Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTIY56R)

• DTT Name: Kynurenine 3-hydroxylase (KMO)
• Synonyms: Kynurenine 3monooxygenase; Kynurenine 3-monooxygenase
• Gene Name: KMO
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Paired donor oxygen oxidoreductase
• UniProt ID: KMO_HUMAN
• TTD ID: T50973
• EC Number: EC 1.14.13.9
• Sequence:
  MDSSVIQRKKVAVIGGGLVGSLQACFLAKRNFQIDVYEAREDTRVATFTRGRSINLALSH
  RGRQALKAVGLEDQIVSQGIPMRARMIHSLSGKKSAIPYGTKSQYILSVSRENLNKDLLT
  AAEKYPNVKMHFNHRLLKCNPEEGMITVLGSDKVPKDVTCDLIVGCDGAYSTVRSHLMKK
  PRFDYSQQYIPHGYMELTIPPKNGDYAMEPNYLHIWPRNTFMMIALPNMNKSFTCTLFMP
  FEEFEKLLTSNDVVDFFQKYFPDAIPLIGEKLLVQDFFLLPAQPMISVKCSSFHFKSHCV
  LLGDAAHAIVPFFGQGMNAGFEDCLVFDELMDKFSNDLSLCLPVFSRLRIPDDHAISDLS
  MYNYIEMRAHVNSSWFIFQKNMERFLHAIMPSTFIPLYTMVTFSRIRYHEAVQRWHWQKK
  VINKGLFFLGSLIAISSTYLLIHYMSPRSFLRLRRPWNWIAHFRNTTCFPAKAVDSLEQI
  SNLISR
• Function: Required for synthesis of quinolinic acid, a neurotoxic NMDA receptor antagonist and potential endogenous inhibitor of NMDA receptor signaling in axonal targeting, synaptogenesis and apoptosis during brain development. Quinolinic acid may also affect NMDA receptor signaling in pancreatic beta cells, osteoblasts, myocardial cells, and the gastrointestinal tract. Catalyzes the hydroxylation of L-kynurenine (L-Kyn) to form 3-hydroxy-L-kynurenine (L-3OHKyn).
• KEGG Pathway:
  Tryptophan metabolism (hsa00380)
  Metabolic pathways (hsa01100)
  Biosynthesis of cofactors (hsa01240)
• Reactome Pathway: Tryptophan catabolism (R-HSA-71240)
• BioCyc Pathway: MetaCyc:HS04082-MON

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GSK065	DMO87YS	Pancreatitis	DC31-DC34	Phase 1	[2]

