Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRX72TH)

• DOT Name: Aldo-keto reductase family 1 member B1 (AKR1B1)
• Synonyms: EC 1.1.1.300; EC 1.1.1.372; EC 1.1.1.54; Aldehyde reductase; Aldose reductase; AR; EC 1.1.1.21
• Gene Name: AKR1B1
• UniProt ID: ALDR_HUMAN
• PDB ID: 1ABN ; 1ADS ; 1AZ1 ; 1AZ2 ; 1EF3 ; 1EL3 ; 1IEI ; 1MAR ; 1PWL ; 1PWM ; 1T40 ; 1T41 ; 1US0 ; 1X96 ; 1X97 ; 1X98 ; 1XGD ; 1Z3N ; 1Z89 ; 1Z8A ; 2ACQ ; 2ACR ; 2ACS ; 2ACU ; 2AGT ; 2DUX ; 2DUZ ; 2DV0 ; 2F2K ; 2FZ8 ; 2FZ9 ; 2FZB ; 2FZD ; 2HV5 ; 2HVN ; 2HVO ; 2I16 ; 2I17 ; 2IKG ; 2IKH ; 2IKI ; 2IKJ ; 2INE ; 2INZ ; 2IPW ; 2IQ0 ; 2IQD ; 2IS7 ; 2ISF ; 2J8T ; 2NVC ; 2NVD ; 2PD5 ; 2PD9 ; 2PDB ; 2PDC ; 2PDF ; 2PDG ; 2PDH ; 2PDI ; 2PDJ ; 2PDK ; 2PDL ; 2PDM ; 2PDN ; 2PDP ; 2PDQ ; 2PDU ; 2PDW ; 2PDX ; 2PDY ; 2PEV ; 2PF8 ; 2PFH ; 2PZN ; 2QXW ; 2R24 ; 3BCJ ; 3DN5 ; 3G5E ; 3GHR ; 3GHS ; 3GHT ; 3GHU ; 3LBO ; 3LD5 ; 3LEN ; 3LEP ; 3LQG ; 3LQL ; 3LZ3 ; 3LZ5 ; 3M0I ; 3M4H ; 3M64 ; 3MB9 ; 3MC5 ; 3ONB ; 3ONC ; 3P2V ; 3Q65 ; 3Q67 ; 3RX2 ; 3RX3 ; 3RX4 ; 3S3G ; 3T42 ; 3U2C ; 3V35 ; 3V36 ; 4GCA ; 4GQ0 ; 4IGS ; 4JIR ; 4LAU ; 4LAZ ; 4LB3 ; 4LB4 ; 4LBR ; 4LBS ; 4NKC ; 4PR4 ; 4PRR ; 4PRT ; 4PUU ; 4PUW ; 4Q7B ; 4QBX ; 4QR6 ; 4QX4 ; 4QXI ; 4RPQ ; 4XZH ; 4XZI ; 4YS1 ; 4YU1 ; 5HA7 ; 5OU0 ; 5OUJ ; 5OUK ; 6F7R ; 6F81 ; 6F82 ; 6F84 ; 6F8O ; 6SYW ; 6T27 ; 6T3P ; 6T5G ; 6T7Q ; 6TD8 ; 6TUC ; 6TUF ; 6TXP ; 6XUM ; 6Y03 ; 6Y1P ; 8A4N ; 8AE9 ; 8AQG ; 8AQP ; 8AUU ; 8B34 ; 8B3N ; 8B3R ; 8B66 ; 8BJL
• EC Number: 1.1.1.21; 1.1.1.300; 1.1.1.372; 1.1.1.54
• Pfam ID: PF00248
• Sequence:
  MASRLLLNNGAKMPILGLGTWKSPPGQVTEAVKVAIDVGYRHIDCAHVYQNENEVGVAIQ
  EKLREQVVKREELFIVSKLWCTYHEKGLVKGACQKTLSDLKLDYLDLYLIHWPTGFKPGK
  EFFPLDESGNVVPSDTNILDTWAAMEELVDEGLVKAIGISNFNHLQVEMILNKPGLKYKP
  AVNQIECHPYLTQEKLIQYCQSKGIVVTAYSPLGSPDRPWAKPEDPSLLEDPRIKAIAAK
  HNKTTAQVLIRFPMQRNLVVIPKSVTPERIAENFKVFDFELSSQDMTTLLSYNRNWRVCA
  LLSCTSHKDYPFHEEF
• Function: Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols. Displays enzymatic activity towards endogenous metabolites such as aromatic and aliphatic aldehydes, ketones, monosacharides, bile acids and xenobiotics substrates. Key enzyme in the polyol pathway, catalyzes reduction of glucose to sorbitol during hyperglycemia. Reduces steroids and their derivatives and prostaglandins. Displays low enzymatic activity toward all-trans-retinal, 9-cis-retinal, and 13-cis-retinal. Catalyzes the reduction of diverse phospholipid aldehydes such as 1-palmitoyl-2-(5-oxovaleroyl)-sn -glycero-3-phosphoethanolamin (POVPC) and related phospholipid aldehydes that are generated from the oxydation of phosphotidylcholine and phosphatdyleethanolamides. Plays a role in detoxifying dietary and lipid-derived unsaturated carbonyls, such as crotonaldehyde, 4-hydroxynonenal, trans-2-hexenal, trans-2,4-hexadienal and their glutathione-conjugates carbonyls (GS-carbonyls).
