Selective and potent inhibitors of human 20α-hydroxysteroid dehydrogenase (AKR1C1) that metabolizes neurosteroids derived from progesterone

Human 3α-hydroxysteroid dehydrogenase isoforms (AKR1C1–AKR1C4) of the aldo–keto reductase superfamily: functional plasticity and tissue distribution reveals roles in the inactivation and formation of male and female sex hormones

PENNING, T. M., BURCZYNSKI, M. E., JEZ, J. M., HUNG, C.-F., LIN, H.-K., MA, H., MOORE, M., PALACKAL, N., & RATNAM, K. (2000) · Biochemical Journal · doi:10.1042/0264-6021:3510067 · Cited by 649 · see citing works

Human 3α-hydroxysteroid dehydrogenase isoforms (AKR1C1-AKR1C4) of the aldo-keto reductase superfamily: functional plasticity and tissue distribution reveals roles in the inactivation and formation of male and female sex hormones

PENNING, T. M., BURCZYNSKI, M. E., JEZ, J. M., HUNG, C.-F., LIN, H.-K., MA, H., MOORE, M., PALACKAL, N., & RATNAM, K. (2000) · Biochemical Journal · doi:10.1042/bj3510067 · Cited by 649 · see citing works

Neuroactive steroids: mechanisms of action and neuropsychopharmacological perspectives

Rupprecht, R., & Holsboer, F. (1999) · Trends in Neurosciences · doi:10.1016/s0166-2236(99)01399-5 · Cited by 636 · see citing works

GABAA receptor α4 subunit suppression prevents withdrawal properties of an endogenous steroid

Smith, S. S., Gong, Q. H., Hsu, F.-C., Markowitz, R. S., ffrench-Mullen, J. M. H., & Li, X. (1998) · Nature · doi:10.1038/31948 · Cited by 564 · see citing works

Neurosteroid metabolism in the human brain

Stoffel‐Wagner, B. (2001) · European Journal of Endocrinology · doi:10.1530/eje.0.1450669 · Cited by 537 · see citing works

Principles of enzyme kinetics

Cornish-Bowden, A. J. (1976) · Cited by 459 · see citing works

Principles of Enzyme Kinetics

(1976) · Elsevier eBooks · doi:10.1016/c2013-0-04221-1 · Cited by 297 · see citing works

The aldo-keto reductase (AKR) superfamily: an update

Jez, J. M., & Penning, T. M. (2001) · Chemico-Biological Interactions · doi:10.1016/s0009-2797(00)00295-7 · Cited by 239 · see citing works

Expression and Characterization of Recombinant Type 2 3α-Hydroxysteroid Dehydrogenase (HSD) from Human Prostate: Demonstration of Bifunctional 3α/17β-HSD Activity and Cellular Distribution

Lin, H.-K., Jez, J. M., Schlegel, B. P., Peehl, D. M., Pachter, J. A., & Penning, T. M. (1997) · Molecular Endocrinology · doi:10.1210/mend.11.13.0026 · Cited by 194 · see citing works

Isoform-specific induction of a human aldo-keto reductase by polycyclic aromatic hydrocarbons (PAHs), electrophiles, and oxidative stress: implications for the alternative pathway of PAH activation catalyzed by human dihydrodiol dehydrogenase.

Burczynski, M. E., Hseuh-Kung, L. I. N., & Penning, T. M. (1999) · PubMed · Cited by 189 · see citing works

Substrate specificity, gene structure and tissue-specific distribution of multiple human 3α-hydroxysteroid dehydrogenases

Khanna, M., Qin, K.-N., Wang, R. W., & Cheng, K.-C. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.34.20162 · Cited by 174 · see citing works

Identification of a Principal mRNA Species for Human 3 -Hydroxysteroid Dehydrogenase Isoform (AKR1C3) That Exhibits High Prostaglandin D2 11-Ketoreductase Activity

Matsuura, K., Shiraishi, H., Hara, A., Sato, K., Deyashiki, Y., Ninomiya, M., & Sakai, S. (1998) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a022211 · Cited by 172 · see citing works

Enzymology and Molecular Biology of Carbonyl Metabolism 7

Weiner, H., Maser, E., Crabb, D. W., & Lindahl, R. G. (1999) · Advances in experimental medicine and biology · doi:10.1007/978-1-4615-4735-8 · Cited by 127 · see citing works

