Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT5UT28)

• DTT Name: Semaphorin-4D (SEMA4D)
• Synonyms: SEMAJ; GR3; CD100; C9orf164; BB18; A8
• Gene Name: SEMA4D
• DTT Type: Clinical trial target; [1]
• UniProt ID: SEM4D_HUMAN
• TTD ID: T50823
• Sequence:
  MRMCTPIRGLLMALAVMFGTAMAFAPIPRITWEHREVHLVQFHEPDIYNYSALLLSEDKD
  TLYIGAREAVFAVNALNISEKQHEVYWKVSEDKKAKCAEKGKSKQTECLNYIRVLQPLSA
  TSLYVCGTNAFQPACDHLNLTSFKFLGKNEDGKGRCPFDPAHSYTSVMVDGELYSGTSYN
  FLGSEPIISRNSSHSPLRTEYAIPWLNEPSFVFADVIRKSPDSPDGEDDRVYFFFTEVSV
  EYEFVFRVLIPRIARVCKGDQGGLRTLQKKWTSFLKARLICSRPDSGLVFNVLRDVFVLR
  SPGLKVPVFYALFTPQLNNVGLSAVCAYNLSTAEEVFSHGKYMQSTTVEQSHTKWVRYNG
  PVPKPRPGACIDSEARAANYTSSLNLPDKTLQFVKDHPLMDDSVTPIDNRPRLIKKDVNY
  TQIVVDRTQALDGTVYDVMFVSTDRGALHKAISLEHAVHIIEETQLFQDFEPVQTLLLSS
  KKGNRFVYAGSNSGVVQAPLAFCGKHGTCEDCVLARDPYCAWSPPTATCVALHQTESPSR
  GLIQEMSGDASVCPDKSKGSYRQHFFKHGGTAELKCSQKSNLARVFWKFQNGVLKAESPK
  YGLMGRKNLLIFNLSEGDSGVYQCLSEERVKNKTVFQVVAKHVLEVKVVPKPVVAPTLSV
  VQTEGSRIATKVLVASTQGSSPPTPAVQATSSGAITLPPKPAPTGTSCEPKIVINTVPQL
  HSEKTMYLKSSDNRLLMSLFLFFFVLFLCLFFYNCYKGYLPRQCLKFRSALLIGKKKPKS
  DFCDREQSLKETLVEPGSFSQQNGEHPKPALDTGYETEQDTITSKVPTDREDSQRIDDLS
  ARDKPFDVKCELKFADSDADGD
• Function: Regulates GABAergic synapse development. Promotes the development of inhibitory synapses in a PLXNB1-dependent manner. Modulates the complexity and arborization of developing neurites in hippocampal neurons by activating PLXNB1 and interaction with PLXNB1 mediates activation of RHOA. Promotes the migration of cerebellar granule cells. Plays a role in the immune system; induces B-cells to aggregate and improves their viability (in vitro). Induces endothelial cell migration through the activation of PTK2B/PYK2, SRC, and the phosphatidylinositol 3-kinase-AKT pathway. Cell surface receptor for PLXNB1 and PLXNB2 that plays an important role in cell-cell signaling.
• KEGG Pathway: Axon guidance (hsa04360)
• Reactome Pathway:
  Sema4D induced cell migration and growth-cone collapse (R-HSA-416572)
  Other semaphorin interactions (R-HSA-416700)
  Sema4D mediated inhibition of cell attachment and migration (R-HSA-416550)

Molecular Interaction Atlas (MIA) of This DTT

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
VX-15	DMLWM4G	Huntington disease	8A01.10	Phase 2	[1]
Pepinemab	DM03GDJ	Squamous head and neck cell carcinom	2D60.0	Phase 1/2	[2]

References

• [1] Safety, Pharmacokinetics, and Pharmacodynamics of a Humanized Anti-Semaphorin 4D Antibody, in a First-In-Human Study of Patients with Advanced Soli... Clin Cancer Res. 2016 Feb 15;22(4):827-36.
• [2] Clinical pipeline report, company report or official report of Vaccinex.