Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT8NGED)

• DTT Name: Prostaglandin G/H synthase 1 (COX-1)
• Synonyms: Prostaglandin-endoperoxide synthase 1; Prostaglandin H2 synthase 1; PHS 1; PGHS-1; PGH synthase 1; Cyclooxygenase-1; COX1; COX-1
• Gene Name: PTGS1
• DTT Type: Successful target; [1]
• Related Disease:
  Eye anterior segment structural developmental anomaly [ICD-11: LA11]
  Female pelvic pain [ICD-11: GA34]
  Hyper-lipoproteinaemia [ICD-11: 5C80]
  Indeterminate colitis [ICD-11: DD72]
  Nutritional deficiency [ICD-11: 5B50-5B71]
  Osteoarthritis [ICD-11: FA00-FA05]
  Pain [ICD-11: MG30-MG3Z]
  Postoperative inflammation [ICD-11: 1A00-CA43]
  Rheumatoid arthritis [ICD-11: FA20]
  Seborrhoeic dermatitis [ICD-11: EA81]
  Tuberculosis [ICD-11: 1B10-1B12]
  Ulcerative colitis [ICD-11: DD71]
• BioChemical Class: Paired donor oxygen oxidoreductase
• UniProt ID: PGH1_HUMAN
• TTD ID: T60529
• EC Number: EC 1.14.99.1
• Sequence:
  MSRSLLLWFLLFLLLLPPLPVLLADPGAPTPVNPCCYYPCQHQGICVRFGLDRYQCDCTR
  TGYSGPNCTIPGLWTWLRNSLRPSPSFTHFLLTHGRWFWEFVNATFIREMLMRLVLTVRS
  NLIPSPPTYNSAHDYISWESFSNVSYYTRILPSVPKDCPTPMGTKGKKQLPDAQLLARRF
  LLRRKFIPDPQGTNLMFAFFAQHFTHQFFKTSGKMGPGFTKALGHGVDLGHIYGDNLERQ
  YQLRLFKDGKLKYQVLDGEMYPPSVEEAPVLMHYPRGIPPQSQMAVGQEVFGLLPGLMLY
  ATLWLREHNRVCDLLKAEHPTWGDEQLFQTTRLILIGETIKIVIEEYVQQLSGYFLQLKF
  DPELLFGVQFQYRNRIAMEFNHLYHWHPLMPDSFKVGSQEYSYEQFLFNTSMLVDYGVEA
  LVDAFSRQIAGRIGGGRNMDHHILHVAVDVIRESREMRLQPFNEYRKRFGMKPYTSFQEL
  VGEKEMAAELEELYGDIDALEFYPGLLLEKCHPNSIFGESMIEIGAPFSLKGLLGNPICS
  PEYWKPSTFGGEVGFNIVKTATLKKLVCLNTKTCPYVSFRVPDASQDDGPAVERPSTEL
• Function: Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the generation of thromboxane A2 (TXA2), which promotes platelet activation and aggregation, vasoconstriction and proliferation of vascular smooth muscle cells.
• KEGG Pathway:
  Arachidonic acid metabolism (hsa00590)
  Metabolic pathways (hsa01100)
  Platelet activation (hsa04611)
  Serotonergic synapse (hsa04726)
• Reactome Pathway:
  Synthesis of Prostaglandins (PG) and Thromboxanes (TX) (R-HSA-2162123)
  COX reactions (R-HSA-140180)
• BioCyc Pathway: MetaCyc:HS01815-MON

Molecular Interaction Atlas (MIA) of This DTT

15 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aminosalicylic acid	DMENSL5	Inflammatory bowel disease	DD72	Approved	[2]
Balsalazide	DMO091F	Inflammatory bowel disease	DD72	Approved	[3]
Bromfenac	DMKB79O	Postoperative inflammation	1A00-CA43.1	Approved	[4]
Eicosapentaenoic acid/docosa-hexaenoic acid	DMMUCG4	Hypertriglyceridemia	5C80.1	Approved	[5]
Fenbufen	DMXGDFK	Arthritis	FA20	Approved	[6]
Flufenamic Acid	DMC8VNH	Dysmenorrhea	GA34.3	Approved	[7]
Gamma-homolinolenic acid	DMSXKYG	Malnutrition	5B50-5B71	Approved	[8], [9], [10]
Meclofenamate sodium	DMNL98G	Arthritis	FA20	Approved	[11]
Mesalazine	DMOL5IU	Ulcerative colitis	DD71	Approved	[1]
Naproxen	DMZ5RGV	Osteoarthritis	FA00-FA05	Approved	[12]
Piroxicam	DMTK234	Pain	MG30-MG3Z	Approved	[2]
Salicyclic acid	DM2F8XZ	Seborrhoeic dermatitis	EA81	Approved	[13]
Salsalate	DM13P4C	Rheumatoid arthritis	FA20	Approved	[14], [15]
Suprofen	DMKXJZ7	Miosis	LA11.62	Approved	[16]
Imrecoxib	DMVXLOD	N. A.	N. A.	Phase 4	[17]

6 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(S)-FLURBIPROFEN	DMF2O4T	Myalgia	FB56.2	Preregistration	[18]
