Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTG0MT6)

• DTT Name: Interleukin-17 (IL17)
• Synonyms: Interleukin-17A; IL-17A; IL-17; Cytotoxic T-lymphocyte-associated antigen 8; Cytotoxic T lymphocyte-associated antigen 8; CTLA8; CTLA-8
• Gene Name: IL17A
• DTT Type: Successful target; [1]
• BioChemical Class: Cytokine: interleukin
• UniProt ID: IL17_HUMAN
• TTD ID: T22095
• Sequence:
  MTPGKTSLVSLLLLLSLEAIVKAGITIPRNPGCPNSEDKNFPRTVMVNLNIHNRNTNTNP
  KRSSDYYNRSTSPWNLHRNEDPERYPSVIWEAKCRHLGCINADGNVDYHMNSVPIQQEIL
  VLRREPPHCPNSFRLEKILVSVGCTCVTPIVHHVA
• Function: The heterodimer formed by IL17A and IL17F is a ligand for the heterodimeric complex formed by IL17RA and IL17RC. Involved in inducing stromal cells to produce proinflammatory and hematopoietic cytokines. Ligand for IL17RA and IL17RC.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Inflammatory bowel disease (IBD) (hsa05321)
  Rheumatoid arthritis (hsa05323)
• Reactome Pathway:
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)
  SARS-CoV-2 activates/modulates innate and adaptive immune responses (R-HSA-9705671)
  Interleukin-17 signaling (R-HSA-448424)

Molecular Interaction Atlas (MIA) of This DTT

3 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Bimekizumab	DMR9TF1	Plaque psoriasis	EA90.0	Approved	[2]
Brodalumab	DMASDQ6	Plaque psoriasis	EA90.0	Approved	[3]
Ixekizumab	DMXW92T	Plaque psoriasis	EA90.0	Approved	[1]

8 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ABT-122	DM23UQ9	Psoriatic arthritis	FA21	Phase 2	[4]
CJM112	DMTSVJM	Acne vulgaris	ED80	Phase 2	[5]
CNTO-6785	DM6RQXB	Rheumatoid arthritis	FA20	Phase 2	[6]
COVA322	DM824EG	Psoriasis vulgaris	EA90	Phase 1/2a	[7]
SHR-1314	DMADNY3	Plaque psoriasis	EA90.0	Phase 1/2	[2]
ABBV-257	DMCZI8L	Rheumatoid arthritis	FA20	Phase 1	[8]
ALX-0761	DMJ8ACF	Psoriasis vulgaris	EA90	Phase 1	[7]
SCH-900117	DM7A6R5	Rheumatoid arthritis	FA20	Phase 1	[9]

2 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
RG-4934	DMOI037	Arthritis	FA20	Discontinued in Phase 1	[10]
RO7040547	DMP0YNU	Asthma	CA23	Discontinued in Phase 1	[11]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Rheumatoid arthritis	FA20	Synovial tissue	2.91E-02	-0.16	-0.69

References

• [1] Brodalumab and ixekizumab, anti-interleukin-17-receptor antibodies for psoriasis: a critical appraisal. Br J Dermatol. 2012 Oct;167(4):710-3; discussion 714-5.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [4] DOI: 10.1136/annrheumdis-2015-eular.4042
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Targeting the IL-17-T(H)17 pathway. Nat Rev Drug Discov. 2015 Jan;14(1):11-2.
• [7] Bispecific antibodies rise again. Nat Rev Drug Discov. 2014 Nov;13(11):799-801.
• [8] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [9] Targeting IL-17 and TH17 cells in chronic inflammation. Nat Rev Drug Discov. 2012 Oct;11(10):763-76.
• [10] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800032677)
• [11] Bispecific antibodies: a mechanistic review of the pipeline. Nat Rev Drug Discov. 2019 Aug;18(8):585-608.