Target Information
| Target General Information | Top | |||||
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| Target ID |
T67363
(Former ID: TTDI01789)
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| Target Name |
Integrin alpha-V/beta-3 (ITGAV/B3)
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| Synonyms |
Integrin alphaVbeta3; Integrin alpha-v beta-3; Integrin alpha V beta 3; Alpha(v)beta(3) Integrin; Alpha v beta 3 integrin
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| Gene Name |
ITGAV-ITGB3
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Rheumatoid arthritis [ICD-11: FA20] | |||||
| Function |
Receptor for phagocytosis on macrophages or dendritic cells. In cancer and other diseases, its role in angiogenesis is directly responsible to providing blood supply to problematic overgrowths.
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| BioChemical Class |
Integrin
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| UniProt ID | ||||||
| Sequence |
MRARPRPRPLWATVLALGALAGVGVGGPNICTTRGVSSCQQCLAVSPMCAWCSDEALPLG
SPRCDLKENLLKDNCAPESIEFPVSEARVLEDRPLSDKGSGDSSQVTQVSPQRIALRLRP DDSKNFSIQVRQVEDYPVDIYYLMDLSYSMKDDLWSIQNLGTKLATQMRKLTSNLRIGFG AFVDKPVSPYMYISPPEALENPCYDMKTTCLPMFGYKHVLTLTDQVTRFNEEVKKQSVSR NRDAPEGGFDAIMQATVCDEKIGWRNDASHLLVFTTDAKTHIALDGRLAGIVQPNDGQCH VGSDNHYSASTTMDYPSLGLMTEKLSQKNINLIFAVTENVVNLYQNYSELIPGTTVGVLS MDSSNVLQLIVDAYGKIRSKVELEVRDLPEELSLSFNATCLNNEVIPGLKSCMGLKIGDT VSFSIEAKVRGCPQEKEKSFTIKPVGFKDSLIVQVTFDCDCACQAQAEPNSHRCNNGNGT FECGVCRCGPGWLGSQCECSEEDYRPSQQDECSPREGQPVCSQRGECLCGQCVCHSSDFG KITGKYCECDDFSCVRYKGEMCSGHGQCSCGDCLCDSDWTGYYCNCTTRTDTCMSSNGLL CSGRGKCECGSCVCIQPGSYGDTCEKCPTCPDACTFKKECVECKKFDRGALHDENTCNRY CRDEIESVKELKDTGKDAVNCTYKNEDDCVVRFQYYEDSSGKSILYVVEEPECPKGPDIL VVLLSVMGAILLIGLAALLIWKLLITIHDRKEFAKFEEERARAKWDTANNPLYKEATSTF TNITYRGTMAFPPRRRLRLGPRGLPLLLSGLLLPLCRAFNLDVDSPAEYSGPEGSYFGFA VDFFVPSASSRMFLLVGAPKANTTQPGIVEGGQVLKCDWSSTRRCQPIEFDATGNRDYAK DDPLEFKSHQWFGASVRSKQDKILACAPLYHWRTEMKQEREPVGTCFLQDGTKTVEYAPC RSQDIDADGQGFCQGGFSIDFTKADRVLLGGPGSFYWQGQLISDQVAEIVSKYDPNVYSI KYNNQLATRTAQAIFDDSYLGYSVAVGDFNGDGIDDFVSGVPRAARTLGMVYIYDGKNMS SLYNFTGEQMAAYFGFSVAATDINGDDYADVFIGAPLFMDRGSDGKLQEVGQVSVSLQRA SGDFQTTKLNGFEVFARFGSAIAPLGDLDQDGFNDIAIAAPYGGEDKKGIVYIFNGRSTG LNAVPSQILEGQWAARSMPPSFGYSMKGATDIDKNGYPDLIVGAFGVDRAILYRARPVIT VNAGLEVYPSILNQDNKTCSLPGTALKVSCFNVRFCLKADGKGVLPRKLNFQVELLLDKL KQKGAIRRALFLYSRSPSHSKNMTISRGGLMQCEELIAYLRDESEFRDKLTPITIFMEYR LDYRTAADTTGLQPILNQFTPANISRQAHILLDCGEDNVCKPKLEVSVDSDQKKIYIGDD NPLTLIVKAQNQGEGAYEAELIVSIPLQADFIGVVRNNEALARLSCAFKTENQTRQVVCD LGNPMKAGTQLLAGLRFSVHQQSEMDTSVKFDLQIQSSNLFDKVSPVVSHKVDLAVLAAV EIRGVSSPDHVFLPIPNWEHKENPETEEDVGPVVQHIYELRNNGPSSFSKAMLHLQWPYK YNNNTLLYILHYDIDGPMNCTSDMEINPLRIKISSLQTTEKNDTVAGQGERDHLITKRDL ALSEGDIHTLGCGVAQCLKIVCQVGRLDRGKSAILYVKSLLWTETFMNKENQNHSYSLKS SASFNVIEFPYKNLPIEDITNSTLVTTNVTWGIQPAPMPVPVWVIILAVLAGLLLLAVLV FVMYRMGFFKRVRPPQEEQEREQLQPHENGEGNSET Click to Show/Hide
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| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 7 Clinical Trial Drugs | + | ||||
| 1 | Cilengitide | Drug Info | Phase 3 | Rheumatoid arthritis | [2], [3] | |
| 2 | ATN-161 | Drug Info | Phase 2 | Renal cell carcinoma | [4] | |
| 3 | Fluciclatide F-18 | Drug Info | Phase 2 | Solid tumour/cancer | [5] | |
| 4 | Intetumumab | Drug Info | Phase 2 | Prostate cancer | [6] | |
| 5 | VLTS-589 | Drug Info | Phase 2 | Peripheral vascular disease | [7] | |
| 6 | SF0166 | Drug Info | Phase 1/2 | Diabetic macular edema | [8] | |
| 7 | AMEP | Drug Info | Phase 1 | Melanoma | [9] | |
| Discontinued Drug(s) | [+] 4 Discontinued Drugs | + | ||||
| 1 | Vitaxin | Drug Info | Discontinued in Phase 2 | Solid tumour/cancer | [10] | |
| 2 | SB-267268 | Drug Info | Discontinued in Phase 1 | Osteoporosis | [11] | |
