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

General Information of Drug (ID: DMVS61L)

• Drug Name: Tepoxalin Drug Info
• Synonyms: TEPOXALIN; 103475-41-8; Orf-20485; ORF 20485; Tepoxaline; Tepoxalina; Tepoxalinum [Latin]; Tepoxaline [French]; Tepoxalina [Spanish]; RWJ 20485; Tepoxalin [USAN:INN]; 5-(4-Chlorophenyl)-N-hydroxy-1-(4-methoxyphenyl)-N-methyl-1H-pyrazole-3-propanamide; UNII-TZ4OX61974; C20H20ClN3O3; 1H-Pyrazole-3-propanamide, 5-(4-chlorophenyl)-N-hydroxy-1-(4-methoxyphenyl)-N-methyl-; CHEMBL316040; CHEBI:76277; TZ4OX61974; 5-(p-Chlorophenyl)-1-(p-methoxyphenyl)-N-methylpyrazole-3-propionohydroxamic acid; RWJ-20485; SIL-4R

Indication

Disease Entry	ICD 11	Status	REF
Asthma	CA23	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 59757
  ChEBI ID: CHEBI:76277
  CAS Number: CAS 103475-41-8
  TTD Drug ID: DMVS61L

Molecule-Related Drug Atlas

Drug(s) Targeting Arachidonate 5-lipoxygenase (5-LOX)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Zileuton	DMVRIC2	Allergic asthma	CA23.0	Approved	[5]
Diethylcarbamazine	DM1TJ8F	Elephantiasis		Approved	[6]
Silymarin	DMXBYQR	N. A.	N. A.	Phase 4	[7]
3,4-Dihydroxycinnamic Acid	DMVZL26	Thrombocytopenia	3B64	Phase 4	[8]
Avastin+/-Tarceva	DMA86FL	Non-small-cell lung cancer	2C25.Y	Phase 3	[9]
ABT-761	DM3FIC2	Asthma	CA23	Phase 3	[10]
Tenidap	DMHQRYE	Rheumatoid arthritis	FA20	Phase 3	[11]
FPL-62064	DMGF8MZ	Inflammation	1A00-CA43.1	Phase 3	[12]
Flobufen	DMPSG4D	Rheumatoid arthritis	FA20	Phase 3	[13]
Darbufelone	DMYVKM5	Asthma	CA23	Phase 2/3	[14]

Drug(s) Targeting Interleukin-4 (IL4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dexpramipexole	DM6KXAU	Eosinophilic asthma	CB02.0	Phase 3	[15]
SAR-156597	DMUICJD	Idiopathic pulmonary fibrosis	CB03.4	Phase 2	[16]
PEGylated pitrakinra	DMBPJ9U	Asthma	CA23	Phase 2	[17]
Romilkimab	DMYEZ5J	Idiopathic pulmonary fibrosis	CB03.4	Phase 2	[18]
IL-4R	DMYEGRH	N. A.	N. A.	Phase 2	[19]
Pascolizumab	DMU3XJP	Asthma	CA23	Phase 2	[17]
PF-07264660	DM0GI2H	Atopic dermatitis	EA80	Phase 1	[20]
PF-07275315	DMHRVUY	Atopic dermatitis	EA80	Phase 1	[20]

Drug(s) Affected By Polyunsaturated fatty acid 5-lipoxygenase (ALOX5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Meclofenamic acid	DM05FXR	Ankylosing spondylitis	FA92.0	Approved	[21]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[22]
SPI-1005	DM6XFHS	Reperfusion injury	ND56.Z	Approved	[23]
Fructose	DM43AN2	Vomiting	MD90	Approved	[24]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[25]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[26]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[27]
Loratadine	DMF3AN7	Allergy	4A80-4A85	Approved	[28]
Zoledronate	DMIXC7G	Adenocarcinoma	2D40	Approved	[29]
Niclosamide	DMJAGXQ	Cestodes infection	1F70-1F76	Approved	[30]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Arachidonate 5-lipoxygenase (5-LOX)	TT2J34L	LOX5_HUMAN	Inhibitor	[2]
Interleukin-4 (IL4)	TTLGTKB	IL4_HUMAN	Inhibitor	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Polyunsaturated fatty acid 5-lipoxygenase (ALOX5)	OT7FOIK2	LOX5_HUMAN	Gene/Protein Processing	[4]