Relationship of human liver dihydrodiol dehydrogenases to hepatic bile-acid-binding protein and an oxidoreductase of human colon cells

Hara, A., Matsuura, K., Tamada, Y., Sato, K., Miyabe, Y., Deyashiki, Y., & ISHIDA, N. (1996) · Biochemical Journal · doi:10.1042/bj3130373 · Cited by 109 · see citing works

Characterization of a human 20alpha-hydroxysteroid dehydrogenase

Zhang, Y., Dufort, I., Rheault, P., & Luu-The, V. (2000) · Journal of Molecular Endocrinology · doi:10.1677/jme.0.0250221 · Cited by 109 · see citing works

Neurosteroids A New Regulatory Function in the Nervous System

(2000) · Clinical Endocrinology · doi:10.1046/j.1365-2265.2000.01084.x · Cited by 107 · see citing works

Crystal Structure of Human Type III 3α-Hydroxysteroid Dehydrogenase/Bile Acid Binding Protein Complexed with NADP+ and Ursodeoxycholate,

Jin, Y., Stayrook, S. E., Albert, R. H., Palackal, N. T., Penning, T. M., & Lewis, M. (2001) · Biochemistry · doi:10.1021/bi010919a · Cited by 99 · see citing works

Neurosteroids: A New Regulatory Function in the Nervous System

Ross, L. E., & Sellers, E. M. (1999) · Behavioural Neurology · doi:10.1155/1999/308037 · Cited by 75 · see citing works

Substrate Specificity of Human 3(20).ALPHA.-Hydroxysteroid Dehydrogenase for Neurosteroids and Its Inhibition by Benzodiazepines.

Usami, N., Yamamoto, T., Shintani, S., Higaki, Y., Ishikura, S., Patagiri, Y., & Hara, A. (2002) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.25.441 · Cited by 59 · see citing works

Sequence of the cDNA of a human dihydrodiol dehydrogenase isoform (AKR1C2) and tissue distribution of its mRNA

Shiraishi, H., Ishikura, S., Matsuura, K., Deyashiki, Y., Ninomiya, M., Sakai, S., & Hara, A. (1998) · Biochemical Journal · doi:10.1042/bj3340399 · Cited by 45 · see citing works

Identification of amino acid residues responsible for differences in substrate specificity and inhibitor sensitivity between two human liver dihydrodiol dehydrogenase isoenzymes by site-directed mutagenesis

Matsuura, K., Deyashiki, Y., Sato, K., ISHIDA, N., Miwa, G., & Hara, A. (1997) · Biochemical Journal · doi:10.1042/bj3230061 · Cited by 42 · see citing works

Roles of the C-terminal domains of human dihydrodiol dehydrogenase isoforms in the binding of substrates and modulators: probing with chimaeric enzymes

Matsuura, K., Hara, A., Deyashiki, Y., Iwasa, H., Kume, T., Ishikura, S., Shiraishi, H., & Katagiri, Y. (1998) · Biochemical Journal · doi:10.1042/bj3360429 · Cited by 40 · see citing works

The Selective Interaction of Neurosteroids with the GABAA Receptor

Lambert, J. J., Belelli, D., Shepherd, S., Pistis, M., & Peters, J. A. (1999) · Humana Press eBooks · doi:10.1007/978-1-59259-693-5_7 · Cited by 36 · see citing works

Messenger RNA of steroid 21-hydroxylase (CYP21) is expressed in the human hippocampus

Beyenburg, S., Watzka, M., Clusmann, H., Blümcke, I., BIDLINGMAIER, F., Elger, C. E., & Stoffel‐Wagner, B. (2001) · Neuroscience Letters · doi:10.1016/s0304-3940(01)01991-7 · Cited by 33 · see citing works

Expression and Kinetic Properties of a Recombinant 3α-Hydroxysteroid/Dihydrodiol Dehydrogenase Isoenzyme of Human Liver

Deyashiki, Y., Tamada, Y., Miyabe, Y., Nakanishi, M., Matsuura, K., & Hara, A. (1995) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a124904 · Cited by 32 · see citing works

Aspects of Hormonal Steroid Metabolism in the Nervous System

Poletti, A., Celotti, F., Maggi, R., Melcangi, R. C., Martini, L., & Negri‐Cesi, P. (1999) · Humana Press eBooks · doi:10.1007/978-1-59259-693-5_6 · Cited by 13 · see citing works

Expression of mRNAs for dihydrodiol dehydrogenase isoforms in human tissues.