Curcumin	DMQPH29	Solid tumour/cancer	2A00-2F9Z	Phase 3	[19]
Resveratrol	DM3RWXL	Giant cell arteritis	4A44.2	Phase 3	[20]
ThermoProfen	DMPGH7N	Pain	MG30-MG3Z	Phase 3	[21]
Epicatechin	DMN0EMP	Duchenne dystrophy	8C70	Phase 1/2	[22]
EXO-230	DM64PM7	Diabetic neuropathy	8C0Z	Phase 1/2	[23]

1 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Carbamate derivative 2	DMEWPQ6	N. A.	N. A.	Patented	[24]

8 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
INDOPROFEN	DM5QSKN	Gout	FA25	Withdrawn from market	[18]
Metamizole	DM79GRO	Fever	MG26	Withdrawn from market	[25]
Phenacetin	DMRQAM0	Analgesia	MB40.8	Withdrawn from market	[26]
CRx-401	DM39N7W	Type-2 diabetes	5A11	Discontinued in Phase 2	[27]
R-ketoprofen	DMHSUQ1	N. A.	N. A.	Discontinued in Phase 2	[18]
TEBUFELONE	DMMUE8P	Pain	MG30-MG3Z	Discontinued in Phase 2	[28]
ATLIPROFEN METHYL ESTER	DMS2FB3	Inflammation	1A00-CA43.1	Terminated	[2]
SC-58451	DMVGK24	N. A.	N. A.	Terminated	[29]

106 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(-)-3-O-acetylspectaline	DMKRTBM	Discovery agent	N.A.	Investigative	[30]
(11H-Dibenzo[b,e][1,4]dioxepin-2-yl)-acetic acid	DMSUPVE	Discovery agent	N.A.	Investigative	[31]
(11H-Dibenzo[b,e][1,4]dioxepin-7-yl)-acetic acid	DM5ZTXL	Discovery agent	N.A.	Investigative	[31]
(11H-Dibenzo[b,e][1,4]dioxepin-8-yl)-acetic acid	DMBY623	Discovery agent	N.A.	Investigative	[31]
(3-Chloro-4-Propoxy-Phenyl)-Acetic Acid	DMHODXG	Discovery agent	N.A.	Investigative	[32]
(R)-2-(4-Isobutyl-phenyl)-N-phenyl-propionamide	DMAD4JY	Discovery agent	N.A.	Investigative	[18]
(Z)-2'-des-methyl sulindac sulfide	DM0OEQJ	Discovery agent	N.A.	Investigative	[33]
1,2-dihydro-3-(2,3,4-trimethoxyphenyl)naphthalene	DMST60D	Discovery agent	N.A.	Investigative	[34]
1-(4-(methylsulfonyl)phenyl)-3-p-tolylurea	DMMSQLC	Discovery agent	N.A.	Investigative	[35]
1-(4-(methylsulfonyl)phenyl)-3-phenylurea	DMH7RY0	Discovery agent	N.A.	Investigative	[35]
1-(4-aminosulfonylphenyl)-2-(2-pyridyl)acetylene	DMWA6G1	Discovery agent	N.A.	Investigative	[36]
1-(4-aminosulfonylphenyl)-2-(4-pyridyl)acetylene	DMP93E2	Discovery agent	N.A.	Investigative	[36]
2'-epi-guianin	DMNVJY0	Discovery agent	N.A.	Investigative	[37]
2,4'-Dimethoxy-5,3'-di-(2-propenyl)-biphenyl	DMWNJ84	Discovery agent	N.A.	Investigative	[38]
2-(1,1'-Biphenyl-4-Yl)Propanoic Acid	DMUE0D6	Discovery agent	N.A.	Investigative	[32], [39]
2-(2,3,4-trimethoxyphenyl)-1H-indene	DMFU1PK	Discovery agent	N.A.	Investigative	[34]
2-(2-(2,6-dimethylphenylamino)phenyl)acetic acid	DMJ2DE4	Discovery agent	N.A.	Investigative	[40]
2-(2-methoxyphenyl)-1H-indene	DMXFYN8	Discovery agent	N.A.	Investigative	[34]
2-(2-Methylpropanoyl)-1,3,5-benzenetriol	DMPH63G	Discovery agent	N.A.	Investigative	[41]
2-(3'-Allyl-biphenyl-4-yl)-propionic acid	DMAGFUH	Discovery agent	N.A.	Investigative	[42]
2-(3'-Ethyl-biphenyl-4-yl)-propionic acid	DMPLN58	Discovery agent	N.A.	Investigative	[42]
2-(3'-Ethylsulfanyl-biphenyl-4-yl)-propionic acid	DMPGYDA	Discovery agent	N.A.	Investigative	[42]
2-(3'-Vinyl-biphenyl-4-yl)-propionic acid	DM7NGV1	Discovery agent	N.A.	Investigative	[42]
2-(3-Phenyl-propyl)-1,2-dihydro-indazol-3-one	DMIQBXD	Discovery agent	N.A.	Investigative	[43]
