Target Information

Target General Infomation
Target ID
T56923
Former ID
TTDC00087
Target Name
High affinity interleukin-8 receptor B
Gene Name
CXCR2
Synonyms
CDw128b; CXCR-2; GRO/MGSA receptor; IL-8 receptor type 2; IL-8R B; Interleukin-8 receptor B; CXCR2
Target Type
Successful
Disease Asthma [ICD10: J45]
Chronic obstructive pulmonary disease [ICD9: 490-492, 494-496; ICD10: J40-J44, J47]
Cystic fibrosis; Chronic obstructive pulmonary disease [ICD9: 277.0, 490-492, 494-496; ICD10: E84, J40-J44, J47]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Fungal infections [ICD9: 110-118; ICD10: B35-B49]
Gout [ICD9: 274.00274.1274.8274.9; ICD10: M10]
Ischemia-reperfusion injury; Lung transplantation; Graft rejection in heart transplantation [ICD9: 996, 996.84; ICD10: T86, T86.81]
Function
Receptor for interleukin-8 which is a powerful neutrophil chemotactic factor. Binding of IL-8 to the receptor causes activation of neutrophils. This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. Binds to IL-8 with high affinity. Also binds with high affinity to CXCL3, GRO/MGSA and NAP-2.
BioChemical Class
GPCR rhodopsin
Target Validation
T56923
UniProt ID
P25025
Sequence
MEDFNMESDSFEDFWKGEDLSNYSYSSTLPPFLLDAAPCEPESLEINKYFVVIIYALVFL
LSLLGNSLVMLVILYSRVGRSVTDVYLLNLALADLLFALTLPIWAASKVNGWIFGTFLCK
VVSLLKEVNFYSGILLLACISVDRYLAIVHATRTLTQKRYLVKFICLSIWGLSLLLALPV
LLFRRTVYSSNVSPACYEDMGNNTANWRMLLRILPQSFGFIVPLLIMLFCYGFTLRTLFK
AHMGQKHRAMRVIFAVVLIFLLCWLPYNLVLLADTLMRTQVIQETCERRNHIDRALDATE
ILGILHSCLNPLIYAFIGQKFRHGLLKILAIHGLISKDSLPKDSRPSFVGSSSGHTSTTL
Drugs and Mode of Action
Drug(s) Clotrimazole Drug Info Approved Fungal infections [1], [2]
GSK1325756 Drug Info Phase 2 Chronic obstructive pulmonary disease [3], [4]
PS-938285 Drug Info Phase 2 Chronic obstructive pulmonary disease [5]
Reparixin Drug Info Phase 2 Ischemia-reperfusion injury; Lung transplantation; Graft rejection in heart transplantation [6], [7]
SB-265610 Drug Info Phase 2 Asthma [8]
SB-656933 Drug Info Phase 2 Cystic fibrosis; Chronic obstructive pulmonary disease [9], [10]
SCH-527123 Drug Info Phase 2 Chronic obstructive pulmonary disease [11], [12]
AZD-5122 Drug Info Phase 1 Chronic obstructive pulmonary disease [13]
AZD4721 Drug Info Phase 1 Chronic obstructive pulmonary disease [14]
INDOPROFEN Drug Info Withdrawn from market Gout [15]
R-KETOPROFEN Drug Info Discontinued in Phase 2 Discovery agent [16]
AZD-5069 Drug Info Discontinued in Phase 1 Chronic obstructive pulmonary disease [17]
SB-265610 Drug Info Discontinued in Phase 1 Chronic obstructive pulmonary disease [18]
SB-332235 Drug Info Discontinued in Phase 1 Chronic obstructive pulmonary disease [19]
Inhibitor (R)-2-(4-Isobutyl-phenyl)-N-methoxy-propionamide Drug Info [20]
(R)-2-(4-Isobutyl-phenyl)-propionamide Drug Info [20]
(R)-3-(4-Isobutyl-phenyl)-butan-2-one Drug Info [20]
(R)-N-Hydroxy-2-(4-isobutyl-phenyl)-propionamide Drug Info [20]
1-(2-bromophenyl)-3-(4-cyano-2-hydroxyphenyl)urea Drug Info [21]
1-(2-Hydroxy-3-nitro-phenyl)-3-phenyl-urea Drug Info [22]
1-(2-hydroxy-4-nitrophenyl)-3-phenylurea Drug Info [21]
1-(2-Hydroxy-5-nitro-phenyl)-3-phenyl-urea Drug Info [22]
1-(3-cyano-2-hydroxyphenyl)-3-phenylurea Drug Info [21]
1-(4-cyano-2-hydroxyphenyl)-3-phenylurea Drug Info [21]
1-(5-chloro-2-hydroxy-4-nitrophenyl)-3-phenylurea Drug Info [21]
2-(3-Isobutyl-phenyl)-propionic acid Drug Info [20]
2-(3-Isopropyl-phenyl)-propionic acid Drug Info [20]
2-[3-(1-Hydroxy-propyl)-phenyl]-propionic acid Drug Info [20]
2-[3-(1-Phenyl-ethyl)-phenyl]-propionic acid Drug Info [20]
2-[3-(2-Methyl-butyl)-phenyl]-propionic acid Drug Info [20]
5-(pentylthio)thiazolo[4,5-d]pyrimidin-7-ol Drug Info [23]
AZD-5069 Drug Info [24]
IBUPROPHEN Drug Info [20]
INDOPROFEN Drug Info [20]
R-KETOPROFEN Drug Info [20]
RAPARIXIN Drug Info [20]
Modulator AZD-5122 Drug Info [25]
Clotrimazole Drug Info
CXCR-2 targeting mabs Drug Info [26]
GSK1325756 Drug Info [27]
Reparixin Drug Info
SCH-527123 Drug Info
Antagonist AZD4721 Drug Info [28]
N-(3-(aminosulfonyl)-4-chloro-2-hydroxyphenyl)-N'-(2,3-dichlorophenyl) urea Drug Info [29]
PS-938285 Drug Info [30]
SB 225002 Drug Info [31]
SB 272844 Drug Info [32]
SB-265610 Drug Info [18]
SB-332235 Drug Info [18]
SB-656933 Drug Info [33]
SK&F 83589 Drug Info [34]
SX-517 Drug Info [35]
Agonist CXCL8 Drug Info [36]
Il-8((3-73))K11R Drug Info [37]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Cytokine-cytokine receptor interaction
Chemokine signaling pathway
Endocytosis
Epithelial cell signaling in Helicobacter pylori infection
NetPath Pathway TNFalpha Signaling Pathway
PANTHER Pathway Inflammation mediated by chemokine and cytokine signaling pathway
Interleukin signaling pathway
Pathway Interaction Database IL8- and CXCR2-mediated signaling events
Reactome Chemokine receptors bind chemokines
G alpha (i) signalling events
WikiPathways GPCRs, Class A Rhodopsin-like
Peptide GPCRs
GPCR ligand binding
GPCR downstream signaling
GPCRs, Other
References
REF 1Emerging drugs for chemotherapy-induced mucositis. Expert Opin Emerg Drugs. 2008 Sep;13(3):511-22.