• Tissue Specificity: Highly expressed in embryonic epithelial cells (EUE) in response to osmotic stress.
• KEGG Pathway:
  Pentose and glucuro.te interconversions (hsa00040)
  Fructose and mannose metabolism (hsa00051)
  Galactose metabolism (hsa00052)
  Glycerolipid metabolism (hsa00561)
  Folate biosynthesis (hsa00790)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Fructose biosynthesis (R-HSA-5652227)
  Pregnenolone biosynthesis (R-HSA-196108)
• BioCyc Pathway: MetaCyc:HS01502-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Aldo-keto reductase family 1 member B1 (AKR1B1) increases the response to substance of Paclitaxel.	[28]
DTI-015	DMXZRW0	Approved	Aldo-keto reductase family 1 member B1 (AKR1B1) affects the response to substance of DTI-015.	[29]
Capecitabine	DMTS85L	Approved	Aldo-keto reductase family 1 member B1 (AKR1B1) decreases the response to substance of Capecitabine.	[28]
Vitamin A	DMJ2AH4	Approved	Aldo-keto reductase family 1 member B1 (AKR1B1) decreases the response to substance of Vitamin A.	[31]

This DOT Affected the Biotransformations of 19 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Daunorubicin	DMQUSBT	Approved	Aldo-keto reductase family 1 member B1 (AKR1B1) increases the reduction of Daunorubicin.	[30]
Benzyl alcohol	DMBVYDI	Approved	Aldo-keto reductase family 1 member B1 (AKR1B1) increases the oxidation of Benzyl alcohol.	[21]
3-Hydroxy-2-butanone	DM9GPKR	Patented	Aldo-keto reductase family 1 member B1 (AKR1B1) increases the reduction of 3-Hydroxy-2-butanone.	[33]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	Aldo-keto reductase family 1 member B1 (AKR1B1) increases the reduction of 4-hydroxy-2-nonenal.	[30]
crotylaldehyde	DMTWRQI	Investigative	Aldo-keto reductase family 1 member B1 (AKR1B1) increases the reduction of crotylaldehyde.	[34]
acrolein	DMAMCSR	Investigative	Aldo-keto reductase family 1 member B1 (AKR1B1) increases the reduction of acrolein.	[30]
Octanal	DMTN0OK	Investigative	Aldo-keto reductase family 1 member B1 (AKR1B1) affects the reduction of Octanal.	[35]
methylglyoxal	DMRC3OZ	Investigative	Aldo-keto reductase family 1 member B1 (AKR1B1) increases the reduction of methylglyoxal.	[30]
Phenanthrene-9,10-dione	DMG8KS9	Investigative	Aldo-keto reductase family 1 member B1 (AKR1B1) increases the reduction of Phenanthrene-9,10-dione.	[30]
All-trans-retinal	DM6CEVB	Investigative	Aldo-keto reductase family 1 member B1 (AKR1B1) increases the reduction of All-trans-retinal.	[31]
1,2-NAPHTHOQUINONE	DMYXELH	Investigative	Aldo-keto reductase family 1 member B1 (AKR1B1) increases the reduction of 1,2-NAPHTHOQUINONE.	[30]
1H-Indole-2,3-dione	DMOZ91H	Investigative	Aldo-keto reductase family 1 member B1 (AKR1B1) increases the reduction of 1H-Indole-2,3-dione.	[30]
J-009747	DMQSB6N	Investigative	Aldo-keto reductase family 1 member B1 (AKR1B1) increases the reduction of J-009747.	[36]
Hexylacrolein	DMBC8KM	Investigative	Aldo-keto reductase family 1 member B1 (AKR1B1) increases the reduction of Hexylacrolein.	[36]
Phenylglyoxal	DMHW93J	Investigative	Aldo-keto reductase family 1 member B1 (AKR1B1) increases the reduction of Phenylglyoxal.	[30]
2,3-dihydroxypropanal	DMOWNB4	Investigative	Aldo-keto reductase family 1 member B1 (AKR1B1) increases the reduction of 2,3-dihydroxypropanal.	[31]
Nitrobenzaldehyde	DM4UHB5	Investigative	Aldo-keto reductase family 1 member B1 (AKR1B1) increases the reduction of Nitrobenzaldehyde.	[30]
Decanal	DMWZKLM	Investigative	Aldo-keto reductase family 1 member B1 (AKR1B1) increases the reduction of Decanal.	[36]
2-pentenal	DM032YM	Investigative	Aldo-keto reductase family 1 member B1 (AKR1B1) increases the reduction of 2-pentenal.	[36]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Sorbitol	DMAN0DE	Approved	Aldo-keto reductase family 1 member B1 (AKR1B1) increases the abundance of Sorbitol.	[32]

3 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 Aldo-keto reductase family 1 member B1 (AKR1B1).	[1]
Vitamin C	DMXJ7O8	Approved	Vitamin C increases the reduction of Aldo-keto reductase family 1 member B1 (AKR1B1).	[15]
