Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTJA1ZO)

• DTT Name: ITGB3 messenger RNA (ITGB3 mRNA)
• Synonyms: Platelet membrane glycoprotein IIIa (mRNA); Integrin beta-3 (mRNA); GPIIIa (mRNA); GP3A (mRNA); CD61 (mRNA)
• Gene Name: ITGB3
• DTT Type: Discontinued target; [1]
• BioChemical Class: mRNA target
• UniProt ID: ITB3_HUMAN
• TTD ID: T23355
• Sequence:
  MRARPRPRPLWATVLALGALAGVGVGGPNICTTRGVSSCQQCLAVSPMCAWCSDEALPLG
  SPRCDLKENLLKDNCAPESIEFPVSEARVLEDRPLSDKGSGDSSQVTQVSPQRIALRLRP
  DDSKNFSIQVRQVEDYPVDIYYLMDLSYSMKDDLWSIQNLGTKLATQMRKLTSNLRIGFG
  AFVDKPVSPYMYISPPEALENPCYDMKTTCLPMFGYKHVLTLTDQVTRFNEEVKKQSVSR
  NRDAPEGGFDAIMQATVCDEKIGWRNDASHLLVFTTDAKTHIALDGRLAGIVQPNDGQCH
  VGSDNHYSASTTMDYPSLGLMTEKLSQKNINLIFAVTENVVNLYQNYSELIPGTTVGVLS
  MDSSNVLQLIVDAYGKIRSKVELEVRDLPEELSLSFNATCLNNEVIPGLKSCMGLKIGDT
  VSFSIEAKVRGCPQEKEKSFTIKPVGFKDSLIVQVTFDCDCACQAQAEPNSHRCNNGNGT
  FECGVCRCGPGWLGSQCECSEEDYRPSQQDECSPREGQPVCSQRGECLCGQCVCHSSDFG
  KITGKYCECDDFSCVRYKGEMCSGHGQCSCGDCLCDSDWTGYYCNCTTRTDTCMSSNGLL
  CSGRGKCECGSCVCIQPGSYGDTCEKCPTCPDACTFKKECVECKKFDRGALHDENTCNRY
  CRDEIESVKELKDTGKDAVNCTYKNEDDCVVRFQYYEDSSGKSILYVVEEPECPKGPDIL
  VVLLSVMGAILLIGLAALLIWKLLITIHDRKEFAKFEEERARAKWDTANNPLYKEATSTF
  TNITYRGT
• Function: Integrin alpha-IIb/beta-3 (ITGA2B:ITGB3) is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. Integrins alpha-IIb/beta-3 and alpha-V/beta-3 recognize the sequence R-G-D in a wide array of ligands. Integrin alpha-IIb/beta-3 recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha-IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial surface. Fibrinogen binding enhances SELP expression in activated platelets. ITGAV:ITGB3 binds to fractalkine (CX3CL1) and acts as its coreceptor in CX3CR1-dependent fractalkine signaling. ITGAV:ITGB3 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling. ITGAV:ITGB3 binds to FGF1 and this binding is essential for FGF1 signaling. ITGAV:ITGB3 binds to FGF2 and this binding is essential for FGF2 signaling. ITGAV:ITGB3 binds to IGF1 and this binding is essential for IGF1 signaling. ITGAV:ITGB3 binds to IGF2 and this binding is essential for IGF2 signaling. ITGAV:ITGB3 binds to IL1B and this binding is essential for IL1B signaling. ITGAV:ITGB3 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1. ITGAV:ITGB3 acts as a receptor for fibrillin-1 (FBN1) and mediates R-G-D-dependent cell adhesion to FBN1. Integrin alpha-V/beta-3 (ITGAV:ITGB3) is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Willebrand factor.
• KEGG Pathway:
  Rap1 signaling pathway (hsa04015)
  Phagosome (hsa04145)
  PI3K-Akt signaling pathway (hsa04151)
  Osteoclast differentiation (hsa04380)
  Focal adhesion (hsa04510)
  ECM-receptor interaction (hsa04512)
  Platelet activation (hsa04611)
  Hematopoietic cell lineage (hsa04640)
  Regulation of actin cytoskeleton (hsa04810)
  Thyroid hormone signaling pathway (hsa04919)
  Proteoglycans in cancer (hsa05205)
  MicroRNAs in cancer (hsa05206)
  Hypertrophic cardiomyopathy (HCM) (hsa05410)
  Arrhythmogenic right ventricular cardiomyopathy (ARVC) (hsa05412)
  Dilated cardiomyopathy (hsa05414)
• Reactome Pathway:
  Elastic fibre formation (R-HSA-1566948)
  PECAM1 interactions (R-HSA-210990)
  Molecules associated with elastic fibres (R-HSA-2129379)
  Integrin cell surface interactions (R-HSA-216083)
  Syndecan interactions (R-HSA-3000170)
  ECM proteoglycans (R-HSA-3000178)
  Integrin alphaIIb beta3 signaling (R-HSA-354192)
  GRB2 (R-HSA-354194)
  p130Cas linkage to MAPK signaling for integrins (R-HSA-372708)
  VEGFA-VEGFR2 Pathway (R-HSA-4420097)
  MAP2K and MAPK activation (R-HSA-5674135)
  Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DTT