Shiraishi, H., Matsuura, K., Kume, T., & Hara, A. (1999) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4615-4735-8_68 · Cited by 13 · see citing works

Kinetic Studies of the Inhibition of a Human Liver 3.ALPHA.-Hydroxysteroid/Dihydrodiol Dehydrogenase Isozyme by Bile Acids and Anti-inflammatory Drugs.

Miyabe, Y., Amano, T., Deyashiki, Y., Hara, A., & Tsukada, F. (1995) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.18.9 · Cited by 7 · see citing works

The Aldo-Keto Reductase Superfamily and its Role in Drug Metabolism and Detoxification

Barski, O. A., Tipparaju, S. M., & Bhatnagar, A. (2008) · Drug Metabolism Reviews · doi:10.1080/03602530802431439 · Cited by 543 · see citing works

Human Cytosolic 3α-Hydroxysteroid Dehydrogenases of the Aldo-keto Reductase Superfamily Display Significant 3β-Hydroxysteroid Dehydrogenase Activity

Steckelbroeck, S., Jin, Y., Gopishetty, S., Oyesanmi, B., & Penning, T. M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313308200 · Cited by 270 · see citing works

Carbonyl Reductases and Pluripotent Hydroxysteroid Dehydrogenases of the Short-chain Dehydrogenase/reductase Superfamily

Hoffmann, F., & Maser, E. (2007) · Drug Metabolism Reviews · doi:10.1080/03602530600969440 · Cited by 220 · see citing works

Role of aldo-keto reductase family 1 (AKR1) enzymes in human steroid metabolism

Rižner, T. L., & Penning, T. M. (2014) · Steroids · doi:10.1016/j.steroids.2013.10.012 · Cited by 217 · see citing works

Alternative (backdoor) androgen production and masculinization in the human fetus

O’Shaughnessy, P. J., Antignac, J. P., Le Bizec, B., Morvan, M.-L., Svechnikov, K., Söder, O., Savchuk, I., Monteiro, A., Soffientini, U., Johnston, Z. C., et al. (2019) · PLOS Biology · doi:10.1371/journal.pbio.3000002 · Cited by 177 · see citing works

Multiplicity of Mammalian Reductases for Xenobiotic Carbonyl Compounds

Matsunaga, T., Shintani, S., & Hara, A. (2006) · Drug Metabolism and Pharmacokinetics · doi:10.2133/dmpk.21.1 · Cited by 148 · see citing works

AKR1C3 as a target in castrate resistant prostate cancer

Adeniji, A. O., Chen, M., & Penning, T. M. (2013) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2013.05.012 · Cited by 143 · see citing works

Inhibitors of type 5 17β-hydroxysteroid dehydrogenase (AKR1C3): Overview and structural insights

Byrns, M. C., Jin, Y., & Penning, T. M. (2010) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2010.11.004 · Cited by 144 · see citing works

Aldo–Keto Reductase AKR1C1–AKR1C4: Functions, Regulation, and Intervention for Anti-cancer Therapy

Zeng, C., Chang, L.-L., Ying, M., Cao, J., He, Q., Zhu, H., & Yang, B. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00119 · Cited by 138 · see citing works

Selective Loss of AKR1C1 and AKR1C2 in Breast Cancer and Their Potential Effect on Progesterone Signaling

Ji, Q., Aoyama, C., Nien, Y.-D., Liu, P. I., Chen, P. K., Chang, L., Stanczyk, F. Z., & Stolz, A. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-1608 · Cited by 119 · see citing works

Kinetic studies of AKR1B10, human aldose reductase-like protein: Endogenous substrates and inhibition by steroids

Endo, S., Matsunaga, T., Mamiya, H., Ohta, C., Soda, M., Kitade, Y., Tajima, K., Zhao, H.-T., El-Kabbani, O. A. L., & Hara, A. (2009) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2009.05.009 · Cited by 108 · see citing works

