Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT7ZMI1)

• DTT Name: Integrin alpha-4/beta-7 (ITGA4/B7)
• Synonyms: alpha(4)beta(7) integrin; Alpha 4 beta 7 integrin
• Gene Name: ITGA4-ITGB7
• DTT Type: Successful target; [1]
• BioChemical Class: Integrin
• UniProt ID: ITA4_HUMAN-ITB7_HUMAN
• TTD ID: T07403
• Sequence:
  MVALPMVLVLLLVLSRGESELDAKIPSTGDATEWRNPHLSMLGSCQPAPSCQKCILSHPS
  CAWCKQLNFTASGEAEARRCARREELLARGCPLEELEEPRGQQEVLQDQPLSQGARGEGA
  TQLAPQRVRVTLRPGEPQQLQVRFLRAEGYPVDLYYLMDLSYSMKDDLERVRQLGHALLV
  RLQEVTHSVRIGFGSFVDKTVLPFVSTVPSKLRHPCPTRLERCQSPFSFHHVLSLTGDAQ
  AFEREVGRQSVSGNLDSPEGGFDAILQAALCQEQIGWRNVSRLLVFTSDDTFHTAGDGKL
  GGIFMPSDGHCHLDSNGLYSRSTEFDYPSVGQVAQALSAANIQPIFAVTSAALPVYQELS
  KLIPKSAVGELSEDSSNVVQLIMDAYNSLSSTVTLEHSSLPPGVHISYESQCEGPEKREG
  KAEDRGQCNHVRINQTVTFWVSLQATHCLPEPHLLRLRALGFSEELIVELHTLCDCNCSD
  TQPQAPHCSDGQGHLQCGVCSCAPGRLGRLCECSVAELSSPDLESGCRAPNGTGPLCSGK
  GHCQCGRCSCSGQSSGHLCECDDASCERHEGILCGGFGRCQCGVCHCHANRTGRACECSG
  DMDSCISPEGGLCSGHGRCKCNRCQCLDGYYGALCDQCPGCKTPCERHRDCAECGAFRTG
  PLATNCSTACAHTNVTLALAPILDDGWCKERTLDNQLFFFLVEDDARGTVVLRVRPQEKG
  ADHTQAIVLGCVGGIVAVGLGLVLAYRLSVEIYDRREYSRFEKEQQQLNWKQDSNPLYKS
  AITTTINPRFQEADSPTLMAWEARREPGPRRAAVRETVMLLLCLGVPTGRPYNVDTESAL
  LYQGPHNTLFGYSVVLHSHGANRWLLVGAPTANWLANASVINPGAIYRCRIGKNPGQTCE
  QLQLGSPNGEPCGKTCLEERDNQWLGVTLSRQPGENGSIVTCGHRWKNIFYIKNENKLPT
  GGCYGVPPDLRTELSKRIAPCYQDYVKKFGENFASCQAGISSFYTKDLIVMGAPGSSYWT
  GSLFVYNITTNKYKAFLDKQNQVKFGSYLGYSVGAGHFRSQHTTEVVGGAPQHEQIGKAY
  IFSIDEKELNILHEMKGKKLGSYFGASVCAVDLNADGFSDLLVGAPMQSTIREEGRVFVY
  INSGSGAVMNAMETNLVGSDKYAARFGESIVNLGDIDNDGFEDVAIGAPQEDDLQGAIYI
  YNGRADGISSTFSQRIEGLQISKSLSMFGQSISGQIDADNNGYVDVAVGAFRSDSAVLLR
  TRPVVIVDASLSHPESVNRTKFDCVENGWPSVCIDLTLCFSYKGKEVPGYIVLFYNMSLD
  VNRKAESPPRFYFSSNGTSDVITGSIQVSSREANCRTHQAFMRKDVRDILTPIQIEAAYH
  LGPHVISKRSTEEFPPLQPILQQKKEKDIMKKTINFARFCAHENCSADLQVSAKIGFLKP
  HENKTYLAVGSMKTLMLNVSLFNAGDDAYETTLHVKLPVGLYFIKILELEEKQINCEVTD
  NSGVVQLDCSIGYIYVDHLSRIDISFLLDVSSLSRAEEDLSITVHATCENEEEMDNLKHS
  RVTVAIPLKYEVKLTVHGFVNPTSFVYGSNDENEPETCMVEKMNLTFHVINTGNSMAPNV
  SVEIMVPNSFSPQTDKLFNILDVQTTTGECHFENYQRVCALEQQKSAMQTLKGIVRFLSK
  TDKRLLYCIKADPHCLNFLCNFGKMESGKEASVHIQLEGRPSILEMDETSALKFEIRATG
  FPEPNPRVIELNKDENVAHVLLEGLHHQRPKRYFTIVIISSSLLLGLIVLLLISYVMWKA
  GFFKRQYKSILQEENRRDSWSYINSKSNDD
• Function: It is expressed on lymphocytes and is responsible for T-cell homing into gut-associated lymphoid tissues through its binding to mucosal addressin cell adhesion molecule (MAdCAM), which is present on high endothelial venules of mucosal lymphoid organs.

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MLN0002	DMP2LZ8	Crohn disease	DD70	Approved	[1]

4 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MORF-057	DMS274E	Crohn disease	DD70	Phase 2	[2]
PN-943	DMUZLKW	Ulcerative colitis	DD71	Phase 2	[3]
TRK-170	DM13G5R	Inflammatory bowel disease	DD72	Phase 2	[4]
GS-1427	DMDDBG1	Inflammation	1A00-CA43.1	Phase 1	[5]

2 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
R1295	DMT8V9G	Rheumatoid arthritis	FA20	Discontinued in Phase 1	[6]
TR-14035	DMWD39E	Multiple sclerosis	8A40	Discontinued in Phase 1	[7]

References

• [1] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [2] ClinicalTrials.gov (NCT05291689) A Phase 2a, Open-label, Single-arm Study to Evaluate the Efficacy, Safety, and Tolerability of MORF-057 in Adults With Moderately to Severely Active Ulcerative Colitis (EMERALD-1). U.S.National Institutes of Health.
• [3] Single- and Multiple-Dose Pharmacokinetics and Pharmacodynamics of PN-943, a Gastrointestinal-Restricted Oral Peptide Antagonist of alpha4beta7, in Healthy Volunteers. Clin Pharmacol Drug Dev. 2021 Nov;10(11):1263-1278.
• [4] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [5] Clinical pipeline report, company report or official report of Gilead
• [6] Vedolizumab: an 47 integrin inhibitor for inflammatory bowel diseases.Ann Pharmacother.2014 Dec;48(12):1629-35.
• [7] Pharmacokinetics and metabolism of TR-14035, a novel antagonist of a4ss1/a4ss7 integrin mediated cell adhesion, in rat and dog. Xenobiotica. 2005 Apr;35(4):373-89.