2-(N-(2-Ffuorophenyl)pyrrol-3-yl) acetic acid	DMRNOM6	Discovery agent	N.A.	Investigative	[44]
2-(N-(2-fluorophenyl)pyrrol-2-yl) acetic acid	DMCL9E6	Discovery agent	N.A.	Investigative	[44]
2-(p-Methylsulfonylbenzoyl)furan	DMLT635	Discovery agent	N.A.	Investigative	[45]
2-Benzyl-1,2-dihydro-indazol-3-one	DM1CB5J	Discovery agent	N.A.	Investigative	[43]
2-Bromoacetyl Group	DMIHJSA	Discovery agent	N.A.	Investigative	[46]
2-Furan-2-ylmethyl-1,2-dihydro-indazol-3-one	DMQIRY7	Discovery agent	N.A.	Investigative	[43]
2-Methyl-1,2-dihydro-indazol-3-one	DMDJHFQ	Discovery agent	N.A.	Investigative	[43]
2-Naphthalen-2-ylmethyl-1,2-dihydro-indazol-3-one	DM1EJ6W	Discovery agent	N.A.	Investigative	[43]
2-Phenethyl-1,2-dihydro-indazol-3-one	DM0WMBC	Discovery agent	N.A.	Investigative	[43]
2-Phenyl-1,2-dihydro-indazol-3-one	DM28CLZ	Discovery agent	N.A.	Investigative	[43]
2-[4-(1H-Indol-5-yl)-phenyl]-propionic acid	DMUHECR	Discovery agent	N.A.	Investigative	[42]
3 beta-O-acetyloleanolic acid	DM1L5IJ	Discovery agent	N.A.	Investigative	[47]
3-(4-Methanesulfonyl-phenyl)-1-phenyl-propynone	DMSR2O3	Discovery agent	N.A.	Investigative	[48]
4'-Methoxy-5,3'-dipropyl-biphenyl-2ol	DM5FRV2	Discovery agent	N.A.	Investigative	[38]
4,5-Bis(4-chlorophenyl)-1,2-selenazole	DMIO254	Discovery agent	N.A.	Investigative	[49]
4,5-Bis(4-chlorophenyl)isothiazole	DMENLFY	Discovery agent	N.A.	Investigative	[50]
4,5-Bis(4-methoxyphenyl)-1,2-selenazole	DMKHD1M	Discovery agent	N.A.	Investigative	[49]
4,5-Bis(4-methoxyphenyl)-3H-1,2-dithiol-3-one	DMI39QT	Discovery agent	N.A.	Investigative	[50]
4,5-Bis(4-methoxyphenyl)-3H-1,2-dithiole-3-thione	DMPW145	Discovery agent	N.A.	Investigative	[50]
4,5-Bis(4-methoxyphenyl)isothiazole	DM90DV6	Discovery agent	N.A.	Investigative	[50]
4-(4-Chlorophenyl)-5-(4-methoxyphenyl)isothiazole	DMODVGN	Discovery agent	N.A.	Investigative	[50]
4-(4-Chlorophenyl)-5-p-tolyl-1,2-selenazole	DMZBEYO	Discovery agent	N.A.	Investigative	[49]
4-(4-Chlorophenyl)-5-p-tolyl-3H-1,2-dithiol-3-one	DMVDF9Q	Discovery agent	N.A.	Investigative	[50]
4-(4-Chlorophenyl)-5-p-tolylisothiazole	DMMK9RC	Discovery agent	N.A.	Investigative	[50]
4-(5-(4-Hydroxyphenyl)isothiazol-4-yl)phenol	DMK1ZF2	Discovery agent	N.A.	Investigative	[50]
4-amino-N-(2-chlorophenyl)benzenesulfonamide	DM6PQ5V	Discovery agent	N.A.	Investigative	[51]
4-amino-N-(4-chlorophenyl)benzenesulfonamide	DMCUSD4	Discovery agent	N.A.	Investigative	[51]
4-amino-N-p-tolylbenzenesulfonamide	DMLW651	Discovery agent	N.A.	Investigative	[51]
5,3'-Dipropyl-biphenyl-2,4'-diol	DMJRXLD	Discovery agent	N.A.	Investigative	[38]
5-(2-1H-indenyl)-1,3-benzodioxole	DM149IX	Discovery agent	N.A.	Investigative	[34]
5-(2-Imidazol-1-yl-ethyl)-7,8-dihydro-quinoline	DMCP5U8	Discovery agent	N.A.	Investigative	[52]
5-(4-Chlorophenyl)-4-(4-methoxyphenyl)isothiazole	DMSTG03	Discovery agent	N.A.	Investigative	[50]
5-(4-Chlorophenyl)-4-p-tolyl-1,2-selenazole	DMY0P86	Discovery agent	N.A.	Investigative	[49]
5-(4-Chlorophenyl)-4-p-tolyl-3H-1,2-dithiol-3-one	DMFYEL8	Discovery agent	N.A.	Investigative	[50]
5-(4-Chlorophenyl)-4-p-tolylisothiazole	DMA1N75	Discovery agent	N.A.	Investigative	[50]
5-(4-Methoxyphenyl)-4-p-tolyl-1,2-selenazole	DMEV8WS	Discovery agent	N.A.	Investigative	[49]
