Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU2SXBA)

DOT Name Aldo-keto reductase family 1 member C3 (AKR1C3)
Synonyms
EC 1.1.1.-; EC 1.1.1.210; EC 1.1.1.53; EC 1.1.1.62; 17-beta-hydroxysteroid dehydrogenase type 5; 17-beta-HSD 5; 3-alpha-HSD type II, brain; 3-alpha-hydroxysteroid dehydrogenase type 2; 3-alpha-HSD type 2; EC 1.1.1.357; Chlordecone reductase homolog HAKRb; Dihydrodiol dehydrogenase 3; DD-3; DD3; Dihydrodiol dehydrogenase type I; HA1753; Prostaglandin F synthase; PGFS; EC 1.1.1.188; Testosterone 17-beta-dehydrogenase 5; EC 1.1.1.239, EC 1.1.1.64
Gene Name AKR1C3
UniProt ID
AK1C3_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1RY0 ; 1RY8 ; 1S1P ; 1S1R ; 1S2A ; 1S2C ; 1XF0 ; 1ZQ5 ; 2F38 ; 2FGB ; 3R43 ; 3R58 ; 3R6I ; 3R7M ; 3R8G ; 3R8H ; 3R94 ; 3UFY ; 3UG8 ; 3UGR ; 3UWE ; 4DBS ; 4DBU ; 4DBW ; 4DZ5 ; 4FA3 ; 4FAL ; 4FAM ; 4H7C ; 4HMN ; 4WDT ; 4WDU ; 4WDW ; 4WDX ; 4WRH ; 4XVD ; 4XVE ; 4YVV ; 4YVX ; 4ZFC ; 5HNT ; 5HNU ; 6A7B ; 6F2U ; 6F78 ; 6GXK ; 7C7F ; 7C7G ; 7C7H ; 7WQM ; 7WQR ; 7WQS ; 7X3L ; 7X3M ; 7X3O ; 8BBS ; 8I0C
EC Number
1.1.1.-; 1.1.1.188; 1.1.1.210; 1.1.1.239; 1.1.1.357; 1.1.1.53; 1.1.1.62; 1.1.1.64
Pfam ID
PF00248
Sequence
MDSKHQCVKLNDGHFMPVLGFGTYAPPEVPRSKALEVTKLAIEAGFRHIDSAHLYNNEEQ
VGLAIRSKIADGSVKREDIFYTSKLWSTFHRPELVRPALENSLKKAQLDYVDLYLIHSPM
SLKPGEELSPTDENGKVIFDIVDLCTTWEAMEKCKDAGLAKSIGVSNFNRRQLEMILNKP
GLKYKPVCNQVECHPYFNRSKLLDFCKSKDIVLVAYSALGSQRDKRWVDPNSPVLLEDPV
LCALAKKHKRTPALIALRYQLQRGVVVLAKSYNEQRIRQNVQVFEFQLTAEDMKAIDGLD
RNLHYFNSDSFASHPNYPYSDEY
Function
Cytosolic aldo-keto reductase that catalyzes the NADH and NADPH-dependent reduction of ketosteroids to hydroxysteroids. Acts as a NAD(P)(H)-dependent 3-, 17- and 20-ketosteroid reductase on the steroid nucleus and side chain and regulates the metabolism of androgens, estrogens and progesterone. Displays the ability to catalyze both oxidation and reduction in vitro, but most probably acts as a reductase in vivo since the oxidase activity measured in vitro is inhibited by physiological concentration of NADPH. Acts preferentially as a 17-ketosteroid reductase and has the highest catalytic efficiency of the AKR1C enzyme for the reduction of delta4-androstenedione to form testosterone. Reduces prostaglandin (PG) D2 to 11beta-prostaglandin F2, progesterone to 20alpha-hydroxyprogesterone and estrone to 17beta-estradiol. Catalyzes the transformation of the potent androgen dihydrotestosterone (DHT) into the less active form, 5-alpha-androstan-3-alpha,17-beta-diol (3-alpha-diol). Also displays retinaldehyde reductase activity toward 9-cis-retinal.