Selectivity and potency of the retroprogesterone dydrogesterone in vitro

Rižner, T. L., Brožič, P., Doucette, C., Turek-Etienne, T. C., Müller‐Vieira, U., Sonneveld, E., van der Burg, B., Böcker, C., & Husen, B. (2011) · Steroids · doi:10.1016/j.steroids.2011.02.043 · Cited by 89 · see citing works

Carbonyl reduction pathways in drug metabolism

Malátková, P., & Wsól, V. (2013) · Drug Metabolism Reviews · doi:10.3109/03602532.2013.853078 · Cited by 84 · see citing works

Characterization of Human Liver Enzymes Involved in the Biotransformation of Boceprevir, a Hepatitis C Virus Protease Inhibitor

Ghosal, A., Yuan, Y., Tong, W., Su, A.-D., Gu, C., Chowdhury, S. K., Kishnani, N. S., & Alton, K. B. (2010) · Drug Metabolism and Disposition · doi:10.1124/dmd.110.036996 · Cited by 68 · see citing works

Environmental Pollutants and Hydroxysteroid Dehydrogenases

Ye, L., Guo, J., & Ge, R. (2014) · Vitamins and hormones · doi:10.1016/b978-0-12-800095-3.00013-4 · Cited by 67 · see citing works

Tibolone Metabolism in Human Liver Is Catalyzed by 3α/3β-Hydroxysteroid Dehydrogenase Activities of the Four Isoforms of the Aldo-Keto Reductase (AKR)1C Subfamily

Steckelbroeck, S., Oyesanmi, B., Jin, Y., Lee, S. H., Kloosterboer, H. J., & Penning, T. M. (2006) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.105.091587 · Cited by 66 · see citing works

Steroids and Alzheimer’s Disease: Changes Associated with Pathology and Therapeutic Potential

Akwa, Y. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21134812 · Cited by 63 · see citing works

Development of Novel AKR1C3 Inhibitors as New Potential Treatment for Castration-Resistant Prostate Cancer

Endo, S., Oguri, H., Segawa, J., Kawai, M., Hu, D., Xia, S., Okada, T., Irie, K., Fujii, S., Gouda, H., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00939 · Cited by 63 · see citing works

Aldo-Keto Reductase Family 1 Member B10 Inhibitors: Potential Drugs for Cancer Treatment

Huang, L., He, R., Luo, W., Zhu, Y., Li, J., Tan, T., Zhang, X., Hu, Z., & Luo, D. (2016) · Recent Patents on Anti-Cancer Drug Discovery · doi:10.2174/1574892811888160304113346 · Cited by 60 · see citing works

Selective Inhibition of the Tumor Marker AKR1B10 by Antiinflammatory N-Phenylanthranilic Acids and Glycyrrhetic Acid

Endo, S., Matsunaga, T., Soda, M., Tajima, K., Zhao, H.-T., El-Kabbani, O. A. L., & Hara, A. (2010) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.33.886 · Cited by 54 · see citing works

Cross-Kingdom Actions of Phytohormones: A Functional Scaffold Exploration

Lin, L., & Tan, R. X. (2011) · Chemical Reviews · doi:10.1021/cr100061j · Cited by 53 · see citing works

Two pathways for prostaglandin F2α synthesis by the primate periovulatory follicle

Dozier, B. L., Watanabe, K., & Duffy, D. M. (2008) · Reproduction · doi:10.1530/rep-07-0514 · Cited by 53 · see citing works

Aldo-keto reductase 1C3—Assessment as a new target for the treatment of endometriosis

Rižner, T. L., & Penning, T. M. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.104446 · Cited by 51 · see citing works

Corticosterone Transfer and Metabolism in the Dually Perfused Rat Placenta: Effect of 11β-hydroxysteroid Dehydrogenase Type 2

Štaud, F., Mazancová, K., Mikšı́k, I., Pávek, P., Fendrich, Z., & Pácha, J. (2005) · Placenta · doi:10.1016/j.placenta.2005.01.001 · Cited by 50 · see citing works

Stereospecific reduction of 5β-reduced steroids by human ketosteroid reductases of the AKR (aldo–keto reductase) superfamily: role of AKR1C1-AKR1C4 in the metabolism of testosterone and progesterone via the 5β-reductase pathway

