Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTK0943)

• DTT Name: Prostaglandin G/H synthase (COX)
• Synonyms: Prostaglandin-endoperoxide synthase; Prostaglandin H2 synthase; PHS; PGHS; PGH synthase; Cyclooxygenase; COX
• Gene Name: PTGS1; PTGS2
• DTT Type: Successful target; [1]
• Related Disease:
  Cerebral ischaemia [ICD-11: 8B1Z]
  Hyper-lipoproteinaemia [ICD-11: 5C80]
  Inflammatory spondyloarthritis [ICD-11: FA92]
  Inherited coagulation factor deficiency [ICD-11: 3B14]
  Joint pain [ICD-11: ME82]
  Migraine [ICD-11: 8A80]
  Myocardial infarction [ICD-11: BA41-BA43]
  Osteoarthritis [ICD-11: FA00-FA05]
  Otitis media [ICD-11: AA80-AB0Z]
  Pain [ICD-11: MG30-MG3Z]
  Postoperative inflammation [ICD-11: 1A00-CA43]
  Rheumatoid arthritis [ICD-11: FA20]
  Spinal pain [ICD-11: ME84]
• BioChemical Class: Paired donor oxygen oxidoreductase
• UniProt ID: PGH1_HUMAN ; PGH2_HUMAN
• TTD ID: T03403
• Sequence:
  MSRSLLLWFLLFLLLLPPLPVLLADPGAPTPVNPCCYYPCQHQGICVRFGLDRYQCDCTR
  TGYSGPNCTIPGLWTWLRNSLRPSPSFTHFLLTHGRWFWEFVNATFIREMLMRLVLTVRS
  NLIPSPPTYNSAHDYISWESFSNVSYYTRILPSVPKDCPTPMGTKGKKQLPDAQLLARRF
  LLRRKFIPDPQGTNLMFAFFAQHFTHQFFKTSGKMGPGFTKALGHGVDLGHIYGDNLERQ
  YQLRLFKDGKLKYQVLDGEMYPPSVEEAPVLMHYPRGIPPQSQMAVGQEVFGLLPGLMLY
  ATLWLREHNRVCDLLKAEHPTWGDEQLFQTTRLILIGETIKIVIEEYVQQLSGYFLQLKF
  DPELLFGVQFQYRNRIAMEFNHLYHWHPLMPDSFKVGSQEYSYEQFLFNTSMLVDYGVEA
  LVDAFSRQIAGRIGGGRNMDHHILHVAVDVIRESREMRLQPFNEYRKRFGMKPYTSFQEL
  VGEKEMAAELEELYGDIDALEFYPGLLLEKCHPNSIFGESMIEIGAPFSLKGLLGNPICS
  PEYWKPSTFGGEVGFNIVKTATLKKLVCLNTKTCPYVSFRVPDASQDDGPAVERPSTEL
• Function: Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. PTGS1 is involved in the constitutive production of prostanoids in particular in the stomach and platelets. It is a key step in the generation of prostaglandins in gastric epithelial cells and the generation of thromboxane A2 (TXA2) in platelets. PTGS2 is constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and brain, and in pathological conditions, such as in cancer. PTGS2 is responsible for production of inflammatory prostaglandins. Up-regulation of PTGS2 is also associated with increased cell adhesion, phenotypic changes, resistance to apoptosis and tumor angiogenesis.
• KEGG Pathway:
  Arachidonic acid metabolism (hsa00590)
  Metabolic pathways (hsa01100)
  Platelet activation (hsa04611)
  Serotonergic synapse (hsa04726)
  Regulation of lipolysis in adipocytes (hsa04923)
• 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

