Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMVBA7I)

• Drug Name: Reparixin Drug Info
• Synonyms: reparixin; repertaxin; 266359-83-5; UNII-U604E1NB3K; CHEMBL191413; U604E1NB3K; DF 1681Y; (R)-2-(4-isobutylphenyl)-N-(methylsulfonyl)propanamide; Reparixin [USAN:INN]; (2R)-2-[4-(2-methylpropyl)phenyl]-N-methylsulfonylpropanamide; (2R)-2-(4-(2-Methylpropyl)phenyl)-N-methylsulfonylpropanamide; 2-(4-isobutylphenyl)propionylmethanesulfonamide; Reparixin (USAN/INN); DSSTox_RID_81678; DSSTox_CID_26509; DSSTox_GSID_46509; ZINC8717; SCHEMBL1884299; GTPL8498; DTXSID6046509; EX-A2461; DF-1681Y; BCP10635; Tox21_112272; BDBM50169045; Repertaxin; Reparixin [INN]; Reparixin (INN/USAN); (R)-2-(4-isobutylphenyl)propionylmethanesulfonamide; RAPARIXIN

Indication

Disease Entry	ICD 11	Status	REF
Pancreatic islet transplantation failure	NE84	Phase 3	[1]
Graft rejection in heart transplantation	NE84	Phase 2	[2]
Ischemia-reperfusion injury	DB98.B	Phase 2	[2]
lung transplantation	PK80.20	Phase 2	[2]

• Cross-matching ID:
  PubChem CID: 9838712
  CAS Number: CAS 266359-83-5
  TTD Drug ID: DMVBA7I

Molecule-Related Drug Atlas

Drug(s) Targeting C-X-C chemokine receptor type 1 (CXCR1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ibuprofen	DM8VCBE	Dysmenorrhea	GA34.3	Approved	[3]
SCH-527123	DMPUAOE	Chronic obstructive pulmonary disease	CA22	Phase 2	[5]
SX-682	DMHMG6X	Melanoma	2C30	Phase 1	[6]
INDOPROFEN	DM5QSKN	Gout	FA25	Withdrawn from market	[3]
R-ketoprofen	DMHSUQ1	N. A.	N. A.	Discontinued in Phase 2	[3]
2-(3-Isopropyl-phenyl)-propionic acid	DMUOWNE	Discovery agent	N.A.	Investigative	[3]
2-[3-(1-Phenyl-ethyl)-phenyl]-propionic acid	DMWIUR0	Discovery agent	N.A.	Investigative	[3]
(R)-2-(4-Isobutyl-phenyl)-propionamide	DMBQ0PR	Discovery agent	N.A.	Investigative	[3]
(R)-N-Hydroxy-2-(4-isobutyl-phenyl)-propionamide	DMWRIQG	Discovery agent	N.A.	Investigative	[3]
2-[3-(2-Methyl-butyl)-phenyl]-propionic acid	DMKSDT4	Discovery agent	N.A.	Investigative	[3]

Drug(s) Targeting C-X-C chemokine receptor type 2 (CXCR2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ibuprofen	DM8VCBE	Dysmenorrhea	GA34.3	Approved	[3]
Clotrimazole	DMMFCIH	Cutaneous candidiasis	1F23.14	Approved	[7]
SCH-527123	DMPUAOE	Chronic obstructive pulmonary disease	CA22	Phase 2	[8]
SB-265610	DM8TKG5	Asthma	CA23	Phase 2	[9]
AZD-5069	DM3JSFK	Asthma	CA23	Phase 2	[10]
PS-938285	DMHZIFJ	Chronic obstructive pulmonary disease	CA22	Phase 2	[11]
GSK1325756	DMA6RBF	Chronic obstructive pulmonary disease	CA22	Phase 2	[12]
SB-656933	DMCY785	Chronic obstructive pulmonary disease	CA22	Phase 2	[13]
RIST4721	DMA3DKO	Hidradenitis suppurativa	ED92.0	Phase 2	[14]
SX-682	DMHMG6X	Melanoma	2C30	Phase 1	[6]