5-(4-Methoxyphenyl)-4-p-tolylisothiazole	DMJSTCK	Discovery agent	N.A.	Investigative	[50]
5-Ethyl-3,4-diphenyl-isoxazole	DMRIGXA	Discovery agent	N.A.	Investigative	[53]
5-Methyl-3,4-diphenyl-isoxazole	DM0G2N5	Discovery agent	N.A.	Investigative	[53]
5-Phenyl-pentanoic acid benzyl-hydroxy-amide	DM3B6A8	Discovery agent	N.A.	Investigative	[54]
Acetic acid 2-hept-2-ynylsulfanyl-phenyl ester	DM97DJL	Discovery agent	N.A.	Investigative	[55]
Acetic acid 2-hept-3-ynylsulfanyl-phenyl ester	DMD89A1	Discovery agent	N.A.	Investigative	[55]
Acetic acid 2-heptylselanyl-phenyl ester	DM50BTA	Discovery agent	N.A.	Investigative	[55]
Acetic acid 2-heptylsulfanyl-phenyl ester	DMLPRIG	Discovery agent	N.A.	Investigative	[55]
Acetic acid 2-hex-2-ynylsulfanyl-phenyl ester	DMFQE1C	Discovery agent	N.A.	Investigative	[55]
Acetic acid 2-hexylsulfanyl-phenyl ester	DMAKNUH	Discovery agent	N.A.	Investigative	[55]
Acetic acid 2-pentylsulfanyl-phenyl ester	DMFKRIH	Discovery agent	N.A.	Investigative	[55]
Acetic Acid Salicyloyl-Amino-Ester	DMLTNHY	Discovery agent	N.A.	Investigative	[32]
Alpha-D-Mannose	DMF5DLW	Discovery agent	N.A.	Investigative	[46]
Arachidonic acid	DMUOQZD	Discovery agent	N.A.	Investigative	[46]
B-Octylglucoside	DMMO75G	Discovery agent	N.A.	Investigative	[46]
Beta-D-Glucose	DM5IHYP	Discovery agent	N.A.	Investigative	[46]
Beta-D-Mannose	DMHIG9K	Discovery agent	N.A.	Investigative	[46]
CATECHIN	DMY38SB	Discovery agent	N.A.	Investigative	[22]
DEMETHOXYCURCUMIN	DMO5UGV	Discovery agent	N.A.	Investigative	[19]
FR122047	DMAYTWN	Discovery agent	N.A.	Investigative	[56]
Heme	DMGC287	Discovery agent	N.A.	Investigative	[32]
HONOKIOL	DMJWT3X	Discovery agent	N.A.	Investigative	[38]
Hyperforin	DM2L3PE	Discovery agent	N.A.	Investigative	[57]
IODOINDOMETHACIN	DM3BL0G	Discovery agent	N.A.	Investigative	[39]
IODOSUPROFEN	DMOE8LT	Discovery agent	N.A.	Investigative	[39]
METHYLHONOKIOL	DM9YE6K	Discovery agent	N.A.	Investigative	[38]
N-(1H-indazol-5-yl)acetamide	DMIMJNU	Discovery agent	N.A.	Investigative	[58]
N-(3-(phenylthio)pyridin-4-yl)methanesulfonamide	DMSJX1H	Discovery agent	N.A.	Investigative	[59]
N-(3-phenoxy-4-pyridinyl)ethanesulfonamide	DMXF46V	Discovery agent	N.A.	Investigative	[60]
N-(3-phenoxy-4-pyridinyl)propanesulfonamide	DMN1DPJ	Discovery agent	N.A.	Investigative	[60]
N-(3-phenoxypyridin-4-yl)methanesulfonamide	DM7CM3F	Discovery agent	N.A.	Investigative	[59]
N-(3-phenylamino-4-pyridinyl)methanesulfonamide	DMJB7SE	Discovery agent	N.A.	Investigative	[59]
Nitroflurbiprofen	DMWCV48	Discovery agent	N.A.	Investigative	[61], [62], [63]
O-Acetylserine	DMAEHFT	Discovery agent	N.A.	Investigative	[46]
Oxametacin	DMWVLG1	Discovery agent	N.A.	Investigative	[64]
P-(2'-Iodo-5'-Thenoyl)Hydrotropic Acid	DMJ0W43	Discovery agent	N.A.	Investigative	[32]
Phenazone	DMCE985	Discovery agent	N.A.	Investigative	[65]
PHENIDONE	DMJD8XN	Discovery agent	N.A.	Investigative	[43]
Prifelone	DMLI4RF	Discovery agent	N.A.	Investigative	[66]
Primary alcohol metabolite of celecoxib	DMA8GI6	Discovery agent	N.A.	Investigative	[67]
Protoporphyrin Ix Containing Co	DMJ8TP3	Discovery agent	N.A.	Investigative	[46]
Resorcinol	DMM37C0	Discovery agent	N.A.	Investigative	[22]
Resveratrol Potassium3-Sulfate	DMN1RLA	Discovery agent	N.A.	Investigative	[68]
