Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTA5MS9)

• DTT Name: TNF related apoptosis inducing ligand (TNFSF10)
• Synonyms: Tumor necrosis factor ligand superfamily member 10; TRAIL; TNF-related apoptosis-inducing ligand; Protein TRAIL; CD253; Apo-2L; Apo-2 ligand; APO2L
• Gene Name: TNFSF10
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Cytokine: tumor necrosis factor
• UniProt ID: TNF10_HUMAN
• TTD ID: T46084
• Sequence:
  MAMMEVQGGPSLGQTCVLIVIFTVLLQSLCVAVTYVYFTNELKQMQDKYSKSGIACFLKE
  DDSYWDPNDEESMNSPCWQVKWQLRQLVRKMILRTSEETISTVQEKQQNISPLVRERGPQ
  RVAAHITGTRGRSNTLSSPNSKNEKALGRKINSWESSRSGHSFLSNLHLRNGELVIHEKG
  FYYIYSQTYFRFQEEIKENTKNDKQMVQYIYKYTSYPDPILLMKSARNSCWSKDAEYGLY
  SIYQGGIFELKENDRIFVSVTNEHLIDMDHEASFFGAFLVG
• Function: Induces apoptosis. Its activity may be modulated by binding to the decoy receptors TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4 and TNFRSF11B/OPG that cannot induce apoptosis. Cytokine that binds to TNFRSF10A/TRAILR1, TNFRSF10B/TRAILR2, TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4 and possibly also to TNFRSF11B/OPG.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  FoxO signaling pathway (hsa04068)
  Apoptosis (hsa04210)
  Natural killer cell mediated cytotoxicity (hsa04650)
  Measles (hsa05162)
  Influenza A (hsa05164)
• Reactome Pathway:
  Regulation by c-FLIP (R-HSA-3371378)
  RIPK1-mediated regulated necrosis (R-HSA-5213460)
  CASP8 activity is inhibited (R-HSA-5218900)
  Dimerization of procaspase-8 (R-HSA-69416)
  TRAIL signaling (R-HSA-75158)
  Ligand-dependent caspase activation (R-HSA-140534)

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
ABBV-621	DM90EO3	Haematological malignancy	2B33.Y	Phase 1	[2]
Ad5-TRAIL	DM2UMGE	Prostate cancer	2C82.0	Phase 1	[3]
DA-3607	DM4JG0B	Brain cancer	2A00	Phase 1	[1]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Nimesulide	DMR1NMD	Metastatic colorectal cancer	2B91	Terminated	[4]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Neuroectodermal tumour	2C82	Nervous tissue	4.40E-01	-0.16	-0.18
Rectal cancer	2C82	Rectal colon tissue	1.16E-05	-1.09	-3.9
Prostate cancer	2C82	Prostate	9.66E-01	0.18	0.37

References

• [1] Cancer gene therapy using a novel secretable trimeric TRAIL. Gene Ther. 2006 Feb;13(4):330-8.
• [2] Clinical pipeline report, company report or official report of AbbVie.
• [3] Enhancement of Ad5-TRAIL cytotoxicity against renal cell carcinoma with histone deacetylase inhibitors. Cancer Gene Ther. 2006 Jun;13(6):628-32.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.