Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT38RM1)

• DTT Name: Glycoprotein IIb/IIIa receptor (GPIIb/IIIa)
• Synonyms: Platelet membrane glycoprotein IIb; Platelet membrane glycoprotein IIIa; GP
• Gene Name: ITGA2B
• DTT Type: Successful target; [1]
• UniProt ID: ITA2B_HUMAN ; ITB3_HUMAN
• TTD ID: T50688
• Sequence:
  MARALCPLQALWLLEWVLLLLGPCAAPPAWALNLDPVQLTFYAGPNGSQFGFSLDFHKDS
  HGRVAIVVGAPRTLGPSQEETGGVFLCPWRAEGGQCPSLLFDLRDETRNVGSQTLQTFKA
  RQGLGASVVSWSDVIVACAPWQHWNVLEKTEEAEKTPVGSCFLAQPESGRRAEYSPCRGN
  TLSRIYVENDFSWDKRYCEAGFSSVVTQAGELVLGAPGGYYFLGLLAQAPVADIFSSYRP
  GILLWHVSSQSLSFDSSNPEYFDGYWGYSVAVGEFDGDLNTTEYVVGAPTWSWTLGAVEI
  LDSYYQRLHRLRGEQMASYFGHSVAVTDVNGDGRHDLLVGAPLYMESRADRKLAEVGRVY
  LFLQPRGPHALGAPSLLLTGTQLYGRFGSAIAPLGDLDRDGYNDIAVAAPYGGPSGRGQV
  LVFLGQSEGLRSRPSQVLDSPFPTGSAFGFSLRGAVDIDDNGYPDLIVGAYGANQVAVYR
  AQPVVKASVQLLVQDSLNPAVKSCVLPQTKTPVSCFNIQMCVGATGHNIPQKLSLNAELQ
  LDRQKPRQGRRVLLLGSQQAGTTLNLDLGGKHSPICHTTMAFLRDEADFRDKLSPIVLSL
  NVSLPPTEAGMAPAVVLHGDTHVQEQTRIVLDCGEDDVCVPQLQLTASVTGSPLLVGADN
  VLELQMDAANEGEGAYEAELAVHLPQGAHYMRALSNVEGFERLICNQKKENETRVVLCEL
  GNPMKKNAQIGIAMLVSVGNLEEAGESVSFQLQIRSKNSQNPNSKIVLLDVPVRAEAQVE
  LRGNSFPASLVVAAEEGEREQNSLDSWGPKVEHTYELHNNGPGTVNGLHLSIHLPGQSQP
  SDLLYILDIQPQGGLQCFPQPPVNPLKVDWGLPIPSPSPIHPAHHKRDRRQIFLPEPEQP
  SRLQDPVLVSCDSAPCTVVQCDLQEMARGQRAMVTVLAFLWLPSLYQRPLDQFVLQSHAW
  FNVSSLPYAVPPLSLPRGEAQVWTQLLRALEERAIPIWWVLVGVLGGLLLLTILVLAMWK
  VGFFKRNRPPLEEDDEEGE
• Function: Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It 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 cell surface.
• KEGG Pathway:
  Rap1 signaling pathway (hsa04015)
  PI3K-Akt signaling pathway (hsa04151)
  Focal adhesion (hsa04510)
  ECM-receptor interaction (hsa04512)
  Platelet activation (hsa04611)
  Neutrophil extracellular trap formation (hsa04613)
  Hematopoietic cell lineage (hsa04640)
  Regulation of actin cytoskeleton (hsa04810)
  Human papillomavirus infection (hsa05165)
  Pathways in cancer (hsa05200)
  Small cell lung cancer (hsa05222)
  Hypertrophic cardiomyopathy (hsa05410)
  Arrhythmogenic right ventricular cardiomyopathy (hsa05412)
  Dilated cardiomyopathy (hsa05414)
  Fluid shear stress and atherosclerosis (hsa05418)
• 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

4 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Abciximab	DMJO6GV	Acute disease		Approved	[2]
Eptifibatide	DMQXTJS	Acute cardiac ischemic events	BA40.Z	Approved	[3]
Hydroquinone	DM6AVR4	Melasma	ED60.1	Approved	[1]
Tirofiban	DMQG17S	Acute coronary syndrome	BA41	Approved	[2]