Resveratrol Potassium4,-Sulfate	DMMFP57	Discovery agent	N.A.	Investigative	[68]
SC-560	DMT1GJL	Discovery agent	N.A.	Investigative	[69]
TRL-382	DMU3E1M	Neuropathic pain	8E43.0	Investigative	[70]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Alzheimer's disease	8A00.0	Entorhinal cortex	3.97E-03	0.16	0.43
Atopic dermatitis	EA90	Skin	4.11E-05	-0.37	-1.66
Rectal cancer	2C82	Rectal colon tissue	4.06E-03	-0.9	-2.26
Type 2 diabetes	5A11	Liver tissue	3.77E-01	0.32	0.73
Rheumatoid arthritis	FA20	Synovial tissue	7.25E-01	-0.04	-0.06
Osteoarthritis	FA20	Synovial tissue	7.89E-01	0.02	0.02
Asthma	CA23	Nasal and bronchial airway	5.11E-09	0.51	0.96

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: Prostaglandin G/H synthase 1 (COX-1) DME Info
• Gene Name: PTGS1

30 Approved Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Candesartan	DMRK8OT	Hypertension	BA00-BA04	Approved	[71]
Dapsone	DM4LT8A	Pneumocystis pneumonia	CA40.20	Approved	[71]
Diazepam	DM08E9O	Epilepsy	8A60-8A68	Approved	[71]
Diphenhydramine	DMKQTBA	Meniere disease	AB31.0	Approved	[71]
Eicosapentaenoic acid/docosa-hexaenoic acid	DMMUCG4	Hypertriglyceridemia	5C80.1	Approved	[72]
Eletriptan	DMW649X	Migraine	8A80	Approved	[71]
Etoposide	DMNH3PG	Solid tumour/cancer	2A00-2F9Z	Approved	[73]
Gamma-homolinolenic acid	DMSXKYG	Malnutrition	5B50-5B71	Approved	[72]
Gamolenic acid	DMQN30Z	Allergy	4A80-4A85	Approved	[72]
Hexobarbital	DMQ314B	Anaesthesia	9A78.6	Approved	[71]
Ifosfamide	DMCT3I8	Solid tumour/cancer	2A00-2F9Z	Approved	[71]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[71]
Irbesartan	DMTP1DC	Hypertension	BA00-BA04	Approved	[71]
Ketobemidone	DMM3L6Z	Pain	MG30-MG3Z	Approved	[71]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[71]
Nateglinide	DMLK2QH	Diabetic complication	5A2Y	Approved	[71]
Nortriptyline	DM4KDYJ	Depression	6A70-6A7Z	Approved	[71]
Pioglitazone	DMKJ485	Diabetic complication	5A2Y	Approved	[71]
Rofecoxib	DM3P5DA	Osteoarthritis	FA00-FA05	Approved	[71]
Rosiglitazone	DMY6EAO	Type-2 diabetes	5A11	Approved	[71]
Sulfamethoxazole	DMB08GE	Bacterial infection	1A00-1C4Z	Approved	[71]
Terbinafine	DMI6HUW	Fungal infection	1F29-1F2F	Approved	[71]
Thalidomide	DM70BU5	Multiple myeloma	2A83	Approved	[71]
Trabectedin	DMG3Y89	Solid tumour/cancer	2A00-2F9Z	Approved	[71]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[71]
Voriconazole	DMAOL2S	Invasive aspergillosis	1F20.0	Approved	[71]
Zafirlukast	DMHNQOG	Asthma	CA23	Approved	[71]
Zileuton	DMVRIC2	Asthma	CA23	Approved	[71]
Zopiclone	DMPI6Z0	Insomnia	7A00-7A0Z	Approved	[71]
Zaltoprofen	DM9RJH7	Anaesthesia	9A78.6	Phase 4	[71]

1 Discontinued Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Seratrodast	DMPNTDL	Allergic asthma	CA23.0	Discontinued in Phase 3	[71]

5 Investigative Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Alpha-linolenic acid	DMY64HE	Discovery agent	N.A.	Investigative	[72]
Arachidonic acid	DMUOQZD	Discovery agent	N.A.	Investigative	[74]
BML3-C01	DMER2WS	Discovery agent	N.A.	Investigative	[72]
Eicosadienoic acid	DMVJK9W	Discovery agent	N.A.	Investigative	[72]
Icosapentum	DMF1CM7	Discovery agent	N.A.	Investigative	[72]

References

• [1] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [3] Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34.
