Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTJMF9P)

DTT Name ITGA4 messenger RNA (ITGA4 mRNA)
Synonyms
VLA4 subunit alpha (mRNA); VLA-4 subunit alpha (mRNA); Integrin alphaIV (mRNA); Integrin alpha4 (mRNA); Integrin alpha-IV (mRNA); Integrin alpha-4 (mRNA); CD49d (mRNA); CD49 antigenlike family member D (mRNA); CD49 antigen-like family member D (mRNA)
Gene Name ITGA4
DTT Type
Clinical trial target
 [1]
BioChemical Class
mRNA target
UniProt ID
ITA4_HUMAN
TTD ID
T78892
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MAWEARREPGPRRAAVRETVMLLLCLGVPTGRPYNVDTESALLYQGPHNTLFGYSVVLHS
HGANRWLLVGAPTANWLANASVINPGAIYRCRIGKNPGQTCEQLQLGSPNGEPCGKTCLE
ERDNQWLGVTLSRQPGENGSIVTCGHRWKNIFYIKNENKLPTGGCYGVPPDLRTELSKRI
APCYQDYVKKFGENFASCQAGISSFYTKDLIVMGAPGSSYWTGSLFVYNITTNKYKAFLD
KQNQVKFGSYLGYSVGAGHFRSQHTTEVVGGAPQHEQIGKAYIFSIDEKELNILHEMKGK
KLGSYFGASVCAVDLNADGFSDLLVGAPMQSTIREEGRVFVYINSGSGAVMNAMETNLVG
SDKYAARFGESIVNLGDIDNDGFEDVAIGAPQEDDLQGAIYIYNGRADGISSTFSQRIEG
LQISKSLSMFGQSISGQIDADNNGYVDVAVGAFRSDSAVLLRTRPVVIVDASLSHPESVN
RTKFDCVENGWPSVCIDLTLCFSYKGKEVPGYIVLFYNMSLDVNRKAESPPRFYFSSNGT
SDVITGSIQVSSREANCRTHQAFMRKDVRDILTPIQIEAAYHLGPHVISKRSTEEFPPLQ
PILQQKKEKDIMKKTINFARFCAHENCSADLQVSAKIGFLKPHENKTYLAVGSMKTLMLN
VSLFNAGDDAYETTLHVKLPVGLYFIKILELEEKQINCEVTDNSGVVQLDCSIGYIYVDH
LSRIDISFLLDVSSLSRAEEDLSITVHATCENEEEMDNLKHSRVTVAIPLKYEVKLTVHG
FVNPTSFVYGSNDENEPETCMVEKMNLTFHVINTGNSMAPNVSVEIMVPNSFSPQTDKLF
NILDVQTTTGECHFENYQRVCALEQQKSAMQTLKGIVRFLSKTDKRLLYCIKADPHCLNF
LCNFGKMESGKEASVHIQLEGRPSILEMDETSALKFEIRATGFPEPNPRVIELNKDENVA
HVLLEGLHHQRPKRYFTIVIISSSLLLGLIVLLLISYVMWKAGFFKRQYKSILQEENRRD
SWSYINSKSNDD
Function
Integrins alpha-4/beta-1 (VLA-4) and alpha-4/beta-7 are receptors for fibronectin. They recognize one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. They are also receptors for VCAM1. Integrin alpha-4/beta-1 recognizes the sequence Q-I-D-S in VCAM1. Integrin alpha-4/beta-7 is also a receptor for MADCAM1. It recognizes the sequence L-D-T in MADCAM1. On activated endothelial cells integrin VLA-4 triggers homotypic aggregation for most VLA-4-positive leukocyte cell lines. It may also participate in cytolytic T-cell interactions with target cells. ITGA4:ITGB1 binds to fractalkine (CX3CL1) and may act as its coreceptor in CX3CR1-dependent fractalkine signaling. ITGA4:ITGB1 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.
KEGG Pathway
PI3K-Akt signaling pathway (hsa04151 )
Focal adhesion (hsa04510 )
ECM-receptor interaction (hsa04512 )
Cell adhesion molecules (CAMs) (hsa04514 )
Hematopoietic cell lineage (hsa04640 )
Leukocyte transendothelial migration (hsa04670 )
Intestinal immune network for IgA production (hsa04672 )
Regulation of actin cytoskeleton (hsa04810 )
Leishmaniasis (hsa05140 )
Hypertrophic cardiomyopathy (HCM) (hsa05410 )
Arrhythmogenic right ventricular cardiomyopathy (ARVC) (hsa05412 )
Dilated cardiomyopathy (hsa05414 )
Reactome Pathway
Cell surface interactions at the vascular wall (R-HSA-202733 )
Integrin cell surface interactions (R-HSA-216083 )
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
1 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
ATL1102 DM3POT6 Multiple sclerosis 8A40 Phase 2 [1]
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6 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
ISIS 24448 DMLHQ2J Discovery agent N.A. Investigative [2]
ISIS 24453 DM45WUZ Discovery agent N.A. Investigative [2]
ISIS 24454 DMDE3J1 Discovery agent N.A. Investigative [2]
ISIS 24475 DMBKZOQ Discovery agent N.A. Investigative [2]
ISIS 24477 DMCNBIL Discovery agent N.A. Investigative [2]
MK-0668 DMVBFJP Discovery agent N.A. Investigative [3]
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⏷ Show the Full List of 6 Investigative Drug(s)

References

1 CD49d antisense drug ATL1102 reduces disease activity in patients with relapsing-remitting MS.Neurology.2014 Nov 11;83(20):1780-8.
2 US patent application no. 6,258,790, Antisense modulation of integrin .alpha.4 expression.
3 Discovery of N-{N-[(3-cyanobenzene) sulfonyl]-4(R)-(3,3-difluoropiperidin-1-yl)-(l)-prolyl}-4-[(3',5'-dichloro-isonicotinoyl) amino]-(l)-phenylalan... Bioorg Med Chem Lett. 2009 Oct 1;19(19):5803-6.