10 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
XEMILOFIBAN	DMBRYT8	Cardiovascular disease	BA00-BE2Z	Discontinued in Phase 3	[1]
DMP-802	DMDK6HP	N. A.	N. A.	Discontinued in Phase 1	[2]
DMP-757	DMGNUXC	N. A.	N. A.	Terminated	[3]
L-709780	DMB3ZTI	N. A.	N. A.	Terminated	[4]
L-738167	DMO69X8	N. A.	N. A.	Terminated	[2]
Ro-43-5054	DMPNHF0	N. A.	N. A.	Terminated	[2]
Ro-43-8857	DM4VY8S	N. A.	N. A.	Terminated	[2]
SB-223245	DM3JQCF	N. A.	N. A.	Terminated	[5]
SC-47643	DMIE039	N. A.	N. A.	Terminated	[6]
SKF-107260	DMM8F0V	N. A.	N. A.	Terminated	[7]

67 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
3-(3-(benzamido)-5-nitrobenzamido)propanoic acid	DMY4VX2	Discovery agent	N.A.	Investigative	[8]
3-(3-(carbamoyl)benzamido)-3-phenylpropanoic acid	DM2K51S	Discovery agent	N.A.	Investigative	[8]
3-(3-(carbamoyl)benzamido)propanoic acid	DM31JAZ	Discovery agent	N.A.	Investigative	[8]
Ac-Asp-Arg-Leu-Asp-Ser-OH	DMYHADT	Discovery agent	N.A.	Investigative	[9]
AcDRGDS	DM9MDBO	Discovery agent	N.A.	Investigative	[10]
C(-GRGDfL-)	DMTMJAI	Discovery agent	N.A.	Investigative	[11]
C(Arg-Gly-Asp-D-Phe-Val)	DMHNZGP	Discovery agent	N.A.	Investigative	[12]
C(RGDfF)	DMMBESU	Discovery agent	N.A.	Investigative	[13]
C(RGDfMeF)	DM8DU42	Discovery agent	N.A.	Investigative	[13]
C-[-Arg-Gly-Asp-Acpca30-]	DML0U8B	Discovery agent	N.A.	Investigative	[14]
C-[-Arg-Gly-Asp-Acpca31-]	DMKENFU	Discovery agent	N.A.	Investigative	[14]
C-[-Arg-Gly-Asp-Acpca32-]	DMVM7B2	Discovery agent	N.A.	Investigative	[14]
C-[-Arg-Gly-Asp-Acpca33-]	DMIBGWO	Discovery agent	N.A.	Investigative	[14]
Cyclo(RGDfV) (control)	DM3QVOB	Discovery agent	N.A.	Investigative	[15]
Cyclo-[-Arg-Gly-Asp-Amp21-]	DMVXPUB	Discovery agent	N.A.	Investigative	[16]
Cyclo-[-Arg-Gly-Asp-Amp22-]	DMBELJK	Discovery agent	N.A.	Investigative	[16]
Cyclo-[-Arg-Gly-Asp-Amp23-]	DMT29VJ	Discovery agent	N.A.	Investigative	[16]
Cyclo-[-Arg-Gly-Asp-Amp24-]	DM35ZLK	Discovery agent	N.A.	Investigative	[16]
Cyclo-[-Arg-Gly-Asp-Amp25-]	DMEIXUQ	Discovery agent	N.A.	Investigative	[16]
Cyclo-[-Arg-Gly-Asp-Amp26-]	DME5HRW	Discovery agent	N.A.	Investigative	[16]
Cyclo-[-Arg-Gly-Asp-Amp27-]	DMBNJZ0	Discovery agent	N.A.	Investigative	[16]
Cyclo-[-Arg-Gly-Asp-Amp28-]	DMJMHAV	Discovery agent	N.A.	Investigative	[16]
CYCLORGDFV	DMGZ0KM	N. A.	N. A.	Investigative	[17]
Cyclo[RGDfK(cypate)]	DMWYFLD	Discovery agent	N.A.	Investigative	[15]
Cypate-[(RGD)2-NH2]1	DMBTU7G	Discovery agent	N.A.	Investigative	[15]
Cypate-[(RGD)2-NH2]2	DMJNW9P	Discovery agent	N.A.	Investigative	[15]
Cypate-[(RGD)3-NH2]1	DMWINK5	Discovery agent	N.A.	Investigative	[15]
Cypate-[(RGD)3-NH2]2	DM1SAIX	Discovery agent	N.A.	Investigative	[15]
Cypate-[(RGD)4-NH2]1	DM3GLMP	Discovery agent	N.A.	Investigative	[15]
