Target Information

Target General Infomation
Target ID
T67103
Former ID
TTDR00473
Target Name
Integrin alpha-V
Gene Name
ITGAV
Synonyms
CD51 antigen; Vitronectin receptor alpha subunit; ITGAV
Target Type
Clinical Trial
Disease Colorectal cancer [ICD9: 153, 154; ICD10: C18-C21]
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48]
Function
The alpha-v integrins are receptors for vitronectin, cytotactin, fibronectin, fibrinogen, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin and von willebrand factor. They recognize the sequence r-g-d.
BioChemical Class
Integrin
Target Validation
T67103
UniProt ID
P06756
Sequence
MAFPPRRRLRLGPRGLPLLLSGLLLPLCRAFNLDVDSPAEYSGPEGSYFGFAVDFFVPSA
SSRMFLLVGAPKANTTQPGIVEGGQVLKCDWSSTRRCQPIEFDATGNRDYAKDDPLEFKS
HQWFGASVRSKQDKILACAPLYHWRTEMKQEREPVGTCFLQDGTKTVEYAPCRSQDIDAD
GQGFCQGGFSIDFTKADRVLLGGPGSFYWQGQLISDQVAEIVSKYDPNVYSIKYNNQLAT
RTAQAIFDDSYLGYSVAVGDFNGDGIDDFVSGVPRAARTLGMVYIYDGKNMSSLYNFTGE
QMAAYFGFSVAATDINGDDYADVFIGAPLFMDRGSDGKLQEVGQVSVSLQRASGDFQTTK
LNGFEVFARFGSAIAPLGDLDQDGFNDIAIAAPYGGEDKKGIVYIFNGRSTGLNAVPSQI
LEGQWAARSMPPSFGYSMKGATDIDKNGYPDLIVGAFGVDRAILYRARPVITVNAGLEVY
PSILNQDNKTCSLPGTALKVSCFNVRFCLKADGKGVLPRKLNFQVELLLDKLKQKGAIRR
ALFLYSRSPSHSKNMTISRGGLMQCEELIAYLRDESEFRDKLTPITIFMEYRLDYRTAAD
TTGLQPILNQFTPANISRQAHILLDCGEDNVCKPKLEVSVDSDQKKIYIGDDNPLTLIVK
AQNQGEGAYEAELIVSIPLQADFIGVVRNNEALARLSCAFKTENQTRQVVCDLGNPMKAG
TQLLAGLRFSVHQQSEMDTSVKFDLQIQSSNLFDKVSPVVSHKVDLAVLAAVEIRGVSSP
DHVFLPIPNWEHKENPETEEDVGPVVQHIYELRNNGPSSFSKAMLHLQWPYKYNNNTLLY
ILHYDIDGPMNCTSDMEINPLRIKISSLQTTEKNDTVAGQGERDHLITKRDLALSEGDIH
TLGCGVAQCLKIVCQVGRLDRGKSAILYVKSLLWTETFMNKENQNHSYSLKSSASFNVIE
FPYKNLPIEDITNSTLVTTNVTWGIQPAPMPVPVWVIILAVLAGLLLLAVLVFVMYRMGF
FKRVRPPQEEQEREQLQPHENGEGNSET
Drugs and Mode of Action
Drug(s) Abituzumab Drug Info Phase 2 Colorectal cancer [532993]
IMGN-388 Drug Info Phase 1 Solid tumours [522384]
SB-223245 Drug Info Terminated Discovery agent [546478]
Inhibitor Ac-Asp-Arg-Leu-Asp-Ser-OH Drug Info [529045]
AcDRGDS Drug Info [528659]
C(-GRGDfL-) Drug Info [529125]
C(Arg-Gly-Asp-D-Phe-Val) Drug Info [528215]
C(RGDfF) Drug Info [528059]
C(RGDfMeF) Drug Info [528059]
C(RGDfV) Drug Info [528438]
C-[-Arg-Gly-Asp-Acpca30-] Drug Info [527884]
C-[-Arg-Gly-Asp-Acpca31-] Drug Info [527884]
C-[-Arg-Gly-Asp-Acpca32-] Drug Info [527884]
C-[-Arg-Gly-Asp-Acpca33-] Drug Info [527884]
Cyclo(RGDfV) (control) Drug Info [528111]
Cyclo-[-Arg-Gly-Asp-Amp21-] Drug Info [529343]
Cyclo-[-Arg-Gly-Asp-Amp22-] Drug Info [529343]
Cyclo-[-Arg-Gly-Asp-Amp23-] Drug Info [529343]
Cyclo-[-Arg-Gly-Asp-Amp24-] Drug Info [529343]
Cyclo-[-Arg-Gly-Asp-Amp25-] Drug Info [529343]
Cyclo-[-Arg-Gly-Asp-Amp26-] Drug Info [529343]
Cyclo-[-Arg-Gly-Asp-Amp27-] Drug Info [529343]
Cyclo-[-Arg-Gly-Asp-Amp28-] Drug Info [529343]
CYCLORGDFV Drug Info [530622]
Cyclo[RGDfK(cypate)] Drug Info [528111]
Cypate-[(RGD)2-NH2]1 Drug Info [528111]
Cypate-[(RGD)2-NH2]2 Drug Info [528111]
Cypate-[(RGD)3-NH2]1 Drug Info [528111]
Cypate-[(RGD)3-NH2]2 Drug Info [528111]
Cypate-[(RGD)4-NH2]1 Drug Info [528111]
Cypate-[(RGD)4-NH2]2 Drug Info [528111]
C[-Arg-Gly-Asp-Acpca19-] Drug Info [527884]
C[-Arg-Gly-Asp-Acpca20-] Drug Info [527884]
C[-Arg-Gly-Asp-Acpca21-] Drug Info [527884]
C[-Arg-Gly-Asp-Acpca22-] Drug Info [527884]
C[-Arg-Gly-Asp-Acpca34-] Drug Info [527884]
