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

General Information of Drug (ID: DMP9TKE)

• Drug Name: PTC299 Drug Info
• Synonyms: 6-(4-Fluorophenyl)-2,3-dihydro-5-(4-pyridinyl)imidazo(2,1-b)thiazole; skf-86002; 72873-74-6; Skf 86002; F 86002; F 86002-A(2); UNII-9R6QDF1UO7; 9R6QDF1UO7; CHEMBL313417; 5-(4-Pyridyl)-6-(4-fluorophenyl)-2,3-dihydroimidazo(2,1-b)-thiazole; 4-[6-(4-fluorophenyl)-2H,3H-imidazo[2,1-b][1,3]thiazol-5-yl]pyridine; 6-(4-fluorophenyl)-5-(4-pyridyl)-2,3-dihydroimidazo[2,1-b]thiazole; 6-(4-Fluorophenyl)-2,3-dihydro-5-(4-pyridyl)imidazo[2,1-b]thiazole; Imidazo(2,1-b)thiazole,; SK&F 86002

Indication

Disease Entry	ICD 11	Status	REF
Rheumatoid arthritis	FA20	Phase 2	[1]
Solid tumour/cancer	2A00-2F9Z	Phase 2	[2]

• Therapeutic Class: Anticancer Agents
• Cross-matching ID:
  PubChem CID: 49787172
  TTD Drug ID: DMP9TKE

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 Vascular endothelial growth factor A (VEGFA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aflibercept	DMT3D5I	Central retinal vein occlusion with macular edema		Approved	[15]
Brolucizumab	DMW8QNG	Wet age-related macular degeneration	9B78.3Z	Approved	[16]
Faricimab	DM83SEB	Diabetic macular edema	9B71.02	Approved	[17]
Ranibizumab	DMSYPNW	Central retinal vein occlusion with macular edema		Approved	[18]
Bevacizumab	DMSD1UN	Adenocarcinoma	2D40	Approved	[19]
Avastin+/-Tarceva	DMA86FL	Non-small-cell lung cancer	2C25.Y	Phase 3	[20]
RG7221	DM8J9DC	Colorectal cancer	2B91.Z	Phase 2	[21]
RO5520985	DMD3WNP	Colorectal cancer	2B91.Z	Phase 2	[22]
Abicipar pegol	DM59OJ2	Diabetic macular edema	9B71.02	Phase 2	[23]
MP0250	DMR3VCY	Non-small-cell lung cancer	2C25.Y	Phase 1/2	[24]

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	[3]
Vascular endothelial growth factor A (VEGFA)	TTOHSBA	VEGFA_HUMAN	Modulator	[4]

References

• [1] 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: 6040).
• [2] ClinicalTrials.gov (NCT00911248) PTC299 for Treatment of Neurofibromatosis Type 2. U.S. National Institutes of Health.
• [3] Therapeutic intervention in a rat model of ARDS: I. Dual inhibition of arachidonic acid metabolism. Circ Shock. 1990 Nov;32(3):231-42.
• [4] Phase I and pharmacokinetic trial of PTC299 in pediatric patients with refractory or recurrent central nervous system tumors: a PBTC study.J Neurooncol.2015 Jan;121(1):217-24.
• [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] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [16] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [17] Faricimab: an investigational agent targeting the Tie-2/angiopoietin pathway and VEGF-A for the treatment of retinal diseases. Expert Opin Investig Drugs. 2021 Mar;30(3):193-200.
• [18] Development of ranibizumab, an anti-vascular endothelial growth factor antigen binding fragment, as therapy for neovascular age-related macular degeneration. Retina. 2006 Oct;26(8):859-70.
• [19] FDA Approved Drug Products from FDA Official Website. 2004. Application Number: (ANDA) 125085.
• [20] Clinical pipeline report, company report or official report of Genentech (2009).
• [21] Bispecific antibodies and their applications
• [22] Bispecific antibodies rise again. Nat Rev Drug Discov. 2014 Nov;13(11):799-801.
• [23] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [24] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)