Tissue Specificity
Expressed in many tissues including adrenal gland, brain, kidney, liver, lung, mammary gland, placenta, small intestine, colon, spleen, prostate and testis. High expression in prostate and mammary gland. In the prostate, higher levels in epithelial cells than in stromal cells. In the brain, expressed in medulla, spinal cord, frontotemporal lobes, thalamus, subthalamic nuclei and amygdala. Weaker expression in the hippocampus, substantia nigra and caudate.
KEGG Pathway
Steroid hormone biosynthesis (hsa00140 )
Arachidonic acid metabolism (hsa00590 )
Folate biosynthesis (hsa00790 )
Metabolic pathways (hsa01100 )
Ovarian steroidogenesis (hsa04913 )
Chemical carcinogenesis - reactive oxygen species (hsa05208 )
Reactome Pathway
Synthesis of bile acids and bile salts via 24-hydroxycholesterol (R-HSA-193775 )
Synthesis of bile acids and bile salts via 27-hydroxycholesterol (R-HSA-193807 )
Synthesis of Prostaglandins (PG) and Thromboxanes (TX) (R-HSA-2162123 )
RA biosynthesis pathway (R-HSA-5365859 )
Retinoid metabolism and transport (R-HSA-975634 )
Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol (R-HSA-193368 )
BioCyc Pathway
MetaCyc:HS03054-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 3 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Hydrogen peroxide DM1NG5W Approved Aldo-keto reductase family 1 member C3 (AKR1C3) increases the response to substance of Hydrogen peroxide. [56]
Daunorubicin DMQUSBT Approved Aldo-keto reductase family 1 member C3 (AKR1C3) decreases the response to substance of Daunorubicin. [58]
Capecitabine DMTS85L Approved Aldo-keto reductase family 1 member C3 (AKR1C3) increases the response to substance of Capecitabine. [59]
------------------------------------------------------------------------------------
This DOT Affected the Regulation of Drug Effects of 5 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Testosterone DM7HUNW Approved Aldo-keto reductase family 1 member C3 (AKR1C3) increases the abundance of Testosterone. [57]
Estrone DM5T6US Approved Aldo-keto reductase family 1 member C3 (AKR1C3) increases the metabolism of Estrone. [21]
Dihydrotestosterone DM3S8XC Phase 4 Aldo-keto reductase family 1 member C3 (AKR1C3) increases the metabolism of Dihydrotestosterone. [61]
4-ANDROSTENE-3-17-DIONE DMSE8NU Investigative Aldo-keto reductase family 1 member C3 (AKR1C3) increases the metabolism of 4-ANDROSTENE-3-17-DIONE. [21]
PGD2 DMYDW6J Investigative Aldo-keto reductase family 1 member C3 (AKR1C3) decreases the metabolism of PGD2. [65]
------------------------------------------------------------------------------------
This DOT Affected the Biotransformations of 6 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Oxcarbazepine DM5PU6O Approved Aldo-keto reductase family 1 member C3 (AKR1C3) increases the reduction of Oxcarbazepine. [60]
ELTANOLONE DM38CIV Discontinued in Phase 3 Aldo-keto reductase family 1 member C3 (AKR1C3) increases the chemical synthesis of ELTANOLONE. [62]
Nitrobenzanthrone DMN6L70 Investigative Aldo-keto reductase family 1 member C3 (AKR1C3) increases the reduction of Nitrobenzanthrone. [63]
Farnesol DMV2X1B Investigative Aldo-keto reductase family 1 member C3 (AKR1C3) increases the chemical synthesis of Farnesol. [40]
All-trans-retinal DM6CEVB Investigative Aldo-keto reductase family 1 member C3 (AKR1C3) increases the reduction of All-trans-retinal. [64]
Acenaphthenol DMT3QYZ Investigative Aldo-keto reductase family 1 member C3 (AKR1C3) increases the oxidation of Acenaphthenol. [64]
------------------------------------------------------------------------------------
⏷ Show the Full List of 6 Drug(s)
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 Aldo-keto reductase family 1 member C3 (AKR1C3). [1]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of Aldo-keto reductase family 1 member C3 (AKR1C3). [44]
------------------------------------------------------------------------------------
91 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 C3 (AKR1C3). [2]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [3]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [4]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [5]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [6]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [7]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [8]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [9]
Arsenic DMTL2Y1 Approved Arsenic increases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [10]
Quercetin DM3NC4M Approved Quercetin decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [11]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [12]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [13]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [14]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [15]
Phenobarbital DMXZOCG Approved Phenobarbital increases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [16]
Progesterone DMUY35B Approved Progesterone decreases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [17]