• [4] Comparison of cyclooxygenase inhibitory activity and ocular anti-inflammatory effects of ketorolac tromethamine and bromfenac sodium. Curr Med Res Opin. 2006 Jun;22(6):1133-40.
• [5] Cox-2 inhibitory effects of naturally occurring and modified fatty acids. J Nat Prod. 2001 Jun;64(6):745-9.
• [6] Fenbufen based 3-[5-(substituted aryl)-1,3,4-oxadiazol-2-yl]-1-(biphenyl-4-yl)propan-1-ones as safer antiinflammatory and analgesic agents. Eur J Med Chem. 2009 Sep;44(9):3798-804.
• [7] Ouellet M, Percival MD: Effect of inhibitor time-dependency on selectivity towards cyclooxygenase isoforms. Biochem J. 1995 Feb 15;306 ( Pt 1):247-51.
• [8] Differential metabolism of dihomo-gamma-linolenic acid and arachidonic acid by cyclo-oxygenase-1 and cyclo-oxygenase-2: implications for cellular synthesis of prostaglandin E1 and prostaglandin E2. Biochem J. 2002 Jul 15;365(Pt 2):489-96.
• [9] Structure of eicosapentaenoic and linoleic acids in the cyclooxygenase site of prostaglandin endoperoxide H synthase-1. J Biol Chem. 2001 Oct 5;276(40):37547-55.
• [10] Mutational and X-ray crystallographic analysis of the interaction of dihomo-gamma -linolenic acid with prostaglandin endoperoxide H synthases. J Biol Chem. 2001 Mar 30;276(13):10358-65.
• [11] Role of COX-2-derived metabolites in regulation of the renal hemodynamic response to norepinephrine. Am J Physiol Renal Physiol. 2001 Nov;281(5):F975-82.
• [12] Comparative inhibitory activity of rofecoxib, meloxicam, diclofenac, ibuprofen, and naproxen on COX-2 versus COX-1 in healthy volunteers. J Clin Pharmacol. 2000 Oct;40(10):1109-20.
• [13] The C50T polymorphism of the cyclooxygenase-1 gene and the risk of thrombotic events during low-dose therapy with acetyl salicylic acid. Thromb Haemost. 2008 Jul;100(1):70-5.
• [14] New non-steroidal anti-rheumatic drugs: selective inhibitors of inducible cyclooxygenase. Med Klin (Munich). 1998 Jul 15;93(7):407-15.
• [15] Aspirin and NSAID sensitivity. Immunol Allergy Clin North Am. 2004 Aug;24(3):491-505, vii.
• [16] Differential binding mode of diverse cyclooxygenase inhibitors. J Mol Graph Model. 2002 Mar;20(5):359-71.
• [17] Synthesis and anti-inflammatory activity of the major metabolites of imrecoxib. Bioorg Med Chem Lett. 2009 Apr 15;19(8):2270-2.
• [18] 2-Arylpropionic CXC chemokine receptor 1 (CXCR1) ligands as novel noncompetitive CXCL8 inhibitors. J Med Chem. 2005 Jun 30;48(13):4312-31.
• [19] Design, synthesis, biological evaluation and molecular docking of curcumin analogues as antioxidant, cyclooxygenase inhibitory and anti-inflammator... Bioorg Med Chem Lett. 2005 Apr 1;15(7):1793-7.
• [20] Resveratrol is a peroxidase-mediated inactivator of COX-1 but not COX-2: a mechanistic approach to the design of COX-1 selective agents. J Biol Chem. 2004 May 21;279(21):22727-37.
• [21] Topical NSAID therapy for musculoskeletal pain. Pain Med. 2010 Apr;11(4):535-49.
• [22] Mechanism-based inactivation of COX-1 by red wine m-hydroquinones: a structure-activity relationship study. J Nat Prod. 2004 Nov;67(11):1777-82.
• [23] Inhibiting Amadori-modified albumin formation improves biomarkers of podocyte damage in diabetic rats. Physiol Rep. 2013 September; 1(4): e00083.
