Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTMWT8Z)

• DTT Name: C-X-C chemokine receptor type 1 (CXCR1)
• Synonyms: Interleukin-8 receptor A; IL8RA; IL-8R A; IL-8 receptor type 1; High affinity interleukin-8 receptor A; CXCR-1; CXC-R1; CMKAR1; CDw128a; CD181
• Gene Name: CXCR1
• DTT Type: Successful target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: CXCR1_HUMAN
• TTD ID: T00884
• Sequence:
  MSNITDPQMWDFDDLNFTGMPPADEDYSPCMLETETLNKYVVIIAYALVFLLSLLGNSLV
  MLVILYSRVGRSVTDVYLLNLALADLLFALTLPIWAASKVNGWIFGTFLCKVVSLLKEVN
  FYSGILLLACISVDRYLAIVHATRTLTQKRHLVKFVCLGCWGLSMNLSLPFFLFRQAYHP
  NNSSPVCYEVLGNDTAKWRMVLRILPHTFGFIVPLFVMLFCYGFTLRTLFKAHMGQKHRA
  MRVIFAVVLIFLLCWLPYNLVLLADTLMRTQVIQESCERRNNIGRALDATEILGFLHSCL
  NPIIYAFIGQNFRHGFLKILAMHGLVSKEFLARHRVTSYTSSSVNVSSNL
• Function: Binding of IL-8 to the receptor causes activation of neutrophils. This response is mediated via a G-protein that activate a phosphatidylinositol-calcium second messenger system. This receptor binds to IL-8 with a high affinity and to MGSA (GRO) with a low affinity. Receptor to interleukin-8, which is a powerful neutrophils chemotactic factor.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Chemokine signaling pathway (hsa04062)
  Endocytosis (hsa04144)
  Epithelial cell signaling in Helicobacter pylori infection (hsa05120)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Chemokine receptors bind chemokines (R-HSA-380108)

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
Reparixin	DMVBA7I	Pancreatic islet transplantation failure	NE84	Phase 3	[1]
SCH-527123	DMPUAOE	Chronic obstructive pulmonary disease	CA22	Phase 2	[2]
SX-682	DMHMG6X	Melanoma	2C30	Phase 1	[3]

2 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
INDOPROFEN	DM5QSKN	Gout	FA25	Withdrawn from market	[1]
R-ketoprofen	DMHSUQ1	N. A.	N. A.	Discontinued in Phase 2	[1]

12 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(R)-2-(4-Isobutyl-phenyl)-N-methoxy-propionamide	DMR8E0G	Discovery agent	N.A.	Investigative	[1]
(R)-2-(4-Isobutyl-phenyl)-propionamide	DMBQ0PR	Discovery agent	N.A.	Investigative	[1]
(R)-3-(4-Isobutyl-phenyl)-butan-2-one	DMQ2KF8	Discovery agent	N.A.	Investigative	[1]
(R)-N-Hydroxy-2-(4-isobutyl-phenyl)-propionamide	DMWRIQG	Discovery agent	N.A.	Investigative	[1]
1-(2-Bromo-phenyl)-3-(2,4-dihydroxy-phenyl)-urea	DMUSEOW	Discovery agent	N.A.	Investigative	[4]
1-(2-hydroxy-4-nitrophenyl)-3-phenylurea	DMN4G7U	Discovery agent	N.A.	Investigative	[5]
2-(3-Isobutyl-phenyl)-propionic acid	DM59VBG	Discovery agent	N.A.	Investigative	[1]
2-(3-Isopropyl-phenyl)-propionic acid	DMUOWNE	Discovery agent	N.A.	Investigative	[1]
2-[3-(1-Hydroxy-propyl)-phenyl]-propionic acid	DMDT9KG	Discovery agent	N.A.	Investigative	[1]
2-[3-(1-Phenyl-ethyl)-phenyl]-propionic acid	DMWIUR0	Discovery agent	N.A.	Investigative	[1]
2-[3-(2-Methyl-butyl)-phenyl]-propionic acid	DMKSDT4	Discovery agent	N.A.	Investigative	[1]
Il-8((3-73))K11R	DM10Z5W	Discovery agent	N.A.	Investigative	[6]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Chronic obstructive pulmonary disease	CA23	Lung tissue	1.29E-01	0.12	0.32
Chronic obstructive pulmonary disease	CA23	Small airway epithelium	1.66E-01	0.07	0.2

References

• [1] 2-Arylpropionic CXC chemokine receptor 1 (CXCR1) ligands as novel noncompetitive CXCL8 inhibitors. J Med Chem. 2005 Jun 30;48(13):4312-31.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] Inhibition of MDSC Trafficking with SX-682, a CXCR1/2 Inhibitor, Enhances NK-Cell Immunotherapy in Head and Neck Cancer Models. Clin Cancer Res. 2020 Mar 15;26(6):1420-1431.
• [4] Synthesis and structure-activity relationships of 3,5-diarylisoxazoles and 3,5-diaryl-1,2,4-oxadiazoles, novel classes of small molecule interleuki... Bioorg Med Chem Lett. 2004 Aug 16;14(16):4307-11.
• [5] Evaluation of potent and selective small-molecule antagonists for the CXCR2 chemokine receptor. J Med Chem. 2004 Mar 11;47(6):1319-21.
• [6] Il-8((3-73))K11R is a high affinity agonist of the neutrophil CXCR1 and CXCR2. Biochem Biophys Res Commun. 2001 Aug 24;286(3):595-600.