Fluorouracil DMUM7HZ Approved Fluorouracil affects the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [18]
Dexamethasone DMMWZET Approved Dexamethasone increases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [19]
Bortezomib DMNO38U Approved Bortezomib increases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [20]
Aspirin DM672AH Approved Aspirin decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [21]
Testosterone enanthate DMB6871 Approved Testosterone enanthate affects the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [22]
Sodium lauryl sulfate DMLJ634 Approved Sodium lauryl sulfate decreases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [23]
Dasatinib DMJV2EK Approved Dasatinib increases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [24]
Indomethacin DMSC4A7 Approved Indomethacin decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [25]
Simvastatin DM30SGU Approved Simvastatin decreases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [26]
Sulindac DM2QHZU Approved Sulindac decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [21]
Ibuprofen DM8VCBE Approved Ibuprofen decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [21]
Liothyronine DM6IR3P Approved Liothyronine increases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [27]
Ursodeoxycholic acid DMCUT21 Approved Ursodeoxycholic acid decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [28]
Bexarotene DMOBIKY Approved Bexarotene increases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [29]
Benzoic acid DMKB9FI Approved Benzoic acid increases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [30]
Flurbiprofen DMGN4BY Approved Flurbiprofen decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [21]
Mefenamic acid DMK7HFI Approved Mefenamic acid decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [21]
Naproxen DMZ5RGV Approved Naproxen decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [21]
Diazepam DM08E9O Approved Diazepam decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [31]
Salicyclic acid DM2F8XZ Approved Salicyclic acid decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [21]
Benzbromarone DMC3YUA Approved Benzbromarone decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [28]
Dutasteride DMQ4TJK Approved Dutasteride increases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [32]
Glibenclamide DM8JXPZ Approved Glibenclamide decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [33]
Glimepiride DM5FSJA Approved Glimepiride decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [33]
Flunitrazepam DMGR5Z3 Approved Flunitrazepam decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [31]
Norethindrone DMTY169 Approved Norethindrone decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [34]
Levonorgestrel DM1DP7T Approved Levonorgestrel decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [34]
Flufenamic Acid DMC8VNH Approved Flufenamic Acid decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [28]
Dydrogesterone DMAKIDV Approved Dydrogesterone decreases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [17]
Meclofenamic acid DM05FXR Approved Meclofenamic acid decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [21]
Desogestrel DM27U4Y Approved Desogestrel decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [34]
Midostaurin DMI6E0R Approved Midostaurin decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [35]
Glipizide DMZA5PQ Approved Glipizide decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [33]
Gliquidone DMB0EUX Approved Gliquidone decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [33]
Nitrazepam DMEGIQ6 Approved Nitrazepam decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [31]
Estazolam DMZGXUM Approved Estazolam decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [31]
Enasidenib DM8QXOC Approved Enasidenib decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [36]
Bromazepam DMY9TCW Approved Bromazepam decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [31]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [37]
Seocalcitol DMKL9QO Phase 3 Seocalcitol increases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [38]
DNCB DMDTVYC Phase 2 DNCB increases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [30]
GSK2110183 DMZHB37 Phase 2 GSK2110183 increases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [39]
Disulfiram DMCL2OK Phase 2 Trial Disulfiram increases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [30]
GEA-6414 DM8J0MK Phase 1/2 GEA-6414 decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [40]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [41]
Eugenol DM7US1H Patented Eugenol increases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [30]
4-Hydroxybenzoicacid DM3WQNY Patented 4-Hydroxybenzoicacid decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [42]
HEXESTROL DM9AGWQ Withdrawn from market HEXESTROL decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [28]
Zomepirac DM7APNJ Withdrawn from market Zomepirac decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [21]
