Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTINL2RE)

• DOT Name: Kynureninase (KYNU)
• Synonyms: EC 3.7.1.3; L-kynurenine hydrolase
• Gene Name: KYNU
• Related Disease:
  Vertebral, cardiac, renal, and limb defects syndrome 2
  Encephalopathy due to hydroxykynureninuria
  Congenital vertebral-cardiac-renal anomalies syndrome
• UniProt ID: KYNU_HUMAN
• PDB ID: 2HZP; 3E9K; 7S3V
• EC Number: 3.7.1.3
• Pfam ID: PF00266
• Sequence:
  MEPSSLELPADTVQRIAAELKCHPTDERVALHLDEEDKLRHFRECFYIPKIQDLPPVDLS
  LVNKDENAIYFLGNSLGLQPKMVKTYLEEELDKWAKIAAYGHEVGKRPWITGDESIVGLM
  KDIVGANEKEIALMNALTVNLHLLMLSFFKPTPKRYKILLEAKAFPSDHYAIESQLQLHG
  LNIEESMRMIKPREGEETLRIEDILEVIEKEGDSIAVILFSGVHFYTGQHFNIPAITKAG
  QAKGCYVGFDLAHAVGNVELYLHDWGVDFACWCSYKYLNAGAGGIAGAFIHEKHAHTIKP
  ALVGWFGHELSTRFKMDNKLQLIPGVCGFRISNPPILLVCSLHASLEIFKQATMKALRKK
  SVLLTGYLEYLIKHNYGKDKAATKKPVVNIITPSHVEERGCQLTITFSVPNKDVFQELEK
  RGVVCDKRNPNGIRVAPVPLYNSFHDVYKFTNLLTSILDSAETKN
• Function: Catalyzes the cleavage of L-kynurenine (L-Kyn) and L-3-hydroxykynurenine (L-3OHKyn) into anthranilic acid (AA) and 3-hydroxyanthranilic acid (3-OHAA), respectively. Has a preference for the L-3-hydroxy form. Also has cysteine-conjugate-beta-lyase activity.
• Tissue Specificity: Expressed in all tissues tested (heart, brain placenta, lung, liver, skeletal muscle, kidney and pancreas). Highest levels found in placenta, liver and lung. Expressed in all brain regions.
• KEGG Pathway:
  Tryptophan metabolism (hsa00380)
  Metabolic pathways (hsa01100)
  Biosynthesis of cofactors (hsa01240)
• Reactome Pathway: Tryptophan catabolism (R-HSA-71240)
• BioCyc Pathway: MetaCyc:HS03952-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Vertebral, cardiac, renal, and limb defects syndrome 2	DIS6SEVJ	Definitive	Autosomal recessive	[1]
Encephalopathy due to hydroxykynureninuria	DISYCGPA	Strong	Autosomal recessive	[2]
Congenital vertebral-cardiac-renal anomalies syndrome	DISR2YKP	Supportive	Autosomal recessive	[3]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Kynureninase (KYNU) affects the response to substance of Etoposide.	[34]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Kynureninase (KYNU).	[4]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Kynureninase (KYNU).	[28]

33 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Kynureninase (KYNU).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Kynureninase (KYNU).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Kynureninase (KYNU).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Kynureninase (KYNU).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Kynureninase (KYNU).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Kynureninase (KYNU).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Kynureninase (KYNU).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Kynureninase (KYNU).	[12]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Kynureninase (KYNU).	[13]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Kynureninase (KYNU).	[14]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Kynureninase (KYNU).	[15]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Kynureninase (KYNU).	[16]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of Kynureninase (KYNU).	[17]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Kynureninase (KYNU).	[18]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Kynureninase (KYNU).	[19]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Kynureninase (KYNU).	[20]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Kynureninase (KYNU).	[19]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Kynureninase (KYNU).	[21]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Kynureninase (KYNU).	[22]
Estrone	DM5T6US	Approved	Estrone decreases the expression of Kynureninase (KYNU).	[19]
Mestranol	DMG3F94	Approved	Mestranol decreases the expression of Kynureninase (KYNU).	[19]
Gamolenic acid	DMQN30Z	Approved	Gamolenic acid decreases the expression of Kynureninase (KYNU).	[23]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Kynureninase (KYNU).	[24]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Kynureninase (KYNU).	[25]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Kynureninase (KYNU).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Kynureninase (KYNU).	[26]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Kynureninase (KYNU).	[27]
HEXESTROL	DM9AGWQ	Withdrawn from market	HEXESTROL decreases the expression of Kynureninase (KYNU).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Kynureninase (KYNU).	[29]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Kynureninase (KYNU).	[30]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Kynureninase (KYNU).	[31]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Kynureninase (KYNU).	[32]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Kynureninase (KYNU).	[33]

References

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