Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTC1GLB)

• DTT Name: Interleukin-23 (IL23)
• Synonyms: UNQ2498/PRO5798; SGRF; P40 subunit of interleukin-23; Interleukin-23 subunit p19; Interleukin-23 subunit alpha; Interleukin 23 subunit alpha; IL-23p19; IL-23-A; IL-23 subunit alpha; IL-23
• Gene Name: IL23A
• DTT Type: Successful target; [1]
• BioChemical Class: Cytokine: interleukin
• UniProt ID: IL23A_HUMAN
• TTD ID: T06841
• Sequence:
  MLGSRAVMLLLLLPWTAQGRAVPGGSSPAWTQCQQLSQKLCTLAWSAHPLVGHMDLREEG
  DEETTNDVPHIQCGDGCDPQGLRDNSQFCLQRIHQGLIFYEKLLGSDIFTGEPSLLPDSP
  VGQLHASLLGLSQLLQPEGHHWETQQIPSLSPSQPWQRLLLRFKILRSLQAFVAVAARVF
  AHGAATLSP
• Function: IL-23 may constitute with IL-17 an acute response to infection in peripheral tissues. IL-23 binds to a heterodimeric receptor complex composed of IL12RB1 and IL23R, activates the Jak-Stat signaling cascade, stimulates memory rather than naive T-cells and promotes production of proinflammatory cytokines. IL-23 induces autoimmune inflammation and thus may be responsible for autoimmune inflammatory diseases and may be important for tumorigenesis. Associates with IL12B to form the IL-23 interleukin, a heterodimeric cytokine which functions in innate and adaptive immunity.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Toll-like receptor signaling pathway (hsa04620)
  RIG-I-like receptor signaling pathway (hsa04622)
  Jak-STAT signaling pathway (hsa04630)
  Type I diabetes mellitus (hsa04940)
  Pertussis (hsa05133)
  Legionellosis (hsa05134)
  Leishmaniasis (hsa05140)
  Chagas disease (American trypanosomiasis) (hsa05142)
  African trypanosomiasis (hsa05143)
  Malaria (hsa05144)
  Toxoplasmosis (hsa05145)
  Amoebiasis (hsa05146)
  Tuberculosis (hsa05152)
  Measles (hsa05162)
  Influenza A (hsa05164)
  Herpes simplex infection (hsa05168)
  Inflammatory bowel disease (IBD) (hsa05321)
  Allograft rejection (hsa05330)
• Reactome Pathway:
  Interleukin-23 signaling (R-HSA-9020933)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)

Molecular Interaction Atlas (MIA) of This DTT

4 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CNTO-1959	DMPC2QY	Plaque psoriasis	EA90.0	Approved	[1]
Risankizumab	DMM32GT	Plaque psoriasis	EA90.0	Approved	[2]
Tildrakizumab	DMLW9HG	Plaque psoriasis	EA90.0	Approved	[3]
Ustekinumab	DMHTYK3	Plaque psoriasis	EA90.0	Approved	[4]

7 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ABP 654	DM0GXWT	Plaque psoriasis	EA90.0	Phase 3	[5]
BI 655066	DMBH4FL	Chronic plaque psoriasis	EA90.0	Phase 3	[6]
Brazikumab	DM4NWPE	Crohn disease	DD70	Phase 3	[7]
MK-3222	DMQBF7O	Hairy cell leukaemia	2A82.2	Phase 3	[8]
CNT0-1959	DMOR8SY	Rheumatoid arthritis	FA20	Phase 2	[1]
AMG-139	DMEHOVF	Crohn disease	DD70	Phase 1	[9]
mRNA-2752	DMUKBI2	Solid tumour/cancer	2A00-2F9Z	Phase 1	[10]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Psoriasis	EA90	Skin	9.54E-04	-0.07	-0.27
Rheumatoid arthritis	FA20	Synovial tissue	5.37E-01	-0.1	-0.42
Asthma	CA23	Nasal and bronchial airway	1.84E-01	-0.11	-0.37

References

• [1] Interleukin-23 in the pathogenesis and treatment of psoriasis. Skin Therapy Lett. 2015 Mar-Apr;20(2):1-4.
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [3] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [4] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [5] Clinical pipeline report, company report or official report of Amgen
• [6] Anti-IL-23A mAb BI 655066 for treatment of moderate-to-severe psoriasis: Safety, efficacy, pharmacokinetics, and biomarker results of a single-rising-dose, randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol. 2015 Jul;136(1):116-124.e7.
• [7] Blockade of IL-23: What is in the Pipeline? J Crohns Colitis. 2022 May 11;16(Supplement_2):ii64-ii72.
• [8] Tildrakizumab (MK-3222), an anti-interleukin-23p19 monoclonal antibody, improves psoriasis in a phase IIb randomized placebo-controlled trial. Br J Dermatol. 2015 Oct;173(4):930-9.
• [9] Preclinical development of AMG 139, a human antibody specifically targeting IL-23. Br J Pharmacol. 2015 Jan;172(1):159-72.
• [10] Clinical pipeline report, company report or official report of Moderna Therapeutics.