Number
188968-51-6
DrugBank ID
DB11890
TTD ID
D09ZXO

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Integrin alpha-V/beta-3 (ITGAV/B3) TT69TQN ITAV_HUMAN-ITB3_HUMAN Modulator [3], [4]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Rheumatoid arthritis
ICD Disease Classification FA20
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Integrin alpha-V/beta-3 (ITGAV/B3) DTT ITGAV-ITGB3 8.19E-02 -0.16 -0.46
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6597).
2 ClinicalTrials.gov (NCT00689221) Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Methylated Gene Promoter Status. U.S. National Institutes of Health.
3 The integrin antagonist cilengitide activates alphaVbeta3, disrupts VE-cadherin localization at cell junctions and enhances permeability in endothelial cells.PLoS One.2009;4(2):e4449.
4 Pharmacological inhibition of integrin alphavbeta3 aggravates experimental liver fibrosis and suppresses hepatic angiogenesis.Hepatology.2009 Nov;50(5):1501-11.
5 A non-RGD-based integrin binding peptide (ATN-161) blocks breast cancer growth and metastasis in vivo. Mol Cancer Ther. 2006 Sep;5(9):2271-80.
6 A randomised, phase II study of intetumumab, an anti-alphav-integrin mAb, alone and with dacarbazine in stage IV melanoma. Br J Cancer. 2011 Jul 26;105(3):346-52.
7 AbbVie Licenses Phase II-Ready Antibody Programme to Receptos for Development in Eosinophilic Oesophagitis. 2013(4), Page 35.
8 Use of a novel Arg-Gly-Asp radioligand, 18F-AH111585, to determine changes in tumor vascularity after antitumor therapy.J Nucl Med.2009 Jan;50(1):116-22.
9 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
10 Gene electrotransfer of plasmid AMEP, an integrin-targeted therapy, has antitumor and antiangiogenic action in murine B16 melanoma.Gene Ther.2015 Jul;22(7):578-90.
11 Monoclonal antibodies to alphaVbeta3 (7E3 and LM609) inhibit sickle red blood cell-endothelium interactions induced by platelet-activating factor. Blood. 2000 Jan 15;95(2):368-74.
12 SB-267268, a nonpeptidic antagonist of alpha(v)beta3 and alpha(v)beta5 integrins, reduces angiogenesis and VEGF expression in a mouse model of retinopathy of prematurity. Invest Ophthalmol Vis Sci. 2006 Apr;47(4):1600-5.
13 Disease-modifying activity of SB 273005, an orally active, nonpeptide alphavbeta3 (vitronectin receptor) antagonist, in rat adjuvant-induced arthri... Arthritis Rheum. 2001 Jan;44(1):128-37.
14 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.