Jin, Y., Mesaros, A. C., Blair, I. A., & Penning, T. M. (2011) · Biochemical Journal · doi:10.1042/bj20101804 · Cited by 49 · see citing works

Selective Inhibition of Human Type-5 17β-Hydroxysteroid Dehydrogenase (AKR1C3) by Baccharin, a Component of Brazilian Propolis

Endo, S., Matsunaga, T., Kanamori, A., Otsuji, Y., Nagai, H., Sundaram, K., El-Kabbani, O. A. L., Toyooka, N., Ohta, S., & Hara, A. (2012) · Journal of Natural Products · doi:10.1021/np201002x · Cited by 49 · see citing works

Aldo–keto reductases AKR1C1, AKR1C2 and AKR1C3 may enhance progesterone metabolism in ovarian endometriosis

Hevir, N., Vouk, K., Šinkovec, J., Ribič-Pucelj, M., & Lanišnik Rižner, T. (2011) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2011.01.003 · Cited by 48 · see citing works

Enzymes of the AKR1B and AKR1C Subfamilies and Uterine Diseases

Rižner, T. L. (2012) · Frontiers in Pharmacology · doi:10.3389/fphar.2012.00034 · Cited by 49 · see citing works

Synthesis of Potent and Selective Inhibitors of Aldo-Keto Reductase 1B10 and Their Efficacy against Proliferation, Metastasis, and Cisplatin Resistance of Lung Cancer Cells

Endo, S., Xia, S., Suyama, M., Morikawa, Y., Oguri, H., Hu, D., Ao, Y., Takahara, S., Horino, Y., Hayakawa, Y., et al. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b00830 · Cited by 48 · see citing works

Phytoestrogens as inhibitors of the human progesterone metabolizing enzyme AKR1C1

Brožič, P., Šmuc, T., Gobec, S., & Rižner, T. L. (2006) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2006.08.001 · Cited by 46 · see citing works

Nonsteroidal anti-inflammatory drugs and their analogues as inhibitors of aldo-keto reductase AKR1C3: New lead compounds for the development of anticancer agents

Gobec, S., Brožič, P., & Rižner, T. L. (2005) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2005.08.063 · Cited by 46 · see citing works

Significance of reductases in the detoxification of the tobacco-specific carcinogen NNK

Maser, E. (2004) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2004.03.001 · Cited by 42 · see citing works

Structure-Guided Design, Synthesis, and Evaluation of Salicylic Acid-Based Inhibitors Targeting a Selectivity Pocket in the Active Site of Human 20α-Hydroxysteroid Dehydrogenase (AKR1C1)

El-Kabbani, O. A. L., Scammells, P. J., Gosling, J., Dhagat, U., Endo, S., Matsunaga, T., Soda, M., & Hara, A. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm9001633 · Cited by 41 · see citing works

Inhibitors of human 20α-hydroxysteroid dehydrogenase (AKR1C1)

El-Kabbani, O. A. L., Dhagat, U., & Hara, A. (2010) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2010.10.006 · Cited by 41 · see citing works

Important roles of the AKR1C2 and SRD5A1 enzymes in progesterone metabolism in endometrial cancer model cell lines

Sinreih, M., Anko, M., Zukunft, S., Adamski, J., & Rižner, T. L. (2014) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2014.11.012 · Cited by 40 · see citing works

Progestins as inhibitors of the human 20-ketosteroid reductases, AKR1C1 and AKR1C3

Beranič, N., Gobec, S., & Rižner, T. L. (2011) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2010.12.012 · Cited by 39 · see citing works

The Activity of SN33638, an Inhibitor of AKR1C3, on Testosterone and 17β-Estradiol Production and Function in Castration-Resistant Prostate Cancer and ER-Positive Breast Cancer

Yin, Y. D., Fu, M., Brooke, D. G., Heinrich, D. M., Denny, W. A., & Jamieson, S. M. F. (2014) · Frontiers in Oncology · doi:10.3389/fonc.2014.00159 · Cited by 33 · see citing works

Low Prolactin and High 20-α-Hydroxysteroid Dehydrogenase Levels Contribute to Lower Progesterone Levels in HIV-Infected Pregnant Women Exposed to Protease Inhibitor–Based Combination Antiretroviral Therapy

