Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: B-cell-activating factor (TNFSF13B)
• Synonyms: ZTNF4; UNQ401/PRO738; Tumor necrosis factor ligand superfamily member 13B; TNFSF20; TNF-and APOL-related leukocyte expressed ligand 1; TNF- and APOL-related leukocyte expressed ligand 1; TALL1; TALL-1; Dendritic cell-derived TNF-like molecule; CD257; BLyS; BAFF; B lymphocyte stimulator; B cell-activating factor
• Gene Name: TNFSF13B
• DTT Type: Successful target; [1]
• BioChemical Class: Cytokine: tumor necrosis factor
• UniProt ID: TN13B_HUMAN
• TTD ID: T02318
• Sequence:
  MDDSTEREQSRLTSCLKKREEMKLKECVSILPRKESPSVRSSKDGKLLAATLLLALLSCC
  LTVVSFYQVAALQGDLASLRAELQGHHAEKLPAGAGAPKAGLEEAPAVTAGLKIFEPPAP
  GEGNSSQNSRNKRAVQGPEETVTQDCLQLIADSETPTIQKGSYTFVPWLLSFKRGSALEE
  KENKILVKETGYFFIYGQVLYTDKTYAMGHLIQRKKVHVFGDELSLVTLFRCIQNMPETL
  PNNSCYSAGIAKLEEGDELQLAIPRENAQISLDGDVTFFGALKLL
• Function: TNFSF13/APRIL binds to the same 2 receptors. Together, they form a 2 ligands -2 receptors pathway involved in the stimulation of B- and T-cell function and the regulation of humoral immunity. A third B-cell specific BAFF-receptor (BAFFR/BR3) promotes the survival of mature B-cells and the B-cell response. Cytokine that binds to TNFRSF13B/TACI and TNFRSF17/BCMA.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  NF-kappa B signaling pathway (hsa04064)
  Intestinal immune network for IgA production (hsa04672)
  Rheumatoid arthritis (hsa05323)
• Reactome Pathway:
  TNFs bind their physiological receptors (R-HSA-5669034)
  TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway (R-HSA-5676594)
  TNFR2 non-canonical NF-kB pathway (R-HSA-5668541)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Belimumab	DM3OBQF	Membranous glomerulonephritis		Approved	[1]

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Blisibimod	DM7V9LH	Systemic lupus erythematosus	4A40.0	Phase 3	[2]
Tabalumab	DMKSAG1	Multiple myeloma	2A83	Phase 3	[3]
AMG 570	DMY1XJH	Systemic lupus erythematosus	4A40.0	Phase 2	[4]

2 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BR3-Fc	DMFN1WI	Idiopathic thrombocytopenic purpura	3B64.10	Discontinued in Phase 2	[5]
LymphoRad-131	DMDUM0Z	Lymphoma	2A80-2A86	Discontinued in Phase 1	[6]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1,4-Diethylene Dioxide	DMI36WC	Discovery agent	N.A.	Investigative	[7]
Receptor-Fc fusion proteins	DM4B6FO	Discovery agent	N.A.	Investigative	[8]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Multiple myeloma	2C82	Bone marrow	4.51E-01	0.04	0.09
Rheumatoid arthritis	FA20	Synovial tissue	4.50E-01	0.1	0.1

References

• [1] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] Tabalumab, an anti-BAFF monoclonal antibody, in patients with active rheumatoid arthritis with an inadequate response to TNF inhibitors. Ann Rheum Dis. 2013 Sep 1;72(9):1461-8.
• [4] Development of an ICOSL and BAFF bispecific inhibitor AMG 570 for systemic lupus erythematosus treatment. Clin Exp Rheumatol. Nov-Dec 2019;37(6):906-914.
• [5] Emerging drugs for idiopathic thrombocytopenic purpura in adults. Expert Opin Emerg Drugs. 2008 Jun;13(2):237-54.
• [6] Fusion Toxin BLyS-Gelonin Inhibits Growth of Malignant Human B Cell Lines In Vitro and In Vivo. PLoS One. 2012; 7(10): e47361.
• [7] DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41.
• [8] BAFF: B cell survival factor and emerging therapeutic target for autoimmune disorders. Expert Opin Ther Targets. 2003 Feb;7(1):115-23.