36 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aryl pyrimidine derivative 2	DMU9Y4B	N. A.	N. A.	Patented	[1]
Aryl pyrimidine derivative 3	DMXND26	N. A.	N. A.	Patented	[1]
Aryl pyrimidine derivative 4	DMWSAL5	N. A.	N. A.	Patented	[1]
Aryl pyrimidine derivative 5	DMEP9O8	N. A.	N. A.	Patented	[1]
Aryl pyrimidine derivative 6	DMMF9U6	N. A.	N. A.	Patented	[1]
Aryl pyrimidine derivative 7	DM8FAW3	N. A.	N. A.	Patented	[1]
Aryl pyrimidine derivative 8	DM7OA9E	N. A.	N. A.	Patented	[1]
Aryl pyrimidine derivative 9	DMBEYD1	N. A.	N. A.	Patented	[1]
Benzene sulfonamide derivative 1	DMB9VEH	N. A.	N. A.	Patented	[1]
Benzene sulfonamide derivative 2	DMUZQLR	N. A.	N. A.	Patented	[1]
Benzene sulfonamide derivative 3	DMCQLJY	N. A.	N. A.	Patented	[1]
Benzene sulfonamide derivative 4	DMXCUEG	N. A.	N. A.	Patented	[1]
Benzene sulfonamide derivative 5	DMW4NXV	N. A.	N. A.	Patented	[1]
Benzene sulfonamide derivative 6	DMD4UMP	N. A.	N. A.	Patented	[1]
Benzene sulfonamide derivative 7	DM0TKP2	N. A.	N. A.	Patented	[1]
Cyclopropane 1-carboxylic acid derivative 1	DMNXBPQ	N. A.	N. A.	Patented	[1]
Cyclopropane 1-carboxylic acid derivative 10	DM3M169	N. A.	N. A.	Patented	[1]
Cyclopropane 1-carboxylic acid derivative 2	DMSXB58	N. A.	N. A.	Patented	[1]
Cyclopropane 1-carboxylic acid derivative 3	DM6K59I	N. A.	N. A.	Patented	[1]
Cyclopropane 1-carboxylic acid derivative 4	DM8PVN3	N. A.	N. A.	Patented	[1]
Cyclopropane 1-carboxylic acid derivative 5	DMCSIYG	N. A.	N. A.	Patented	[1]
Cyclopropane 1-carboxylic acid derivative 6	DM0OMBW	N. A.	N. A.	Patented	[1]
Cyclopropane 1-carboxylic acid derivative 7	DM4RTMO	N. A.	N. A.	Patented	[1]
Cyclopropane 1-carboxylic acid derivative 8	DM4P9HL	N. A.	N. A.	Patented	[1]
Cyclopropane 1-carboxylic acid derivative 9	DMLH9AQ	N. A.	N. A.	Patented	[1]
Isoxazoles and isoxazoline derivative 1	DMRML9B	N. A.	N. A.	Patented	[1]
Isoxazoles and isoxazoline derivative 2	DMKCYSD	N. A.	N. A.	Patented	[1]
Isoxazoles and isoxazoline derivative 3	DMULJOS	N. A.	N. A.	Patented	[1]
Isoxazoles and isoxazoline derivative 4	DMW3JZV	N. A.	N. A.	Patented	[1]
Isoxazoles and isoxazoline derivative 5	DMCWFU1	N. A.	N. A.	Patented	[1]
Isoxazoles and isoxazoline derivative 6	DMIKBV5	N. A.	N. A.	Patented	[1]
PMID27172114-Compound-47	DMTIQYD	N. A.	N. A.	Patented	[1]
PMID27172114-Compound-49	DMSXJVY	N. A.	N. A.	Patented	[1]
Pyrimidine benzenesulfonamide derivative 1	DMD6GNO	N. A.	N. A.	Patented	[1]
Pyrimidine benzenesulfonamide derivative 2	DMVQ4NS	N. A.	N. A.	Patented	[1]
Pyrimidine benzenesulfonamide derivative 3	DMJ71Q0	N. A.	N. A.	Patented	[1]

5 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CHDI-340246	DMYGITU	Huntington disease	8A01.10	Preclinical	[3]
GSK180	DMNU3SI	Neurodegenerative disorder	8A20-8A23	Preclinical	[4]
GSK366	DM04UGQ	Pancreatitis	DC31-DC34	Preclinical	[2]
Ro 61-8048	DMWAR1T	Neurodegenerative disorder	8A20-8A23	Preclinical	[5]
UPF-648	DMDVZQ8	Neurodegenerative disorder	8A20-8A23	Preclinical	[6]

References

• [1] Inhibitors of the kynurenine pathway as neurotherapeutics: a patent review (2012-2015).Expert Opin Ther Pat. 2016 Jul;26(7):815-32.
• [2] Structural and mechanistic basis of differentiated inhibitors of the acute pancreatitis target kynurenine-3-monooxygenase. Nat Commun. 2017 Jun 12;8:15827.
• [3] The novel KMO inhibitor CHDI-340246 leads to a restoration of electrophysiological alterations in mouse models of Huntington's disease. Exp Neurol. 2016 Aug;282:99-118.
• [4] Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond. Nat Rev Drug Discov. 2019 May;18(5):379-401.
• [5] Modification of kynurenine pathway via inhibition of kynurenine hydroxylase attenuates surgical brain injury complications in a male rat model. J Neurosci Res. 2020 Jan;98(1):155-167.
• [6] Structural basis of kynurenine 3-monooxygenase inhibition. Nature. 2013 Apr 18;496(7445):382-5.