Papp, E., Balogun, K. A., Banko, N. S., Mohammadi, H., Loutfy, M. R., Yudin, M. H., Shah, R., MacGillivray, J., Murphy, K. E., Walmsley, S. L., et al. (2016) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiw004 · Cited by 31 · see citing works

Selectivity Determinants of Inhibitor Binding to Human 20α-Hydroxysteroid Dehydrogenase: Crystal Structure of the Enzyme in Ternary Complex with Coenzyme and the Potent Inhibitor 3,5-Dichlorosalicylic Acid

Dhagat, U., Endo, S., Sumii, R., Hara, A., & El-Kabbani, O. A. L. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm8003575 · Cited by 29 · see citing works

Up-Regulation of Carbonyl Reductase 1 Renders Development of Doxorubicin Resistance in Human Gastrointestinal Cancers

Matsunaga, T., Kezuka, C., Morikawa, Y., Suzuki, A., Endo, S., Iguchi, K., Miura, T., Nishinaka, T., Terada, T., El-Kabbani, O. A. L., et al. (2015) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b15-00176 · Cited by 26 · see citing works

Enhanced 4-Hydroxynonenal Resistance inKEAP1Silenced Human Colon Cancer Cells

Jung, K.-A., & Kwak, M. (2013) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2013/423965 · Cited by 26 · see citing works

Overview of human 20 alpha-hydroxysteroid dehydrogenase (AKR1C1): Functions, regulation, and structural insights of inhibitors

Chu, X., He, S., Liu, Y., Liu, Y., Feng, F., Guo, Q., Zhao, L., & Sun, H. (2021) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2021.109746 · Cited by 26 · see citing works

Enzymatic characteristics of an aldo–keto reductase family protein (AKR1C15) and its localization in rat tissues

Endo, S., Matsunaga, T., Horie, K., Tajima, K., Bunai, Y., Carbone, V., El-Kabbani, O. A. L., & Hara, A. (2007) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2007.05.008 · Cited by 23 · see citing works

Structure-based optimization and biological evaluation of human 20α-hydroxysteroid dehydrogenase (AKR1C1) salicylic acid-based inhibitors

El-Kabbani, O. A. L., Scammells, P. J., Day, T., Dhagat, U., Endo, S., Matsunaga, T., Soda, M., & Hara, A. (2010) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2010.08.052 · Cited by 21 · see citing works

Long-chain fatty acids inhibit human members of the aldo-keto reductase 1C subfamily

Hara, A., Endo, S., Matsunaga, T., Soda, M., Yashiro, K., & El-Kabbani, O. A. L. (2017) · The Journal of Biochemistry · doi:10.1093/jb/mvx041 · Cited by 20 · see citing works

Allopregnanolone: Metabolism, Mechanisms of Action, and Its Role in Cancer

Zamora-Sánchez, C. J., & Camacho‐Arroyo, I. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms24010560 · Cited by 18 · see citing works

Ruthenium complexes show potent inhibition of AKR1C1, AKR1C2, and AKR1C3 enzymes and anti-proliferative action against chemoresistant ovarian cancer cell line

Kljun, J., Pavlič, R., Hafner, E., Lipec, T., Silva, S. M., Tič, P., Turel, I., Büdefeld, T., Stojan, J., & Rižner, T. L. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.920379 · Cited by 18 · see citing works

Expression of human aldo–keto reductase 1C2 in cell lines of peritoneal endometriosis: potential implications in metabolism of progesterone and dydrogesterone and inhibition by progestins

Beranič, N., Brožič, P., Brus, B., Sosič, I., Gobec, S., & Rižner, T. L. (2012) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2011.12.011 · Cited by 16 · see citing works

Human 3-alpha hydroxysteroid dehydrogenase type 3 (3α-HSD3): The V54L mutation restricting the steroid alternative binding and enhancing the 20α-HSD activity

Zhang, B., Zhu, D., Hu, X., Zhou, M., Shang, P., & Lin, S. (2014) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2014.01.003 · Cited by 16 · see citing works

Porcine aldo-keto reductase 1C subfamily members AKR1C1 and AKR1C4: Substrate specificity, inhibitor sensitivity and activators