C[-Arg-Gly-Asp-Acpca35-] Drug Info [527884]
C[-Arg-Gly-Asp-Acpca36-] Drug Info [527884]
C[RGD-(R)-alpha-TfmfV] Drug Info [528059]
C[RGD-(S)-alpha-TfmfV] Drug Info [528059]
C[RGDf-(3R)-Carboxymorpholine] Drug Info [529951]
C[RGDf-(3S)-Carboxymorpholine] Drug Info [529951]
C[RGDf-(R)-alpha-TfmF] Drug Info [528059]
C[RGDf-(R)-alpha-TfmV] Drug Info [528059]
C[RGDf-(R)-N-Me-alpha-TfmF] Drug Info [528059]
C[RGDf-(S)-alpha-TfmF] Drug Info [528059]
C[RGDf-(S)-alpha-TfmV] Drug Info [528059]
C[RGDf-(S)-N-Me-alpha-TfmF] Drug Info [528059]
C[RGDf-(S,R)-alpha-Dfm-F] Drug Info [528059]
E[c(RGDyK)]2 Drug Info [527440]
E[c(RGDyK)]2-PTX conjugate Drug Info [527440]
G(D-Pen)-G-H-R-G-D-L-R-C-A Drug Info [533606]
Gly-Arg-Gly-Asp-Ser Drug Info [530479]
Gly-Arg-Gly-Asp-Ser-Pro-Lys Drug Info [525558]
ISONIPECOTAMIDE Drug Info [527223]
N-(3,5-dichlorophenyl)imidodicarbonimidic diamide Drug Info [530779]
NAVPNLRGDLQVLAQKVART Drug Info [528633]
RGDechi Drug Info [528215]
SB-223245 Drug Info [534805]
SB-265123 Drug Info [527268]
ST-1646 Drug Info [529343]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Phagosome
PI3K-Akt signaling pathway
Focal adhesion
ECM-receptor interaction
Cell adhesion molecules (CAMs)
Regulation of actin cytoskeleton
Thyroid hormone signaling pathway
Pathways in cancer
Proteoglycans in cancer
Small cell lung cancer
Hypertrophic cardiomyopathy (HCM)
Arrhythmogenic right ventricular cardiomyopathy (ARVC)
Dilated cardiomyopathy
PANTHER Pathway Integrin signalling pathway
CCKR signaling map ST
Pathway Interaction Database Beta1 integrin cell surface interactions
Integrin family cell surface interactions
Beta3 integrin cell surface interactions
S1P3 pathway
Osteopontin-mediated events
Arf6 trafficking events
Nectin adhesion pathway
S1P1 pathway
CXCR4-mediated signaling events
Plexin-D1 Signaling
Integrins in angiogenesis
Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling
PDGFR-beta signaling pathway
PDGFR-alpha signaling pathway
Beta5 beta6 beta7 and beta8 integrin cell surface interactions
Signaling events mediated by VEGFR1 and VEGFR2
Signaling events mediated by focal adhesion kinase
Reactome Cross-presentation of particulate exogenous antigens (phagosomes)
Elastic fibre formation
PECAM1 interactions
Molecules associated with elastic fibres
Integrin cell surface interactions
Laminin interactions
Syndecan interactions
ECM proteoglycans
VEGFA-VEGFR2 Pathway
WikiPathways Osteoblast Signaling
Focal Adhesion
Class I MHC mediated antigen processing &amp
presentation
Syndecan interactions
Extracellular matrix organization
Elastic fibre formation
Primary Focal Segmental Glomerulosclerosis FSGS
Arrhythmogenic Right Ventricular Cardiomyopathy
Integrin-mediated Cell Adhesion
L1CAM interactions
Integrin cell surface interactions
Cell surface interactions at the vascular wall
Osteopontin Signaling
References
Ref 522384ClinicalTrials.gov (NCT00721669) A Phase I Dose-Escalation Study of IMGN388 in Patients With Solid Tumors. U.S. National Institutes of Health.
Ref 532993Abituzumab combined with cetuximab plus irinotecan versus cetuximab plus irinotecan alone for patients with KRAS wild-type metastatic colorectal cancer: the randomised phase I/II POSEIDON trial. Ann Oncol. 2015 Jan;26(1):132-40.