Drug(s) Affected By Interleukin-8 (CXCL8)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrocortisone	DMGEMB7	Acne vulgaris	ED80	Approved	[15]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[16]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[17]
Pantothenic acid	DM091H2	Vitamin deficiency	5B55-5B71	Approved	[18]
Mechlorethamine	DM0CVXA	Chronic myelogenous leukaemia	2A20.0	Approved	[19]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[20]
Fexofenadine	DM17ONX	Allergic rhinitis	CA08.0	Approved	[21]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[22]
Nitric Oxide	DM1RBYG	Hypertension	BA00-BA04	Approved	[23]
Lumiracoxib	DM1S4AG	Chronic renal failure	GB61.Z	Approved	[21]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
C-X-C chemokine receptor type 1 (CXCR1)	TTMWT8Z	CXCR1_HUMAN	Modulator	[3]
C-X-C chemokine receptor type 2 (CXCR2)	TT30C9G	CXCR2_HUMAN	Modulator	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Gene/Protein Processing	[4]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] URL: 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).
• [3] 2-Arylpropionic CXC chemokine receptor 1 (CXCR1) ligands as novel noncompetitive CXCL8 inhibitors. J Med Chem. 2005 Jun 30;48(13):4312-31.
• [4] Inhibition of interleukin-8 (CXCL8/IL-8) responses by repertaxin, a new inhibitor of the chemokine receptors CXCR1 and CXCR2. Biochem Pharmacol. 2005 Feb 1;69(3):385-94. doi: 10.1016/j.bcp.2004.10.007. Epub 2004 Dec 9.
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] 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.
• [7] Mode of action of clotrimazole: implications for therapy. Am J Obstet Gynecol. 1985 Aug 1;152(7 Pt 2):939-44.
• [8] CXCR2 Antagonist MK-7123.A Phase 2 Proof-of-Concept Trial for Chronic Obstructive Pulmonary Disease.Am J Respir Crit Care Med.2015 May 1;191(9):1001-11.
• [9] Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.
• [10] Pharmacological characterization of AZD5069, a slowly reversible CXC chemokine receptor 2 antagonist. J Pharmacol Exp Ther. 2015 May;353(2):340-50.
• [11] CenterWatch. Drugs in Clinical Trials Database. CenterWatch. 2008.
• [12] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [13] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [14] A Randomized, Double-Blind, Placebo-Controlled, Phase 2a Study to Evaluate the Efficacy and Safety of RIST4721 in Subjects with Palmoplantar Pustulosis. Dermatol Ther (Heidelb). 2021 Dec;11(6):2179-2193.
• [15] Monomeric and oligomeric flavanols maintain the endogenous glucocorticoid response in human macrophages in pro-oxidant conditions in vitro. Chem Biol Interact. 2018 Aug 1;291:237-244.
• [16] Nicotine up-regulates IL-8 expression in human gingival epithelial cells following stimulation with IL-1 or P. gingivalis lipopolysaccharide via nicotinic acetylcholine receptor signalling. Arch Oral Biol. 2012 May;57(5):483-90. doi: 10.1016/j.archoralbio.2011.10.007. Epub 2011 Nov 25.
• [17] Ca(2+) Signaling and IL-8 Secretion in Human Testicular Peritubular Cells Involve the Cation Channel TRPV2. Int J Mol Sci. 2018 Sep 19;19(9):2829. doi: 10.3390/ijms19092829.
• [18] Calcium pantothenate modulates gene expression in proliferating human dermal fibroblasts. Exp Dermatol. 2009 Nov;18(11):969-78. doi: 10.1111/j.1600-0625.2009.00884.x. Epub 2009 Apr 8.
• [19] Nitrogen mustard prevents transport of Fra-1 into the nucleus to promote c-Fos- and FosB-dependent IL-8 induction in injured mouse epidermis. Toxicol Lett. 2020 Feb 1;319:256-263. doi: 10.1016/j.toxlet.2019.10.006. Epub 2019 Oct 19.
• [20] ERE-independent ERalpha target genes differentially expressed in human breast tumors. Mol Cell Endocrinol. 2005 Dec 21;245(1-2):53-9. doi: 10.1016/j.mce.2005.10.003. Epub 2005 Nov 17.
• [21] An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
• [22] Gypenosides protect retinal pigment epithelium cells from oxidative stress. Food Chem Toxicol. 2018 Feb;112:76-85.
• [23] Nitric oxide synthase inhibitors attenuate ozone-induced airway inflammation in guinea pigs. Possible role of interleukin-8. Am J Respir Crit Care Med. 2000 Jan;161(1):249-56. doi: 10.1164/ajrccm.161.1.9804096.