Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTCTE1G)

• DTT Name: Interleukin-8 (IL8)
• Synonyms: T-cell chemotactic factor; Protein 3-10C; Neutrophil-activating protein 1; NAP-1; Monocyte-derived neutrophil-activating peptide; Monocyte-derived neutrophil chemotactic factor; MONAP; MDNCF; IL8; IL-8; Granulocyte chemotactic protein 1; GCP-1; Emoctakin; Chemokine (C-X-C motif) ligand 8; C-X-C motif chemokine 8
• Gene Name: CXCL8
• DTT Type: Successful target; [1]
• BioChemical Class: Cytokine: interleukin
• UniProt ID: IL8_HUMAN
• TTD ID: T22658
• Sequence:
  MTSKLAVALLAAFLISAALCEGAVLPRSAKELRCQCIKTYSKPFHPKFIKELRVIESGPH
  CANTEIIVKLSDGRELCLDPKENWVQRVVEKFLKRAENS
• Function: IL-8 is a chemotactic factor that attracts neutrophils, basophils, and T-cells, but not monocytes. It is also involved in neutrophil activation. It is released from several cell types in response to an inflammatory stimulus. IL-8(6-77) has a 5-10-fold higher activity on neutrophil activation, IL-8(5-77) has increased activity on neutrophil activation and IL-8(7-77) has a higher affinity to receptors CXCR1 and CXCR2 as compared to IL-8(1-77), respectively.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Chemokine signaling pathway (hsa04062)
  NF-kappa B signaling pathway (hsa04064)
  Toll-like receptor signaling pathway (hsa04620)
  NOD-like receptor signaling pathway (hsa04621)
  RIG-I-like receptor signaling pathway (hsa04622)
  Non-alcoholic fatty liver disease (NAFLD) (hsa04932)
  Epithelial cell signaling in Helicobacter pylori infection (hsa05120)
  Shigellosis (hsa05131)
  Salmonella infection (hsa05132)
  Pertussis (hsa05133)
  Legionellosis (hsa05134)
  Chagas disease (American trypanosomiasis) (hsa05142)
  Malaria (hsa05144)
  Amoebiasis (hsa05146)
  Hepatitis C (hsa05160)
  Hepatitis B (hsa05161)
  Influenza A (hsa05164)
  Pathways in cancer (hsa05200)
  Transcriptional misregulation in cancer (hsa05202)
  Bladder cancer (hsa05219)
  Rheumatoid arthritis (hsa05323)
• Reactome Pathway:
  Peptide ligand-binding receptors (R-HSA-375276)
  Chemokine receptors bind chemokines (R-HSA-380108)
  ATF4 activates genes (R-HSA-380994)
  G alpha (i) signalling events (R-HSA-418594)
  Senescence-Associated Secretory Phenotype (SASP) (R-HSA-2559582)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ibuprofen	DM8VCBE	Dysmenorrhea	GA34.3	Approved	[1]

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ABX-IL8	DMCZFMS	Melanoma	2C30	Phase 2	[2]
BMS-986253	DM42B0C	Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[3]
MDX-018	DML5FX2	Autoimmune diabetes	5A10	Phase 1	[4]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
R-ketoprofen	DMHSUQ1	N. A.	N. A.	Discontinued in Phase 2	[1]

5 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-(2-(2,5-dichlorophenylamino)phenyl)acetic acid	DM54M6C	Discovery agent	N.A.	Investigative	[1]
2-(2-(2-chlorophenoxy)phenyl)acetic acid	DMBP1TQ	Discovery agent	N.A.	Investigative	[1]
2-(2-(2-chlorophenylamino)phenyl)acetic acid	DMPLV3A	Discovery agent	N.A.	Investigative	[1]
2-(2-(2-fluorophenoxy)phenyl)acetic acid	DMDSUR2	Discovery agent	N.A.	Investigative	[1]
2-(2-(2-fluorophenylamino)phenyl)acetic acid	DMVQ68F	Discovery agent	N.A.	Investigative	[1]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Melanoma	2C82	Skin	9.05E-17	2.09	3.08

References

• [1] Structure-Activity Relationship of novel phenylacetic CXCR1 inhibitors. Bioorg Med Chem Lett. 2009 Aug 1;19(15):4026-30.
• [2] Fully humanized neutralizing antibodies to interleukin-8 (ABX-IL8) inhibit angiogenesis, tumor growth, and metastasis of human melanoma. Am J Pathol. 2002 Jul;161(1):125-34.
• [3] Phase I trial of HuMax-IL8 (BMS-986253), an anti-IL-8 monoclonal antibody, in patients with metastatic or unresectable solid tumors. J Immunother Cancer. 2019 Sep 5;7(1):240.
• [4] Company report (Genmab)