Endo, S., Morikawa, Y., Matsunaga, T., Hara, A., & Nishinaka, T. (2022) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2022.106113 · Cited by 16 · see citing works

Cloning and Characterization of Four Rabbit Aldo-Keto Reductases Featuring Broad Substrate Specificity for Xenobiotic and Endogenous Carbonyl Compounds: Relationship with Multiple Forms of Drug Ketone Reductases

Endo, S., Matsunaga, T., Arai, Y., Ikari, A., Tajima, K., El-Kabbani, O. A. L., Yamano, S., Hara, A., & Kitade, Y. (2014) · Drug Metabolism and Disposition · doi:10.1124/dmd.113.056044 · Cited by 15 · see citing works

Derivatives of pyrimidine, phthalimide and anthranilic acid as inhibitors of human hydroxysteroid dehydrogenase AKR1C1

Brožič, P., Cesar, J., Kovač, A., Davies, M., Johnson, A. P., Fishwick, C. W. G., Rižner, T. L., & Gobec, S. (2008) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2008.10.019 · Cited by 16 · see citing works

9,10-Phenanthrenequinone promotes secretion of pulmonary aldo-keto reductases with surfactant

Matsunaga, T., Haga, M., Watanabe, G., Shinoda, Y., Endo, S., Kajiwara, Y., Tanaka, H., Inagaki, N., El-Kabbani, O. A. L., & Hara, A. (2012) · Cell and Tissue Research · doi:10.1007/s00441-011-1304-5 · Cited by 14 · see citing works

Structure of aldehyde reductase in ternary complex with coenzyme and the potent 20α-hydroxysteroid dehydrogenase inhibitor 3,5-dichlorosalicylic acid: Implications for inhibitor binding and selectivity

Carbone, V., Chung, R. P. ‐., Endo, S., Hara, A., & El-Kabbani, O. A. L. (2008) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2008.08.014 · Cited by 14 · see citing works

Localization and altered expression of AKR1C family members in human ovarian tissues

Ji, Q., Aoyama, C., Chen, P. K., Stolz, A., & Liu, P. (2005) · Molecular and Cellular Probes · doi:10.1016/j.mcp.2005.03.003 · Cited by 13 · see citing works

Nrf2 in Host Defense: Over the Rainbow

Cho, H., Kwak, M., & Pi, J. (2013) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2013/975839 · Cited by 13 · see citing works

AKR1C1 protects against intracerebral hemorrhage by suppressing neuronal cell death via the P53/SLC7A11/GPX4 axis

Yang, Q., Wang, C., Cao, J., Tang, Z., & Duan, S. (2025) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2025.111254 · Cited by 12 · see citing works

Probing the inhibitor selectivity pocket of human 20α-hydroxysteroid dehydrogenase (AKR1C1) with X-ray crystallography and site-directed mutagenesis

El-Kabbani, O. A. L., Dhagat, U., Soda, M., Endo, S., Matsunaga, T., & Hara, A. (2011) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2011.01.076 · Cited by 12 · see citing works

Reductive metabolism of nabumetone by human liver microsomal and cytosolic fractions: exploratory prediction using inhibitors and substrates as marker probes

Matsumoto, K., Hasegawa, T., Kamei, T., Koyanagi, J., Takahashi, T., Akimoto, M., & Sugibayashi, K. (2014) · European Journal of Drug Metabolism and Pharmacokinetics · doi:10.1007/s13318-014-0190-0 · Cited by 12 · see citing works

The role of neuroactive steroids in psychiatric and neurological disorders: Neurobiology and therapeutic perspectives

Pinna, G., & Bortolato, M. (2025) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2025.106438 · Cited by 11 · see citing works

2,3-Diarylpropenoic acids as selective non-steroidal inhibitors of type-5 17β-hydroxysteroid dehydrogenase (AKR1C3)

Gazvoda, M., Beranič, N., Turk, S., Burja, B., Kočevar, M., Rižner, T. L., Gobec, S., & Polanc, S. (2013) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2012.12.045 · Cited by 11 · see citing works

Discovery of new inhibitors of aldo-keto reductase 1C1 by structure-based virtual screening

Brožič, P., Turk, S., Rižner, T. L., & Gobec, S. (2008) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2008.08.002 · Cited by 11 · see citing works