Phenolphthalein DM5SICT Withdrawn from market Phenolphthalein decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [28]
MG-132 DMKA2YS Preclinical MG-132 increases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [20]
EMODIN DMAEDQG Terminated EMODIN decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [43]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [45]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [46]
Milchsaure DM462BT Investigative Milchsaure increases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [30]
Sulforaphane DMQY3L0 Investigative Sulforaphane increases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [47]
Deguelin DMXT7WG Investigative Deguelin increases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [48]
3R14S-OCHRATOXIN A DM2KEW6 Investigative 3R14S-OCHRATOXIN A decreases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [49]
4-hydroxy-2-nonenal DM2LJFZ Investigative 4-hydroxy-2-nonenal increases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [50]
Butanoic acid DMTAJP7 Investigative Butanoic acid increases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [41]
Forskolin DM6ITNG Investigative Forskolin decreases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [51]
crotylaldehyde DMTWRQI Investigative crotylaldehyde increases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [52]
DM9CEI5 decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [28]
methylglyoxal DMRC3OZ Investigative methylglyoxal increases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [53]
Aloe-emodin DMPTY8S Investigative Aloe-emodin decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [43]
Phenanthrene-9,10-dione DMG8KS9 Investigative Phenanthrene-9,10-dione increases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [54]
methyl salicylate DMKCG8H Investigative methyl salicylate increases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [30]
2-Propanol, Isopropanol DML5O0H Investigative 2-Propanol, Isopropanol increases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [30]
Caffeic acid phenethyl ester DMRJKIV Investigative Caffeic acid phenethyl ester decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [42]
7-hydroxycoumarin DMTMNO7 Investigative 7-hydroxycoumarin increases the expression of Aldo-keto reductase family 1 member C3 (AKR1C3). [55]
NSC-94258 DM6VY3P Investigative NSC-94258 decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [11]
18beta-Glycyrrhetic acid DMFMRN8 Investigative 18beta-Glycyrrhetic acid decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [28]
Medazepam DMNKSX3 Investigative Medazepam decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [31]
diphenylamine-2-carboxylic acid DMBV19T Investigative diphenylamine-2-carboxylic acid decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [21]
OCTYL_GALLATE DMXLGUS Investigative OCTYL_GALLATE decreases the activity of Aldo-keto reductase family 1 member C3 (AKR1C3). [42]
------------------------------------------------------------------------------------
⏷ Show the Full List of 91 Drug(s)

References

1 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
2 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
3 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
4 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
5 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
6 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
7 Pathophysiological roles of aldo-keto reductases (AKR1C1 and AKR1C3) in development of cisplatin resistance in human colon cancers. Chem Biol Interact. 2013 Feb 25;202(1-3):234-42.
8 Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
9 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
10 Inorganic arsenic exposure promotes malignant progression by HDAC6-mediated down-regulation of HTRA1. J Appl Toxicol. 2023 Aug;43(8):1214-1224. doi: 10.1002/jat.4457. Epub 2023 Mar 11.
11 AKR1C3 as a potential target for the inhibitory effect of dietary flavonoids. Chem Biol Interact. 2009 Mar 16;178(1-3):138-44.
12 Global effects of inorganic arsenic on gene expression profile in human macrophages. Mol Immunol. 2009 Feb;46(4):649-56.
13 Gene microarray analysis of human renal cell carcinoma: the effects of HDAC inhibition and retinoid treatment. Cancer Biol Ther. 2008 Oct;7(10):1607-18.
14 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
15 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
16 Proteomic analysis of hepatic effects of phenobarbital in mice with humanized liver. Arch Toxicol. 2022 Oct;96(10):2739-2754. doi: 10.1007/s00204-022-03338-7. Epub 2022 Jul 26.
17 Progestin effects on expression of AKR1C1-AKR1C3, SRD5A1 and PGR in the Z-12 endometriotic epithelial cell line. Chem Biol Interact. 2013 Feb 25;202(1-3):218-25.
18 Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer. BMC Genomics. 2006 Apr 3;7:68. doi: 10.1186/1471-2164-7-68.
19 Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
20 Proteasome inhibitors MG-132 and bortezomib induce AKR1C1, AKR1C3, AKR1B1, and AKR1B10 in human colon cancer cell lines SW-480 and HT-29. Chem Biol Interact. 2011 May 30;191(1-3):239-49.
