Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTIJWR7)

• DTT Name: Integrin beta-2 (ITGB2)
• Synonyms: MFI7; Integrin alpha-M/beta-2; Complement receptor C3 subunit beta; Cell surface adhesion glycoproteins LFA-1/CR3/p150,95 subunit beta; CD18
• Gene Name: ITGB2
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Integrin
• UniProt ID: ITB2_HUMAN
• TTD ID: T10513
• Sequence:
  MLGLRPPLLALVGLLSLGCVLSQECTKFKVSSCRECIESGPGCTWCQKLNFTGPGDPDSI
  RCDTRPQLLMRGCAADDIMDPTSLAETQEDHNGGQKQLSPQKVTLYLRPGQAAAFNVTFR
  RAKGYPIDLYYLMDLSYSMLDDLRNVKKLGGDLLRALNEITESGRIGFGSFVDKTVLPFV
  NTHPDKLRNPCPNKEKECQPPFAFRHVLKLTNNSNQFQTEVGKQLISGNLDAPEGGLDAM
  MQVAACPEEIGWRNVTRLLVFATDDGFHFAGDGKLGAILTPNDGRCHLEDNLYKRSNEFD
  YPSVGQLAHKLAENNIQPIFAVTSRMVKTYEKLTEIIPKSAVGELSEDSSNVVQLIKNAY
  NKLSSRVFLDHNALPDTLKVTYDSFCSNGVTHRNQPRGDCDGVQINVPITFQVKVTATEC
  IQEQSFVIRALGFTDIVTVQVLPQCECRCRDQSRDRSLCHGKGFLECGICRCDTGYIGKN
  CECQTQGRSSQELEGSCRKDNNSIICSGLGDCVCGQCLCHTSDVPGKLIYGQYCECDTIN
  CERYNGQVCGGPGRGLCFCGKCRCHPGFEGSACQCERTTEGCLNPRRVECSGRGRCRCNV
  CECHSGYQLPLCQECPGCPSPCGKYISCAECLKFEKGPFGKNCSAACPGLQLSNNPVKGR
  TCKERDSEGCWVAYTLEQQDGMDRYLIYVDESRECVAGPNIAAIVGGTVAGIVLIGILLL
  VIWKALIHLSDLREYRRFEKEKLKSQWNNDNPLFKSATTTVMNPKFAES
• Function: Integrin ITGAL/ITGB2 is also a receptor for the secreted form of ubiquitin-like protein ISG15; the interaction is mediated by ITGAL. Integrins ITGAM/ITGB2 and ITGAX/ITGB2 are receptors for the iC3b fragment of the third complement component and for fibrinogen. Integrin ITGAX/ITGB2 recognizes the sequence G-P-R in fibrinogen alpha-chain. Integrin ITGAM/ITGB2 recognizes P1 and P2 peptides of fibrinogen gamma chain. Integrin ITGAM/ITGB2 is also a receptor for factor X. Integrin ITGAD/ITGB2 is a receptor for ICAM3 and VCAM1. Contributes to natural killer cell cytotoxicity. Involved in leukocyte adhesion and transmigration of leukocytes including T-cells and neutrophils. Triggers neutrophil transmigration during lung injury through PTK2B/PYK2-mediated activation. Integrin ITGAL/ITGB2 in association with ICAM3, contributes to apoptotic neutrophil phagocytosis by macrophages. In association with alpha subunit ITGAM/CD11b, required for CD177-PRTN3-mediated activation of TNF primed neutrophils. Integrin ITGAL/ITGB2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4.
• KEGG Pathway:
  Rap1 signaling pathway (hsa04015)
  Phagosome (hsa04145)
  Hippo signaling pathway (hsa04390)
  Cell adhesion molecules (CAMs) (hsa04514)
  Natural killer cell mediated cytotoxicity (hsa04650)
  Leukocyte transendothelial migration (hsa04670)
  Regulation of actin cytoskeleton (hsa04810)
  Pertussis (hsa05133)
  Legionellosis (hsa05134)
  Leishmaniasis (hsa05140)
  Malaria (hsa05144)
  Amoebiasis (hsa05146)
  Staphylococcus aureus infection (hsa05150)
  Tuberculosis (hsa05152)
  HTLV-I infection (hsa05166)
  Rheumatoid arthritis (hsa05323)
  Viral myocarditis (hsa05416)
• Reactome Pathway:
  Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)
  Cell surface interactions at the vascular wall (R-HSA-202733)
  Integrin cell surface interactions (R-HSA-216083)
  Toll Like Receptor 4 (TLR4) Cascade (R-HSA-166016)

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
RP-L201	DMKVMWO	Leukocyte adhesion deficiency type 1	4A00.0Y	Phase 1/2	[2]

3 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BMS-587101	DMS2IC9	Psoriasis vulgaris	EA90	Discontinued in Phase 2	[3]
UK-279,276	DM4FZWP	Stroke	8B20	Discontinued in Phase 2	[1]
MLN-2201	DMQA5JW	Cerebrovascular ischaemia	8B1Z	Discontinued in Phase 1	[4]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
A-286982	DM98VFW	Discovery agent	N.A.	Investigative	[5]

References

• [1] Advances in ischemic stroke treatment: neuroprotective and combination therapies. Expert Opin Emerg Drugs. 2007 Mar;12(1):97-112.
• [2] Clinical pipeline report, company report or official report of Rocket Pharmaceuticals.
• [3] Discovery and development of 5-[(5S,9R)-9-(4-cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]non-7-yl-methyl]-3-thioph... J Med Chem. 2006 Nov 30;49(24):6946-9.
• [4] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010178)
• [5] Novel p-arylthio cinnamides as antagonists of leukocyte function-associated antigen-1/intracellular adhesion molecule-1 interaction. 2. Mechanism o... J Med Chem. 2001 Apr 12;44(8):1202-10.