• [24] Fatty acid amide hydrolase inhibitors: a patent review (2009-2014).Expert Opin Ther Pat. 2015;25(11):1247-66.
• [25] Mechanisms of action of paracetamol and related analgesics. Inflammopharmacology. 2003;11(4):401-13.
• [26] Direct toxicity of nonsteroidal antiinflammatory drugs for renal medullary cells. Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5317-22.
• [27] ClinicalTrials.gov (NCT00506298) Study of CRx-401 on Glucose Levels in Subjects With Type II Diabetes. U.S. National Institutes of Health.
• [28] New cyclooxygenase-2/5-lipoxygenase inhibitors. 2. 7-tert-butyl-2,3-dihydro-3,3-dimethylbenzofuran derivatives as gastrointestinal safe antiinflamm... J Med Chem. 1998 Mar 26;41(7):1124-37.
• [29] Novel 1,2-diarylcyclobutenes: Selective and orally active cox-2 inhibitors, Bioorg. Med. Chem. Lett. 6(22):2677-2682 (1996).
• [30] Lipoperoxidation and cyclooxygenase enzyme inhibitory piperidine alkaloids from Cassia spectabilis green fruits. J Nat Prod. 2007 Dec;70(12):2026-8.
• [31] Synthesis and antiinflammatory/analgesic activities of 11H-dibenzo[b, e,][1,4]dioxepinacetic acids. J Med Chem. 1986 Aug;29(8):1436-41.
• [32] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [33] The influence of double bond geometry in the inhibition of cyclooxygenases by sulindac derivatives. Bioorg Med Chem Lett. 2009 Jun 15;19(12):3271-4.
• [34] 'Bridged' stilbene derivatives as selective cyclooxygenase-1 inhibitors. Bioorg Med Chem. 2007 Sep 15;15(18):6109-18.
• [35] Design and synthesis of 1,3-diarylurea derivatives as selective cyclooxygenase (COX-2) inhibitors. Bioorg Med Chem Lett. 2008 Feb 15;18(4):1336-9.
• [36] Synthesis and cyclooxygenase inhibitory activities of linear 1-(methanesulfonylphenyl or benzenesulfonamido)-2-(pyridyl)acetylene regioisomers. Bioorg Med Chem. 2008 Feb 15;16(4):1948-56.
• [37] COX, LOX and platelet aggregation inhibitory properties of Lauraceae neolignans. Bioorg Med Chem Lett. 2009 Dec 15;19(24):6922-5.
• [38] Design and synthesis of ten biphenyl-neolignan derivatives and their in vitro inhibitory potency against cyclooxygenase-1/2 activity and 5-lipoxyge... Bioorg Med Chem. 2009 Jul 1;17(13):4459-65.
• [39] In silico search for multi-target anti-inflammatories in Chinese herbs and formulas. Bioorg Med Chem. 2010 Mar 15;18(6):2204-2218.
• [40] Molecular determinants for the selective inhibition of cyclooxygenase-2 by lumiracoxib. J Biol Chem. 2007 Jun 1;282(22):16379-90.
• [41] Anti-inflammatory acylphloroglucinol derivatives from Hops (Humulus lupulus). J Nat Prod. 2005 Oct;68(10):1545-8.
• [42] Structure-based design of COX-2 selectivity into flurbiprofen. Bioorg Med Chem Lett. 1999 Feb 8;9(3):307-12.
• [43] Indazolinones, a new series of redox-active 5-lipoxygenase inhibitors with built-in selectivity and oral activity. J Med Chem. 1991 Mar;34(3):1028-36.
• [44] Synthesis and biological activity of new anti-inflammatory compounds containing the 1,4-benzodioxine and/or pyrrole system. Bioorg Med Chem. 2007 Jul 15;15(14):4876-90.
• [45] Synthesis, anti-inflammatory activity, and in vitro antitumor effect of a novel class of cyclooxygenase inhibitors: 4-(aryloyl)phenyl methyl sulfones. J Med Chem. 2010 Sep 23;53(18):6560-71.
• [46] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [47] Nitrogen-containing phorbol esters from Croton ciliatoglandulifer and their effects on cyclooxygenases-1 and -2. J Nat Prod. 2006 Jun;69(6):887-90.
• [48] Synthesis and biological evaluation of 1,3-diphenylprop-2-yn-1-ones as dual inhibitors of cyclooxygenases and lipoxygenases. Bioorg Med Chem Lett. 2005 Nov 1;15(21):4842-5.
• [49] Investigations concerning the COX/5-LOX inhibiting and hydroxyl radical scavenging potencies of novel 4,5-diaryl isoselenazoles. Eur J Med Chem. 2008 Jun;43(6):1152-9.
• [50] Diaryl-dithiolanes and -isothiazoles: COX-1/COX-2 and 5-LOX-inhibitory, *OH scavenging and anti-adhesive activities. Bioorg Med Chem. 2009 Jan 15;17(2):558-68.
