Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTLRN4A)

• DTT Name: NKG2 D activating NK receptor (KLRK1)
• Synonyms: NKG2Dactivating NK receptor; NKG2D type II integral membrane protein; NKG2D; NKG2-D-activating NK receptor; NKG2-D type II integral membrane protein; NK cell receptor D; Killer cell lectinlike receptor subfamily K member 1; Killer cell lectin-like receptor subfamily K member 1; D12S2489E; CD314
• Gene Name: KLRK1
• DTT Type: Clinical trial target; [1]
• UniProt ID: NKG2D_HUMAN
• TTD ID: T35289
• Sequence:
  MGWIRGRRSRHSWEMSEFHNYNLDLKKSDFSTRWQKQRCPVVKSKCRENASPFFFCCFIA
  VAMGIRFIIMVAIWSAVFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNW
  YESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLT
  IIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTV
• Function: Provides both stimulatory and costimulatory innate immune responses on activated killer (NK) cells, leading to cytotoxic activity. Acts as a costimulatory receptor for T-cell receptor (TCR) in CD8(+) T-cell-mediated adaptive immune responses by amplifying T-cell activation. Stimulates perforin-mediated elimination of ligand-expressing tumor cells. Signaling involves calcium influx, culminating in the expression of TNF-alpha. Participates in NK cell-mediated bone marrow graft rejection. May play a regulatory role in differentiation and survival of NK cells. Binds to ligands belonging to various subfamilies of MHC class I-related glycoproteins including MICA, MICB, RAET1E, RAET1G, RAET1L/ULBP6, ULBP1, ULBP2, ULBP3 (ULBP2>ULBP1>ULBP3) and ULBP4. Function as an activating and costimulatory receptor involved in immunosurveillance upon binding to various cellular stress-inducible ligands displayed at the surface of autologous tumor cells and virus-infected cells.
• KEGG Pathway:
  Natural killer cell mediated cytotoxicity (hsa04650)
  Malaria (hsa05144)
• Reactome Pathway:
  DAP12 interactions (R-HSA-2172127)
  DAP12 signaling (R-HSA-2424491)
  Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DTT

5 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
NN8555	DM3IEHP	Crohn disease	DD70	Phase 2	[1]
CM-CS1 T-cell	DMY5V4U	Acute myeloid leukaemia	2A60	Phase 1	[2]
CYAD-101	DMSM42V	Colorectal cancer	2B91.Z	Phase 1	[3]
NKR-2 CAR-T Cells	DMDLJM1	Acute myeloid leukaemia	2A60	Phase 1	[4]
NKR-2 cells	DMR5ATX	Acute myeloid leukaemia	2A60	Phase 1	[5]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] ClinicalTrials.gov (NCT02203825) Safety Study of Chimeric Antigen Receptor Modified T-cells Targeting NKG2D-Ligands
• [3] ClinicalTrials.gov (NCT03692429) alloSHRINK - Standard cHemotherapy Regimen and Immunotherapy With Allogeneic NKG2D-based CYAD-101 Chimeric Antigen Receptor T-cells
• [4] ClinicalTrials.gov (NCT03612739) EPITHINK: Epigenetic Drug Treatment and Therapeutic Immunotherapy With NKR-2
• [5] ClinicalTrials.gov (NCT03310008) Dose Escalation and Dose Expansion Phase I Study to Assess the Safety and Clinical Activity of Multiple Doses of NKR-2 Administered Concurrently With FOLFOX in Colorectal Cancer With Potentially Resectable Liver Metastases