Glutathione	DMAHMT9	Approved	Glutathione increases the glutathionylation of Aldo-keto reductase family 1 member B1 (AKR1B1).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Aldo-keto reductase family 1 member B1 (AKR1B1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Aldo-keto reductase family 1 member B1 (AKR1B1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Aldo-keto reductase family 1 member B1 (AKR1B1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Aldo-keto reductase family 1 member B1 (AKR1B1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Aldo-keto reductase family 1 member B1 (AKR1B1).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Aldo-keto reductase family 1 member B1 (AKR1B1).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Aldo-keto reductase family 1 member B1 (AKR1B1).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Aldo-keto reductase family 1 member B1 (AKR1B1).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Aldo-keto reductase family 1 member B1 (AKR1B1).	[10]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Aldo-keto reductase family 1 member B1 (AKR1B1).	[11]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Aldo-keto reductase family 1 member B1 (AKR1B1).	[12]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Aldo-keto reductase family 1 member B1 (AKR1B1).	[13]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Aldo-keto reductase family 1 member B1 (AKR1B1).	[14]
Benzoic acid	DMKB9FI	Approved	Benzoic acid increases the expression of Aldo-keto reductase family 1 member B1 (AKR1B1).	[14]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Aldo-keto reductase family 1 member B1 (AKR1B1).	[16]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Aldo-keto reductase family 1 member B1 (AKR1B1).	[14]
Disulfiram	DMCL2OK	Phase 2 Trial	Disulfiram increases the expression of Aldo-keto reductase family 1 member B1 (AKR1B1).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Aldo-keto reductase family 1 member B1 (AKR1B1).	[17]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Aldo-keto reductase family 1 member B1 (AKR1B1).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Aldo-keto reductase family 1 member B1 (AKR1B1).	[19]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of Aldo-keto reductase family 1 member B1 (AKR1B1).	[14]
ZOPOLRESTAT	DMWOT92	Discontinued in Phase 2	ZOPOLRESTAT decreases the activity of Aldo-keto reductase family 1 member B1 (AKR1B1).	[20]
MG-132	DMKA2YS	Preclinical	MG-132 increases the expression of Aldo-keto reductase family 1 member B1 (AKR1B1).	[13]
PIRINIXIC ACID	DM82Y75	Preclinical	PIRINIXIC ACID decreases the activity of Aldo-keto reductase family 1 member B1 (AKR1B1).	[21]
Sorbinil	DM31VE4	Terminated	Sorbinil decreases the activity of Aldo-keto reductase family 1 member B1 (AKR1B1).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Aldo-keto reductase family 1 member B1 (AKR1B1).	[22]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Aldo-keto reductase family 1 member B1 (AKR1B1).	[14]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Aldo-keto reductase family 1 member B1 (AKR1B1).	[23]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Aldo-keto reductase family 1 member B1 (AKR1B1).	[24]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the expression of Aldo-keto reductase family 1 member B1 (AKR1B1).	[10]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Aldo-keto reductase family 1 member B1 (AKR1B1).	[25]
Uric acid	DMA1MKT	Investigative	Uric acid increases the expression of Aldo-keto reductase family 1 member B1 (AKR1B1).	[26]
methyl salicylate	DMKCG8H	Investigative	methyl salicylate increases the expression of Aldo-keto reductase family 1 member B1 (AKR1B1).	[14]
2-Propanol, Isopropanol	DML5O0H	Investigative	2-Propanol, Isopropanol increases the expression of Aldo-keto reductase family 1 member B1 (AKR1B1).	[14]
Caffeic acid phenethyl ester	DMRJKIV	Investigative	Caffeic acid phenethyl ester decreases the activity of Aldo-keto reductase family 1 member B1 (AKR1B1).	[27]

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