20 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aceclofenac	DMZDF0B	Inflammation	1A00-CA43.1	Approved	[2], [3]
Acetaminophen	DMUIE76	Pain	MG30-MG3Z	Approved	[4], [5], [6]
Ampiroxicam	DM5BS98	Inflammation	1A00-CA43.1	Approved	[7], [3]
Amtolmetin guacil	DMAWU35	Inflammation	1A00-CA43.1	Approved	[8], [3]
Asasantin	DMCZIHT	Cerebrovascular ischaemia	8B1Z	Approved	[9]
Aspirin	DM672AH	Myocardial infarction	BA41-BA43	Approved	[10], [9]
Dexibuprofen	DMFYBD0	Ankylosing spondylitis	FA92.0	Approved	[11], [3]
Diclofenac	DMPIHLS	Osteoarthritis	FA00-FA05	Approved	[1], [3]
Felbinac	DMKZEIB	Arthritis	FA20	Approved	[12], [3]
Fenoprofen	DML5VQ0	Rheumatoid arthritis	FA20	Approved	[13], [14]
Fosfosal	DMDIC39	Pain	MG30-MG3Z	Approved	[15], [16]
Icosapent	DMJHN0A	Hyperglyceridemia	5C80.1	Approved	[17]
Ketorolac	DMI4EL5	Postoperative inflammation	1A00-CA43.1	Approved	[18]
Lornoxicam	DMYZFXN	Migraine	8A80	Approved	[19], [3]
Loxoprofen gel	DMQMGXV	Inflammation	1A00-CA43.1	Approved	[20], [3]
Meclofenamic acid	DM05FXR	Ankylosing spondylitis	FA92.0	Approved	[21], [22]
Morniflumate	DM9UTDE	Otitis media	AA80-AB0Z	Approved	[23], [3]
Nepafenac	DMYK490	Osteoarthritis	FA00-FA05	Approved	[24], [3]
Oxaprozin	DM9UB0P	Rheumatoid arthritis	FA20	Approved	[13]
Pelubiprofen	DM8DQV9	Back pain	ME84.Z	Approved	[25], [3]

8 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
K-103-IP	DM9J0KD	Pain	MG30-MG3Z	Phase 3	[26]
Naproxcinod	DMKP45D	Inflammation	1A00-CA43.1	Phase 3	[27]
BN82451	DMUM2KA	Parkinson disease	8A00.0	Phase 2	[28]
NCX 1022	DM4W28K	Atopic dermatitis	EA80	Phase 2	[29]
NCX-4016	DMOX1CU	Inflammation	1A00-CA43.1	Phase 2	[9]
TZI-41078	DMKJIDU	Arthritis	FA20	Phase 2	[30], [3]
4-aminosalicylate sodium	DM4Z1CH	Inflammatory bowel disease	DD72	Phase 1	[31]
SKF-105809	DMUN7EQ	Pain	MG30-MG3Z	Phase 1	[32]

19 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Droxicam	DMRZ5D7	Inflammation	1A00-CA43.1	Withdrawn from market	[33]
Zomepirac	DM7APNJ	Pain	MG30-MG3Z	Withdrawn from market	[34], [3]
Bermoprofen	DM7BN1A	Inflammation	1A00-CA43.1	Discontinued in Preregistration	[35]
Pirazolac	DMP6BG4	Inflammation	1A00-CA43.1	Discontinued in Preregistration	[36]
KC-764	DM1AFPW	Platelet aggregation disorder	3B62	Discontinued in Phase 3	[37], [3]
Benzydamine	DMEQL9U	Chemotherapy or radiotherapy-induced mucositis	DA42-DA60	Discontinued in Phase 2	[38]
D-7193	DMO9HWU	Immune System disease	4A01-4B41	Discontinued in Phase 2	[39]
FS-205-397	DMJLEV7	Pain	MG30-MG3Z	Discontinued in Phase 2	[40], [3]
NCX-701	DMWROJ5	Pain	MG30-MG3Z	Discontinued in Phase 2	[41], [42]
PSD-508	DMR1OJM	Dysmenorrhea	GA34.3	Discontinued in Phase 2	[43]
D-1367	DMB24V7	Arthritis	FA20	Discontinued in Phase 1	[44]
Eltenac	DMWRQG7	Arthritis	FA20	Discontinued in Phase 1	[45]
F-11105	DMLRF7U	Asthma	CA23	Discontinued in Phase 1	[39]
E-5110	DMR861Q	Inflammation	1A00-CA43.1	Terminated	[46]
Florifenine	DMDVAI5	Inflammation	1A00-CA43.1	Terminated	[47]
NMI-1182	DM5IFU9	Inflammation	1A00-CA43.1	Terminated	[48]
RP-66364	DM6HJX7	Inflammation	1A00-CA43.1	Terminated	[49]
S-14080	DM759KX	Inflammation	1A00-CA43.1	Terminated	[50]
WY-28342	DMAG86C	Rheumatoid arthritis	FA20	Terminated	[51]

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