Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTBRJS9)

• DTT Name: Inhibitory receptor SHPS-1 (SIRPA)
• Synonyms: SHP substrate 1; SHPS-1; Brain Ig-like molecule with tyrosine-based activation motifs; Bit; CD172 antigen-like family member A; Macrophage fusion receptor; MyD-1 antigen; Signal-regulatory protein alpha-1; Sirp-alpha-1; Signal-regulatory protein alpha-2; Sirp-alpha-2; Signal-regulatory protein alpha-3; Sirp-alpha-3; p84; DE AltName: CD_antigen=CD172a
• Gene Name: SIRPA
• DTT Type: Clinical trial target; [1]
• UniProt ID: SHPS1_HUMAN
• TTD ID: T46789
• Sequence:
  MEPAGPAPGRLGPLLCLLLAASCAWSGVAGEEELQVIQPDKSVLVAAGETATLRCTATSL
  IPVGPIQWFRGAGPGRELIYNQKEGHFPRVTTVSDLTKRNNMDFSIRIGNITPADAGTYY
  CVKFRKGSPDDVEFKSGAGTELSVRAKPSAPVVSGPAARATPQHTVSFTCESHGFSPRDI
  TLKWFKNGNELSDFQTNVDPVGESVSYSIHSTAKVVLTREDVHSQVICEVAHVTLQGDPL
  RGTANLSETIRVPPTLEVTQQPVRAENQVNVTCQVRKFYPQRLQLTWLENGNVSRTETAS
  TVTENKDGTYNWMSWLLVNVSAHRDDVKLTCQVEHDGQPAVSKSHDLKVSAHPKEQGSNT
  AAENTGSNERNIYIVVGVVCTLLVALLMAALYLVRIRQKKAQGSTSSTRLHEPEKNAREI
  TQDTNDITYADLNLPKGKKPAPQAAEPNNHTEYASIQTSPQPASEDTLTYADLDMVHLNR
  TPKQPAPKPEPSFSEYASVQVPRK
• Function: Immunoglobulin-like cell surface receptor for CD47. Acts as docking protein and induces translocation of PTPN6, PTPN11 and other binding partners from the cytosol to the plasma membrane. Supports adhesion of cerebellar neurons, neurite outgrowth and glial cell attachment. May play a key role in intracellular signaling during synaptogenesis and in synaptic function (By similarity). Involved in the negative regulation of receptor tyrosine kinase-coupled cellular responses induced by cell adhesion, growth factors or insulin. Mediates negative regulation of phagocytosis, mast cell activation and dendritic cell activation. CD47 binding prevents maturation of immature dendritic cells and inhibits cytokine production by mature dendritic cells.
• KEGG Pathway: Osteoclast differentiation (hsa04380)
• Reactome Pathway:
  Signal regulatory protein family interactions (R-HSA-391160)
  Neutrophil degranulation (R-HSA-6798695)
  Cell surface interactions at the vascular wall (R-HSA-202733)

Molecular Interaction Atlas (MIA) of This DTT

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BI 765063	DMZMAOW	Solid tumour/cancer	2A00-2F9Z	Phase 1	[1]
CC-95251	DM7E1W0	Solid tumour/cancer	2A00-2F9Z	Phase 1	[2]
FSI-189	DMPENAL	Non-hodgkin lymphoma	2B33.5	Phase 1	[3]

References

• [1] Clinical pipeline report, company report or official report of OSE Immunotherapeutics.
• [2] ClinicalTrials.gov (NCT03783403) A Study of CC-95251, a Monoclonal Antibody Directed Against SIRPalpha, in Subjects With Advanced Solid and Hematologic Cancers. U.S. National Institutes of Health.
• [3] T cells bring unconventional cancer-targeting to the clinic - again. Nat Biotechnol. 2020 Apr;38(4):389-391.