Cypate-[(RGD)4-NH2]2	DMR74OM	Discovery agent	N.A.	Investigative	[15]
C[-Arg-Gly-Asp-Acpca19-]	DMPOIDK	Discovery agent	N.A.	Investigative	[14]
C[-Arg-Gly-Asp-Acpca20-]	DMJVW1N	Discovery agent	N.A.	Investigative	[14]
C[-Arg-Gly-Asp-Acpca21-]	DMXCUDV	Discovery agent	N.A.	Investigative	[14]
C[-Arg-Gly-Asp-Acpca22-]	DM6DV90	Discovery agent	N.A.	Investigative	[14]
C[-Arg-Gly-Asp-Acpca34-]	DMKHSAV	Discovery agent	N.A.	Investigative	[14]
C[-Arg-Gly-Asp-Acpca35-]	DMQOY3J	Discovery agent	N.A.	Investigative	[14]
C[-Arg-Gly-Asp-Acpca36-]	DM7LCPW	Discovery agent	N.A.	Investigative	[14]
C[RGD-(R)-alpha-TfmfV]	DMF091Y	Discovery agent	N.A.	Investigative	[13]
C[RGD-(S)-alpha-TfmfV]	DMC9G2Y	Discovery agent	N.A.	Investigative	[13]
C[RGDf-(R)-alpha-TfmF]	DMXA0JB	Discovery agent	N.A.	Investigative	[13]
C[RGDf-(R)-alpha-TfmV]	DM8FGMA	Discovery agent	N.A.	Investigative	[13]
C[RGDf-(R)-N-Me-alpha-TfmF]	DM4ZWOD	Discovery agent	N.A.	Investigative	[13]
C[RGDf-(S)-alpha-TfmF]	DMCXJOL	Discovery agent	N.A.	Investigative	[13]
C[RGDf-(S)-alpha-TfmV]	DMLRYXK	Discovery agent	N.A.	Investigative	[13]
C[RGDf-(S)-N-Me-alpha-TfmF]	DMNS3HC	Discovery agent	N.A.	Investigative	[13]
C[RGDf-(S,R)-alpha-Dfm-F]	DMAILK8	Discovery agent	N.A.	Investigative	[13]
E[c(RGDyK)]2	DM76UJY	Discovery agent	N.A.	Investigative	[18]
E[c(RGDyK)]2-PTX conjugate	DMS1LZI	Discovery agent	N.A.	Investigative	[18]
Gly-Arg-Gly-Asp-Ser	DMACT8D	Discovery agent	N.A.	Investigative	[19]
Gly-Arg-Gly-Asp-Ser-Pro-Lys	DMGOIME	Discovery agent	N.A.	Investigative	[20]
ISIS 196103	DM1NJD7	Discovery agent	N.A.	Investigative	[21]
ISIS 25237	DMD75MP	Discovery agent	N.A.	Investigative	[21]
ISONIPECOTAMIDE	DM5DKUY	Discovery agent	N.A.	Investigative	[22]
L-734115	DMDNVTF	Discovery agent	N.A.	Investigative	[2]
L-739758	DM5IAXN	Discovery agent	N.A.	Investigative	[2]
L-746233	DMRC8MT	Discovery agent	N.A.	Investigative	[2]
L-750034	DM9QAP4	Discovery agent	N.A.	Investigative	[23]
L-756568	DMEQWSB	Discovery agent	N.A.	Investigative	[2]
L-767679	DM96SPJ	Discovery agent	N.A.	Investigative	[2]
N-(3,5-dichlorophenyl)imidodicarbonimidic diamide	DMQ0LF2	Discovery agent	N.A.	Investigative	[24]
RGDechi	DMX4JN6	Discovery agent	N.A.	Investigative	[12]
ROXIFIBAN	DMWUAMQ	Discovery agent	N.A.	Investigative	[2]
RWJ-53419	DMAEWMP	Discovery agent	N.A.	Investigative	[25]
SB-207043	DM704TL	Discovery agent	N.A.	Investigative	[7]
SB-265123	DM8UKH7	Discovery agent	N.A.	Investigative	[26]
SC-54701A	DM3BEKV	Discovery agent	N.A.	Investigative	[27]
ST-1646	DMR1G40	Discovery agent	N.A.	Investigative	[16]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Coronary artery disease	BA80-BA8Z	Peripheral blood	6.94E-01	-0.02	-0.17

References

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