References

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• [2] Preclinical toxicity evaluation of tepoxalin, a dual inhibitor of cyclooxygenase and 5-lipoxygenase, in Sprague-Dawley rats and beagle dogs. Fundam Appl Toxicol. 1996 Sep;33(1):38-48.
• [3] Therapeutic interference with interferon-gamma (IFN-gamma) and soluble IL-4 receptor (sIL-4R) in allergic diseases. Behring Inst Mitt. 1995 Jun;(96):118-30.
• [4] Toxicity of human monocytic THP-1 cells and microglia toward SH-SY5Y neuroblastoma cells is reduced by inhibitors of 5-lipoxygenase and its activating protein FLAP. J Leukoc Biol. 2003 Mar;73(3):369-78.
• [5] 5-lipoxygenase inhibitor zileuton attenuates ischemic brain damage: involvement of matrix metalloproteinase 9. Neurol Res. 2009 Oct;31(8):848-52.
• [6] Inhibition of leukotriene formation by diethylcarbamazine modifies the acid-base balance in the rabbits with blast injuries of the lungs. Vojnosanit Pregl. 1999 May-Jun;56(3):243-7.
• [7] Anti-inflammatory and anti-arthritic activities of silymarin acting through inhibition of 5-lipoxygenase. Phytomedicine. 2000 Mar;7(1):21-4.
• [8] Phenidone protects the nigral dopaminergic neurons from LPS-induced neurotoxicity. Neurosci Lett. 2008 Nov 7;445(1):1-6.
• [9] Simple analogues of anthralin: unusual specificity of structure and antiproliferative activity. J Med Chem. 1997 Nov 7;40(23):3773-80.
• [10] Treatment with 5-lipoxygenase inhibitor VIA-2291 (Atreleuton) in patients with recent acute coronary syndrome. Circ Cardiovasc Imaging. 2010 May;3(3):298-307.
• [11] The in vitro free radical scavenging activity of tenidap, a new dual cyclo-oxygenase and 5-1ipoxygenase inhibitor. Mediators Inflamm. 1992;1(2):141-3.
• [12] FPL 62064, a topically active 5-lipoxygenase/cyclooxygenase inhibitor. Agents Actions. 1990 Jun;30(3-4):432-42.
• [13] Pharmacological profile of the novel potent antirheumatic 4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid. Arzneimittelforschung. 1997 May;47(5):648-52.
• [14] Novel dual cyclooxygenase and lipoxygenase inhibitors targeting hyaluronan-CD44v6 pathway and inducing cytotoxicity in colon cancer cells. Bioorg Med Chem. 2013 May 1;21(9):2551-9.
• [15] Therapeutic strategies for eosinophilic dermatoses. Curr Opin Pharmacol. 2019 Jun;46:29-33.
• [16] Bispecific antibodies rise again. Nat Rev Drug Discov. 2014 Nov;13(11):799-801.
• [17] The potential of biologics for the treatment of asthma. Nat Rev Drug Discov. 2012 Dec;11(12):958-72.
• [18] A randomised, double-blind, placebo-controlled, 24-week, phase II, proof-of-concept study of romilkimab (SAR156597) in early diffuse cutaneous systemic sclerosis. Ann Rheum Dis. 2020 Dec;79(12):1600-1607.
• [19] Efficacy of soluble IL-4 receptor for the treatment of adults with asthma. J Allergy Clin Immunol. 2001 Jun;107(6):963-70.
• [20] Clinical pipeline report, company report or official report of Pfizer
• [21] Meclofenamate sodium is an inhibitor of both the 5-lipoxygenase and cyclooxygenase pathways of the arachidonic acid cascade in vitro. Prostaglandins Leukot Med. 1986 Aug;23(2-3):229-38.
• [22] Resveratrol prevents apoptosis in K562 cells by inhibiting lipoxygenase and cyclooxygenase activity. Eur J Biochem. 1999 Oct 1;265(1):27-34.
• [23] Molecular actions of ebselen--an antiinflammatory antioxidant. Gen Pharmacol. 1995 Oct;26(6):1153-69.
• [24] Non-nutritional sweeteners effects on endothelial vascular function. Toxicol In Vitro. 2020 Feb;62:104694. doi: 10.1016/j.tiv.2019.104694. Epub 2019 Oct 23.
• [25] Immediate up-regulation of the calcium-binding protein S100P and its involvement in the cytokinin-induced differentiation of human myeloid leukemia cells. Biochim Biophys Acta. 2005 Sep 10;1745(2):156-65.
• [26] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [27] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [28] Cetirizine and loratadine-based antihistamines with 5-lipoxygenase inhibitory activity. Bioorg Med Chem Lett. 2004 Nov 15;14(22):5591-4.
• [29] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [30] Mitochondrial uncoupling reveals a novel therapeutic opportunity for p53-defective cancers. Nat Commun. 2018 Sep 26;9(1):3931.