6 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
DMP-444	DMO7BQS	Coronary artery disease	BA80	Phase 3	[4]
99mTc-rBitistatin	DMFAMNH	Pulmonary embolism	JB42	Phase 1/2	[5]
AjvW2	DM6PN4H	Thrombosis	DB61-GB90	Phase 1	[6]
Lefradafiban	DMKZVLH	Angina pectoris	BA40	Phase 1	[7]
RGD-891	DMVJMF1	Thrombosis	DB61-GB90	Phase 1	[8]
SDZ-GPI-562	DMU9ZGN	Thrombosis	DB61-GB90	Phase 1	[9]

28 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LAMIFIBAN	DMHR1A7	Angina pectoris	BA40	Discontinued in Phase 3	[10]
LOTRAFIBAN	DMHE804	Cardiovascular disease	BA00-BE2Z	Discontinued in Phase 3	[11]
ORBOFIBAN	DMEDLXJ	Angina pectoris	BA40	Discontinued in Phase 3	[12]
SIBRAFIBAN	DMZU1TV	Angina pectoris	BA40	Discontinued in Phase 3	[13]
XEMILOFIBAN	DMBRYT8	Cardiovascular disease	BA00-BE2Z	Discontinued in Phase 3	[14]
Cromafiban	DMZLIUQ	Coronary artery disease	BA80	Discontinued in Phase 2	[15]
ELAROFIBAN	DM7TM91	Thrombosis	DB61-GB90	Discontinued in Phase 2	[16]
FK-633	DMQ3O4C	Artery stenosis	BD52	Discontinued in Phase 2	[17]
Gantofiban	DMHAM2J	Arteriosclerosis	BD40	Discontinued in Phase 2	[18]
MK-852	DMBJLZG	Thrombosis	DB61-GB90	Discontinued in Phase 2	[15]
SR-121787	DMCEQKG	Thrombosis	DB61-GB90	Discontinued in Phase 2	[19]
YM-337	DMCZIGQ	Angiogenesis disorder	BE2Z	Discontinued in Phase 2	[20]
ZD-2486	DMLFNMB	Angina pectoris	BA40	Discontinued in Phase 2	[15]
DMP-728	DMCK7LM	Thrombosis	DB61-GB90	Discontinued in Phase 1	[21]
FR-158999	DM5FW8Y	Thrombosis	DB61-GB90	Discontinued in Phase 1	[22]
L-734217	DMSB0J8	Thrombosis	DB61-GB90	Discontinued in Phase 1	[23]
ME-3277	DMUMSFR	Thrombosis	DB61-GB90	Discontinued in Phase 1	[24]
SC-52012	DMFC19E	Thrombosis	DB61-GB90	Discontinued in Phase 1	[25]
TAK-029	DMN02XD	Thrombosis	DB61-GB90	Discontinued in Phase 1	[26]
TP-9201	DMCV2KQ	Thrombosis	DB61-GB90	Discontinued in Phase 1	[27]
BIBU-251	DMMNI5K	Thrombosis	DB61-GB90	Terminated	[28]
Fradafiban	DMN4E5H	Thrombosis	DB61-GB90	Terminated	[29]
GR-144053	DMN8TH1	Thrombosis	DB61-GB90	Terminated	[30]
GR-233548	DMHM0EU	Thrombosis	DB61-GB90	Terminated	[2]
L-703014	DM47MKE	Thrombosis	DB61-GB90	Terminated	[31]
SB-208651	DMJD15H	Thrombosis	DB61-GB90	Terminated	[32]
SC-49992	DMY7KHW	Arterial thrombosis	DB61-DD30	Terminated	[33]
SKF-106760	DM7QPYK	Thrombosis	DB61-GB90	Terminated	[2]

3 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
RGD	DMFASRB	Discovery agent	N.A.	Investigative	[34]
RGD-039	DM0O9VG	Thrombosis	DB61-GB90	Investigative	[35]
XV454	DML1K07	Discovery agent	N.A.	Investigative	[36]

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	7.83E-01	-0.11	-0.45
Coronary artery disease	BA80-BA8Z	Peripheral blood	8.97E-01	0.1	0.39

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