Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTT0Q1F)

• DTT Name: Interleukin-10 (IL10)
• Synonyms: IL-10; Cytokine synthesis inhibitory factor; CSIF
• Gene Name: IL10
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Cytokine: interleukin
• UniProt ID: IL10_HUMAN
• TTD ID: T09092
• Sequence:
  MHSSALLCCLVLLTGVRASPGQGTQSENSCTHFPGNLPNMLRDLRDAFSRVKTFFQMKDQ
  LDNLLLKESLLEDFKGYLGCQALSEMIQFYLEEVMPQAENQDPDIKAHVNSLGENLKTLR
  LRLRRCHRFLPCENKSKAVEQVKNAFNKLQEKGIYKAMSEFDIFINYIEAYMTMKIRN
• Function: Mechanistically, IL10 binds to its heterotetrameric receptor comprising IL10RA and IL10RB leading to JAK1 and STAT2-mediated phosphorylation of STAT3. In turn, STAT3 translocates to the nucleus where it drives expression of anti-inflammatory mediators. Targets antigen-presenting cells (APCs) such as macrophages and monocytes and inhibits their release of pro-inflammatory cytokines including granulocyte-macrophage colony-stimulating factor /GM-CSF, granulocyte colony-stimulating factor/G-CSF, IL-1 alpha, IL-1 beta, IL-6, IL-8 and TNF-alpha. Interferes also with antigen presentation by reducing the expression of MHC-class II and co-stimulatory molecules, thereby inhibiting their ability to induce T cell activation. In addition, controls the inflammatory response of macrophages by reprogramming essential metabolic pathways including mTOR signaling. Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  FoxO signaling pathway (hsa04068)
  Jak-STAT signaling pathway (hsa04630)
  T cell receptor signaling pathway (hsa04660)
  Intestinal immune network for IgA production (hsa04672)
  Pertussis (hsa05133)
  Leishmaniasis (hsa05140)
  Chagas disease (American trypanosomiasis) (hsa05142)
  African trypanosomiasis (hsa05143)
  Malaria (hsa05144)
  Toxoplasmosis (hsa05145)
  Amoebiasis (hsa05146)
  Staphylococcus aureus infection (hsa05150)
  Tuberculosis (hsa05152)
  Epstein-Barr virus infection (hsa05169)
  Asthma (hsa05310)
  Autoimmune thyroid disease (hsa05320)
  Inflammatory bowel disease (IBD) (hsa05321)
  Systemic lupus erythematosus (hsa05322)
  Allograft rejection (hsa05330)
• Reactome Pathway:
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)
  Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation (R-HSA-8950505)
  CD163 mediating an anti-inflammatory response (R-HSA-9662834)
  FCGR3A-mediated IL10 synthesis (R-HSA-9664323)
  Interleukin-10 signaling (R-HSA-6783783)

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
AM0010	DMGMNUE	Pancreatic cancer	2C10	Phase 3	[2]
F-8-IL-10 fusion protein	DMBFPO1	Endometriosis	GA10	Phase 2	[1]
Ilodecakin	DMDNHRA	Sarcoidosis	4B20.5	Phase 2	[3]
XT-150	DMCYM9Q	Knee osteoarthritis	FA01	Phase 2	[4]
AG019	DMEN2L7	Type-1 diabetes	5A10	Phase 1/2	[5]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ankinara	DMZKC7S	Inflammatory bowel disease	DD72	Investigative	[6]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Psoriasis	EA90	Skin	7.19E-03	-0.11	-0.35
Endometriosis	GA10	Endometrium tissue	1.07E-02	0.08	0.56
Rheumatoid arthritis	FA20	Synovial tissue	3.51E-02	0.17	0.42

References

• [1] Preclinical characterization of DEKAVIL (F8-IL10), a novel clinical-stage immunocytokine which inhibits the progression of collagen-induced arthritis. Arthritis Res Ther. 2009;11(5):R142.
• [2] Clinical pipeline report, company report or official report of ARMO BioSciences.
• [3] Ilodecakin. Schering-Plough Corp. IDrugs. 1999 Oct;2(10):1045-58.
• [4] Clinical pipeline report, company report or official report of Xalud Therapeutics
• [5] ClinicalTrials.gov (NCT03751007) A Study to Assess the Safety and Tolerability of Different Doses of AG019 Administered Alone or in Combination With Teplizumab in Participants With Recently Diagnosed Type 1 Diabetes Mellitus (T1D). U.S. National Institutes of Health.
• [6] Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.