| 3 | SB-273005 | Drug Info | Discontinued in Phase 1 | Osteoporosis | [12] | |
| 4 | PS-388023 | Drug Info | Terminated | Ocular disease | [13] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Modulator | [+] 10 Modulator drugs | + | ||||
| 1 | Cilengitide | Drug Info | [14], [15] | |||
| 2 | Fluciclatide F-18 | Drug Info | [16] | |||
| 3 | Intetumumab | Drug Info | [17] | |||
| 4 | VLTS-589 | Drug Info | [18] | |||
| 5 | AMEP | Drug Info | [19] | |||
| 6 | Vitaxin | Drug Info | [20], [21] | |||
| 7 | SB-267268 | Drug Info | [22] | |||
| 8 | SB-273005 | Drug Info | [23] | |||
| 9 | PS-388023 | Drug Info | [13] | |||
| 10 | 18F-SMIBR-K5 | Drug Info | [24] | |||
| Antagonist | [+] 3 Antagonist drugs | + | ||||
| 1 | ATN-161 | Drug Info | [1] | |||
| 2 | SF0166 | Drug Info | [8] | |||
| 3 | IS20I | Drug Info | [25] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
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| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| References | Top | |||||
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| REF 1 | 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. | |||||
| REF 2 | 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). | |||||
| REF 3 | 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. | |||||
| REF 4 | ClinicalTrials.gov (NCT00131651) ATN-161 in Advanced Renal Cell Cancer. U.S. National Institutes of Health. | |||||
| REF 5 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800032798) | |||||
| REF 6 | ClinicalTrials.gov (NCT00537381) An Efficacy and Safety Study of Intetumumab (CNTO 95) in Participants With Metastatic Hormone Refractory Prostate Cancer. U.S. National Institutes of Health. | |||||
| REF 7 | ClinicalTrials.gov (NCT00068133) Trial of VLTS-589 in Subjects With Intermittent Claudication. U.S. National Institutes of Health. | |||||
| REF 8 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 9 | Pre-EMP-tive strike against GBM. SciBX 7(14); doi:10.1038/scibx.2014.389. April 10 2014 | |||||
| REF 10 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004890) | |||||
| REF 11 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800013716) | |||||
| REF 12 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800013133) | |||||
| REF 13 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022665) | |||||
| REF 14 | 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. | |||||
| REF 15 | Pharmacological inhibition of integrin alphavbeta3 aggravates experimental liver fibrosis and suppresses hepatic angiogenesis.Hepatology.2009 Nov;50(5):1501-11. | |||||
| REF 16 | 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. | |||||
| REF 17 | 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. | |||||
| REF 18 | AbbVie Licenses Phase II-Ready Antibody Programme to Receptos for Development in Eosinophilic Oesophagitis. 2013(4), Page 35. | |||||
| REF 19 | 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. | |||||
| REF 20 | 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. | |||||
| REF 21 | Validation and comparison of anti-v3 and anti-v5 rabbit monoclonal versus murine monoclonal antibodies in four different tumor entities.Appl Immunohistochem Mol Morphol.2013 Dec;21(6):553-60. | |||||
| REF 22 | 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. | |||||
| REF 23 | 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. | |||||
| REF 24 | Synthesis of [18F]RGD-K5 by catalyzed [3 + 2] cycloaddition for imaging integrin alphavbeta3 expression in vivo. Nucl Med Biol. 2013 Jul;40(5):710-6. | |||||
| REF 25 | IS20I, a specific alphavbeta3 integrin inhibitor, reduces glioma growth in vivo. Neurosurgery. 2003 Jan;52(1):177-85; discussion 185-6. | |||||
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