21 Type 5 17beta-hydroxysteroid dehydrogenase/prostaglandin F synthase (AKR1C3): role in breast cancer and inhibition by non-steroidal anti-inflammatory drug analogs. Chem Biol Interact. 2009 Mar 16;178(1-3):221-7.
22 Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
23 CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
24 Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
25 An indomethacin analogue, N-(4-chlorobenzoyl)-melatonin, is a selective inhibitor of aldo-keto reductase 1C3 (type 2 3alpha-HSD, type 5 17beta-HSD, and prostaglandin F synthase), a potential target for the treatment of hormone dependent and hormone independent malignancies. Biochem Pharmacol. 2008 Jan 15;75(2):484-93.
26 In-vivo effects of simvastatin and rosuvastatin on global gene expression in peripheral blood leucocytes in a human inflammation model. Pharmacogenet Genomics. 2008 Feb;18(2):109-20.
27 Thyroid hormone responsive genes in cultured human fibroblasts. J Clin Endocrinol Metab. 2005 Feb;90(2):936-43.
28 Selective and potent inhibitors of human 20alpha-hydroxysteroid dehydrogenase (AKR1C1) that metabolizes neurosteroids derived from progesterone. Chem Biol Interact. 2003 Feb 1;143-144:503-13.
29 Identification of biomarkers modulated by the rexinoid LGD1069 (bexarotene) in human breast cells using oligonucleotide arrays. Cancer Res. 2006 Dec 15;66(24):12009-18.
30 Keratinocyte gene expression profiles discriminate sensitizing and irritating compounds. Toxicol Sci. 2010 Sep;117(1):81-9.
31 Substrate specificity of human 3(20)alpha-hydroxysteroid dehydrogenase for neurosteroids and its inhibition by benzodiazepines. Biol Pharm Bull. 2002 Apr;25(4):441-5.
32 Dutasteride affects progesterone metabolizing enzyme activity/expression in human breast cell lines resulting in suppression of cell proliferation and detachment. J Steroid Biochem Mol Biol. 2006 Aug;100(4-5):129-40.
33 Initro inhibition of AKR1Cs by sulphonylureas and the structural basis. Chem Biol Interact. 2015 Oct 5;240:310-5.
34 Progestins as inhibitors of the human 20-ketosteroid reductases, AKR1C1 and AKR1C3. Chem Biol Interact. 2011 May 30;191(1-3):227-33.
35 Selective inhibition of aldo-keto reductase 1C3: a novel mechanism involved in midostaurin and daunorubicin synergism. Arch Toxicol. 2021 Jan;95(1):67-78. doi: 10.1007/s00204-020-02884-2. Epub 2020 Oct 6.
36 Isocitrate dehydrogenase 2 inhibitor enasidenib synergizes daunorubicin cytotoxicity by targeting aldo-keto reductase 1C3 and ATP-binding cassette transporters. Arch Toxicol. 2022 Dec;96(12):3265-3277. doi: 10.1007/s00204-022-03359-2. Epub 2022 Aug 16.
37 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
38 Expression profiling in squamous carcinoma cells reveals pleiotropic effects of vitamin D3 analog EB1089 signaling on cell proliferation, differentiation, and immune system regulation. Mol Endocrinol. 2002 Jun;16(6):1243-56.
39 Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
40 Roles of rat and human aldo-keto reductases in metabolism of farnesol and geranylgeraniol. Chem Biol Interact. 2011 May 30;191(1-3):261-8. doi: 10.1016/j.cbi.2010.12.017. Epub 2010 Dec 25.
41 Butyrate interacts with benzo[a]pyrene to alter expression and activities of xenobiotic metabolizing enzymes involved in metabolism of carcinogens within colon epithelial cell models. Toxicology. 2019 Jan 15;412:1-11.
42 Initro CAPE inhibitory activity towards human AKR1C3 and the molecular basis. Chem Biol Interact. 2016 Jun 25;253:60-5.