REF 2(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2330).
REF 3ClinicalTrials.gov (NCT02469298) Safety, Tolerability and Clinical Effect of Danirixin in Adults With Influenza.
REF 4(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8500).
REF 5ClinicalTrials.gov (NCT01006161) Study of SCH 527123 in Subjects With Severe Asthma (Study P05109AM1). U.S. National Institutes of Health.
REF 6New developments in immunosuppressive therapy for heart transplantation. Expert Opin Emerg Drugs. 2009 Mar;14(1):1-21.
REF 7(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8498).
REF 8SB-656933, a novel CXCR2 selective antagonist, inhibits ex vivo neutrophil activation and ozone-induced airway inflammation in humans. Br J Clin Pharmacol. 2011 Aug;72(2):282-93.
REF 9(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8499).
REF 10Clinical pipeline report, company report or official report of GlaxoSmithKline.
REF 11Emerging drugs in chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2009 Mar;14(1):181-94.
REF 12(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8497).
REF 13ClinicalTrials.gov (NCT00984477) Study to Investigate the Activity of AZD5122 When Given as a Single Dose to Healthy Male Subjects. U.S. National Institutes of Health.
REF 14ClinicalTrials.gov (NCT01889160) Study to Investigate the Safety Profile of AZD4721 After Single Doses at Different Dose Levels. U.S. National Institutes of Health.
REF 15Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
REF 16Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007136)
REF 17Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800030696)
REF 18Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.
REF 19Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014165)
REF 20J Med Chem. 2005 Jun 30;48(13):4312-31.2-Arylpropionic CXC chemokine receptor 1 (CXCR1) ligands as novel noncompetitive CXCL8 inhibitors.
REF 21Bioorg Med Chem Lett. 2007 Mar 15;17(6):1713-7. Epub 2006 Dec 23.Comparison of N,N'-diarylsquaramides and N,N'-diarylureas as antagonists of the CXCR2 chemokine receptor.
REF 22J Med Chem. 2004 Mar 11;47(6):1319-21.Evaluation of potent and selective small-molecule antagonists for the CXCR2 chemokine receptor.
REF 23Bioorg Med Chem Lett. 2006 Feb 15;16(4):960-3. Epub 2005 Nov 15.Hit-to-Lead studies: the discovery of potent, orally bioavailable thiazolopyrimidine CXCR2 receptor antagonists.
REF 24Pharmacological characterization of AZD5069, a slowly reversible CXC chemokine receptor 2 antagonist. J Pharmacol Exp Ther. 2015 May;353(2):340-50.
REF 25Molecular Approaches To Target GPCRs in Cancer Therapy. Pharmaceuticals 2011, 4(4), 567-589.
REF 26(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 69).
REF 27Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
REF 28Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800038326)
REF 29A potent and selective nonpeptide antagonist of CXCR2 inhibits acute and chronic models of arthritis in the rabbit. J Immunol. 2002 Dec 1;169(11):6435-44.
REF 30CenterWatch. Drugs in Clinical Trials Database. CenterWatch. 2008.
REF 31Interleukin-8 receptor antagonists in pulmonary diseases. Curr Opin Pharmacol. 2001 Jun;1(3):242-7.
REF 32The selective CXCR2 antagonist SB272844 blocks interleukin-8 and growth-related oncogene-alpha-mediated inhibition of spontaneous neutrophil apoptosis. Pulm Pharmacol Ther. 2002;15(2):103-10.
REF 33Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
REF 34Identification of a potent, selective non-peptide CXCR2 antagonist that inhibits interleukin-8-induced neutrophil migration. J Biol Chem. 1998 Apr 24;273(17):10095-8.
REF 35Discovery of 2-[5-(4-Fluorophenylcarbamoyl)pyridin-2-ylsulfanylmethyl]phenylboronic Acid (SX-517): Noncompetitive Boronic Acid Antagonist of CXCR1 and CXCR2. J Med Chem. 2014 Oct 23;57(20):8378-97.
REF 36Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11791-6. Epub 2004 Jul 28.Noncompetitive allosteric inhibitors of the inflammatory chemokine receptors CXCR1 and CXCR2: prevention of reperfusion injury.
REF 37Il-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.

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