Details of the Drug

General Information of Drug (ID: DMIBFAV)

Drug Name
SB-267268
Synonyms 2-[3-Oxo-8-[3-(2-pyridylamino)propoxy]-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydro-1H-2-benzazepin-4(S)-yl]acetic acid
Indication
Disease Entry ICD 11 Status REF
Osteoporosis FB83.0 Discontinued in Phase 1 [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 451.4
Topological Polar Surface Area (xlogp) 3.1
Rotatable Bond Count (rotbonds) 9
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 9
Chemical Identifiers
Formula
C22H24F3N3O4
IUPAC Name
2-[(4S)-3-oxo-8-[3-(pyridin-2-ylamino)propoxy]-2-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-2-benzazepin-4-yl]acetic acid
Canonical SMILES
C1[C@H](C(=O)N(CC2=C1C=CC(=C2)OCCCNC3=CC=CC=N3)CC(F)(F)F)CC(=O)O
InChI
InChI=1S/C22H24F3N3O4/c23-22(24,25)14-28-13-17-11-18(32-9-3-8-27-19-4-1-2-7-26-19)6-5-15(17)10-16(21(28)31)12-20(29)30/h1-2,4-7,11,16H,3,8-10,12-14H2,(H,26,27)(H,29,30)/t16-/m0/s1
InChIKey
PVDGZHKJXXVONO-INIZCTEOSA-N
Cross-matching ID
PubChem CID
9955461
TTD ID
D02VIP

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 [2]
Integrin alpha-V/beta-5 (ITGAV/B5) TTPRDH7 ITAV_HUMAN-ITB5_HUMAN Modulator [2]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Osteoporosis
ICD Disease Classification FB83.0
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Integrin alpha-V/beta-5 (ITGAV/B5) DTT ITGAV-ITGB5 2.88E-04 2.42 1.71
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 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800013716)
2 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.
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 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.
5 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.
6 AbbVie Licenses Phase II-Ready Antibody Programme to Receptos for Development in Eosinophilic Oesophagitis. 2013(4), Page 35.
7 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.
8 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
9 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.
10 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.
11 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.
12 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.