43 Inhibition of human carbonyl reducing enzymes by plant anthrone and anthraquinone derivatives. Chem Biol Interact. 2022 Feb 25;354:109823. doi: 10.1016/j.cbi.2022.109823. Epub 2022 Jan 21.
44 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
45 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
46 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
47 Transcriptomic responses of cancerous and noncancerous human colon cells to sulforaphane and selenium. Chem Res Toxicol. 2014 Mar 17;27(3):377-86.
48 Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
49 Ochratoxin a lowers mRNA levels of genes encoding for key proteins of liver cell metabolism. Cancer Genomics Proteomics. 2008 Nov-Dec;5(6):319-32.
50 Protective effect of inducible aldo-keto reductases on 4-hydroxynonenal- induced hepatotoxicity. Chem Biol Interact. 2019 May 1;304:124-130.
51 Steroid profiling in H295R cells to identify chemicals potentially disrupting the production of adrenal steroids. Toxicology. 2017 Apr 15;381:51-63.
52 Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde. Toxicol Lett. 2010 Aug 16;197(2):113-22.
53 Nrf2-mediated adaptive response to methyl glyoxal in HepG2 cells involves the induction of AKR7A2. Chem Biol Interact. 2015 Jun 5;234:366-71.
54 Facilitation of 9,10-phenanthrenequinone-elicited neuroblastoma cell apoptosis by NAD(P)H:quinone oxidoreductase 1. Chem Biol Interact. 2018 Jan 5;279:10-20.
55 Hepatoprotective effect of 7-hydroxycoumarin against methyl glyoxal toxicity via activation of Nrf2. Chem Biol Interact. 2017 Oct 1;276:203-209.
56 Inducible protection of human astrocytoma 1321N1 cells against hydrogen peroxide and aldehyde toxicity by 7-hydroxycoumarin is associated with the upregulation of aldo-keto reductases. Neurotoxicology. 2012 Oct;33(5):1368-74.
57 Identification of a functional polymorphism of the human type 5 17beta-hydroxysteroid dehydrogenase gene associated with polycystic ovary syndrome. J Clin Endocrinol Metab. 2006 Jan;91(1):270-6. doi: 10.1210/jc.2005-2012. Epub 2005 Nov 1.
58 Aldo-keto reductase 1C3 (AKR1C3): a missing piece of the puzzle in the dinaciclib interaction profile. Arch Toxicol. 2018 Sep;92(9):2845-2857.
59 Gene expression analysis using human cancer xenografts to identify novel predictive marker genes for the efficacy of 5-fluorouracil-based drugs. Cancer Sci. 2006 Jun;97(6):510-22. doi: 10.1111/j.1349-7006.2006.00204.x.
60 The role of carbonyl reducing enzymes in oxcarbazepine in vitro metabolism in man. Chem Biol Interact. 2014 Sep 5;220:241-7.
61 Human cytosolic 3alpha-hydroxysteroid dehydrogenases of the aldo-keto reductase superfamily display significant 3beta-hydroxysteroid dehydrogenase activity: implications for steroid hormone metabolism and action. J Biol Chem. 2004 Mar 12;279(11):10784-95. doi: 10.1074/jbc.M313308200. Epub 2003 Dec 12.
62 Important roles of the AKR1C2 and SRD5A1 enzymes in progesterone metabolism in endometrial cancer model cell lines. Chem Biol Interact. 2015 Jun 5;234:297-308. doi: 10.1016/j.cbi.2014.11.012. Epub 2014 Nov 23.
63 Role of Human Aldo-Keto Reductases in the Metabolic Activation of the Carcinogenic Air Pollutant 3-Nitrobenzanthrone. Chem Res Toxicol. 2018 Nov 19;31(11):1277-1288. doi: 10.1021/acs.chemrestox.8b00250. Epub 2018 Nov 8.
64 New enzymatic assay for the AKR1C enzymes. Chem Biol Interact. 2013 Feb 25;202(1-3):204-9.
65 Aldo-keto reductase 1C3 expression in MCF-7 cells reveals roles in steroid hormone and prostaglandin metabolism that may explain its over-expression in breast cancer. J Steroid Biochem Mol Biol. 2010 Feb 15;118(3):177-87. doi: 10.1016/j.jsbmb.2009.12.009. Epub 2009 Dec 28.