Ref 546478Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008429)
Ref 525558J Med Chem. 1999 Aug 12;42(16):3033-40.N-Methylated cyclic RGD peptides as highly active and selective alpha(V)beta(3) integrin antagonists.
Ref 527223Bioorg Med Chem Lett. 2004 Oct 18;14(20):5227-32.Piperidine-containing beta-arylpropionic acids as potent antagonists of alphavbeta3/alphavbeta5 integrins.
Ref 527268Bioorg Med Chem Lett. 2004 Dec 6;14(23):5937-41.1,2,3,4-Tetrahydroquinoline-containing alphaVbeta3 integrin antagonists with enhanced oral bioavailability.
Ref 527440J Med Chem. 2005 Feb 24;48(4):1098-106.Synthesis and biological evaluation of dimeric RGD peptide-paclitaxel conjugate as a model for integrin-targeted drug delivery.
Ref 527884J Med Chem. 2005 Dec 1;48(24):7675-87.Grafting aminocyclopentane carboxylic acids onto the RGD tripeptide sequence generates low nanomolar alphaVbeta3/alphaVbeta5 integrin dual binders.
Ref 528059J Med Chem. 2006 Mar 9;49(5):1808-17.Incorporation of the unusual C(alpha)-fluoroalkylamino acids into cyclopeptides: synthesis of arginine-glycine-aspartate (RGD) analogues and study of their conformational and biological behavior.
Ref 528111J Med Chem. 2006 Apr 6;49(7):2268-75.Design, synthesis, and evaluation of near infrared fluorescent multimeric RGD peptides for targeting tumors.
Ref 528215J Med Chem. 2006 Jun 1;49(11):3416-20.Novel and selective alpha(v)beta3 receptor peptide antagonist: design, synthesis, and biological behavior.
Ref 528438Bioorg Med Chem Lett. 2006 Nov 15;16(22):5878-82. Epub 2006 Sep 18.Discovery of small molecule inhibitors of integrin alphavbeta3 through structure-based virtual screening.
Ref 528633J Biol Chem. 2007 Mar 30;282(13):9657-65. Epub 2007 Jan 23.Structure-function analysis of Arg-Gly-Asp helix motifs in alpha v beta 6 integrin ligands.
Ref 528659Bioorg Med Chem Lett. 2007 Apr 15;17(8):2329-33. Epub 2007 Jan 27.Inhibition of cancer cell adhesion by heterochiral Pro-containing RGD mimetics.
Ref 529045Bioorg Med Chem. 2007 Dec 1;15(23):7380-90. Epub 2007 Aug 22.Synthesis and biological evaluation of non-peptide alpha(v)beta(3)/alpha(5)beta(1) integrin dual antagonists containing 5,6-dihydropyridin-2-one scaffolds.
Ref 529125J Med Chem. 2007 Nov 29;50(24):5878-81. Epub 2007 Nov 1.Multiple N-methylation by a designed approach enhances receptor selectivity.
Ref 529343J Med Chem. 2008 Mar 27;51(6):1771-82. Epub 2008 Feb 28.Discovery of subnanomolar arginine-glycine-aspartate-based alphaVbeta3/alphaVbeta5 integrin binders embedding 4-aminoproline residues.
Ref 529951Bioorg Med Chem. 2009 Feb 15;17(4):1542-9. Epub 2009 Jan 13.Morpholine-based RGD-cyclopentapeptides as alphavbeta3/alphavbeta5 integrin ligands: role of configuration towards receptor binding affinity.
Ref 530479J Med Chem. 2009 Nov 26;52(22):7029-43.alphavbeta3 Integrin-targeting Arg-Gly-Asp (RGD) peptidomimetics containing oligoethylene glycol (OEG) spacers.
Ref 530622J Med Chem. 2010 Jan 14;53(1):106-18.Antiangiogenic effect of dual/selective alpha(5)beta(1)/alpha(v)beta(3) integrin antagonists designed on partially modified retro-inverso cyclotetrapeptide mimetics.
Ref 530779J Med Chem. 2010 Jun 10;53(11):4332-53.Emerging targets in osteoporosis disease modification.
Ref 531160Anti-alphav integrin monoclonal antibody intetumumab enhances the efficacy of radiation therapy and reduces metastasis of human cancer xenografts in nude rats. Cancer Res. 2010 Oct 1;70(19):7591-9.
Ref 532993Abituzumab combined with cetuximab plus irinotecan versus cetuximab plus irinotecan alone for patients with KRAS wild-type metastatic colorectal cancer: the randomised phase I/II POSEIDON trial. Ann Oncol. 2015 Jan;26(1):132-40.
Ref 533606J Med Chem. 1994 Jan 7;37(1):1-8.Design and synthesis of novel cyclic RGD-containing peptides as highly potent and selective integrin alpha IIb beta 3 antagonists.
Ref 534805Bioorg Med Chem Lett. 1998 Nov 17;8(22):3171-6.Discovery of an imidazopyridine-containing 1,4-benzodiazepine nonpeptide vitronectin receptor (alpha v beta 3) antagonist with efficacy in a restenosis model.

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