• [51] Analgesic agents without gastric damage: design and synthesis of structurally simple benzenesulfonanilide-type cyclooxygenase-1-selective inhibitors. Bioorg Med Chem. 2007 Jan 15;15(2):1014-21.
• [52] 1-imidazolyl(alkyl)-substituted di- and tetrahydroquinolines and analogues: syntheses and evaluation of dual inhibitors of thromboxane A(2) synthas... J Med Chem. 2000 May 4;43(9):1841-51.
• [53] Novel synthesis of 3,4-diarylisoxazole analogues of valdecoxib: reversal cyclooxygenase-2 selectivity by sulfonamide group removal. J Med Chem. 2004 Sep 23;47(20):4881-90.
• [54] Differential effects of a series of hydroxamic acid derivatives on 5-lipoxygenase and cyclooxygenase from neutrophils and 12-lipoxygenase from plat... J Med Chem. 1989 Aug;32(8):1836-42.
• [55] Covalent modification of cyclooxygenase-2 (COX-2) by 2-acetoxyphenyl alkyl sulfides, a new class of selective COX-2 inactivators. J Med Chem. 1998 Nov 19;41(24):4800-18.
• [56] The analgesic effect profile of FR122047, a selective cyclooxygenase-1 inhibitor, in chemical nociceptive models. Eur J Pharmacol. 2000 Mar 10;391(1-2):49-54.
• [57] Hyperforin is a dual inhibitor of cyclooxygenase-1 and 5-lipoxygenase. Biochem Pharmacol. 2002 Dec 15;64(12):1767-75.
• [58] New analgesics synthetically derived from the paracetamol metabolite N-(4-hydroxyphenyl)-(5Z,8Z,11Z,14Z)-icosatetra-5,8,11,14-enamide. J Med Chem. 2008 Dec 25;51(24):7800-5.
• [59] Pyridine analogues of nimesulide: design, synthesis, and in vitro and in vivo pharmacological evaluation as promising cyclooxygenase 1 and 2 inhibi... J Med Chem. 2009 Oct 8;52(19):5864-71.
• [60] Design, synthesis, and pharmacological evaluation of pyridinic analogues of nimesulide as cyclooxygenase-2 selective inhibitors. J Med Chem. 2004 Dec 30;47(27):6749-59.
• [61] The cyclooxygenase inhibitor flurbiprofen reduces radiation-induced angiogenic growth factor secretion of squamous cell carcinoma cell lines. Ann N Y Acad Sci. 2004 Dec;1030:37-42.
• [62] Flurbiprofen, a cyclooxygenase inhibitor, protects mice from hepatic ischemia/reperfusion injury by inhibiting GSK-3 signaling and mitochondrial permeability transition.Mol Med.2012 Sep 25;18:1128-35.
• [63] Flurbiprofen: A Nonselective Cyclooxygenase (COX) Inhibitor for Treatment of Noninfectious, Non-necrotizing Anterior Scleritis.Ocul Immunol Inflamm.2016;24(1):35-42.
• [64] Structure-based design, synthesis, and biological evaluation of indomethacin derivatives as cyclooxygenase-2 inhibiting nitric oxide donors. J Med Chem. 2007 Dec 13;50(25):6367-82.
• [65] Pharmacokinetic and pharmacodynamic aspects of the ideal COX-2 inhibitor: a pharmacologist's perspective. Clin Exp Rheumatol. 2001 Nov-Dec;19(6 Suppl 25):S51-7.
• [66] Designed multiple ligands. An emerging drug discovery paradigm. J Med Chem. 2005 Oct 20;48(21):6523-43.
• [67] Diazen-1-ium-1,2-diolated nitric oxide donor ester prodrugs of 5-(4-hydroxymethylphenyl)-1-(4-aminosulfonylphenyl)-3-trifluoromethyl-1H-pyrazole an... Bioorg Med Chem. 2008 Nov 15;16(22):9694-8.
• [68] Selective synthesis and biological evaluation of sulfate-conjugated resveratrol metabolites. J Med Chem. 2010 Jul 8;53(13):5033-43.
• [69] Synthesis and antiinflammatory activity of coumarin derivatives. J Med Chem. 2005 Oct 6;48(20):6400-8.
• [70] 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. (Target id: 1375).
• [71] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [72] Divergent cyclooxygenase responses to fatty acid structure and peroxide level in fish and mammalian prostaglandin H synthases. FASEB J. 2006 Jun;20(8):1097-108.
• [73] Peroxidative free radical formation and O-demethylation of etoposide(VP-16) and teniposide(VM-26). Biochem Biophys Res Commun. 1986 Feb 26;135(1):215-20.
• [74] Identification and functional characterization of polymorphisms in human cyclooxygenase-1 (PTGS1). Pharmacogenet Genomics. 2007 Feb;17(2):145-60.