The prognosis of lipid reprogramming with the HMG-CoA reductase inhibitor, rosuvastatin, in castrated Egyptian prostate cancer patients: Randomized trial

Karkeet, R. M., Zekri, A. N., Sayed‐Ahmed, M. M., Sherif, G. M., Salem, S., Abdelbary, A., Fouad, M. A., & Saad, S. Y. (2022) · PLoS ONE · doi:10.1371/journal.pone.0278282 · Cited by 10 · see citing works

Characterization of rabbit morphine 6-dehydrogenase and two NAD+-dependent 3α(17β)-hydroxysteroid dehydrogenases

Endo, S., Matsunaga, T., Fujimoto, A., Kumada, S., Arai, Y., Miura, Y., Mikamo, H., El-Kabbani, O. A. L., Yamano, S., Iinuma, M., et al. (2012) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2012.11.013 · Cited by 10 · see citing works

Aldo-Keto Reductases as New Therapeutic Targets for Colon Cancer Chemoresistance

Matsunaga, T., El-Kabbani, O. A. L., & Hara, A. (2013) · Resistance to targeted anti-cancer therapeutics · doi:10.1007/978-1-4614-7070-0_6 · Cited by 10 · see citing works

The Combination of Metyrapone and Oxazepam for the Treatment of Cocaine and Other Drug Addictions

Goeders, N. E., Guerin, G. F., & Schmoutz, C. D. (2014) · Advances in pharmacology · doi:10.1016/b978-0-12-420118-7.00011-1 · Cited by 10 · see citing works

Aldo-keto reductase family 1 member C1 regulates the osteogenic differentiation of human ASCs by targeting the progesterone receptor

Liu, X., Lian, X., Liu, X., Du, Y., Zhu, Y., Hu, M., Zhang, P., Liu, Y., & Zhou, Y. (2021) · Stem Cell Research & Therapy · doi:10.1186/s13287-021-02425-3 · Cited by 9 · see citing works

New enzymatic assay for the AKR1C enzymes

Beranič, N., Štefane, B., Brus, B., Gobec, S., & Rižner, T. L. (2012) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2012.12.003 · Cited by 10 · see citing works

Pharmacogenetics of aldo-keto reductase 1C (AKR1C) enzymes

Alshogran, O. Y. (2017) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2017.1376648 · Cited by 9 · see citing works

Synthesis, Enzyme Localization, and Regulation of Neurosteroids

Smith, S. S. (2003) · CRC Press eBooks · doi:10.1201/9780203508169.ch1 · Cited by 9 · see citing works

Non-stereo-selective cytosolic human brain tissue 3-ketosteroid reductase is refractory to inhibition by AKR1C inhibitors

Steckelbroeck, S., Lütjohann, D., Bauman, D. R., Ludwig, M. Z., Friedl, A., Hans, V., Penning, T. M., & Klingmüller, D. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2010.07.005 · Cited by 8 · see citing works

Rabbit 3-hydroxyhexobarbital dehydrogenase is a NADPH-preferring reductase with broad substrate specificity for ketosteroids, prostaglandin D2, and other endogenous and xenobiotic carbonyl compounds

Endo, S., Matsunaga, T., Matsumoto, A., Arai, Y., Ohno, S., El-Kabbani, O. A. L., Tajima, K., Bunai, Y., Yamano, S., Hara, A., et al. (2013) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.08.024 · Cited by 7 · see citing works

Substrate Specificity and Inhibitor Sensitivity of Rabbit 20α-Hydroxysteroid Dehydrogenase

Endo, S., Arai, Y., Hara, A., Kitade, Y., Bunai, Y., El-Kabbani, O. A. L., & Matsunaga, T. (2013) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b13-00342 · Cited by 6 · see citing works

Design and development of novel inhibitors of aldo-ketoreductase 1C1 as potential lead molecules in treatment of breast cancer

Verma, P., Hassan, M. I., Singh, A. K., & Singh, I. K. (2021) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-021-04134-0 · Cited by 6 · see citing works

Genetic and computational analysis of AKR1C4 gene rs17134592 polymorphism in breast cancer among the Bangladeshi population

Shaon, M. A., Ansari, F., Mahmud, Z., Tamanna, S., Saba, A. A., Sikder, R., Howlader, T., & Howlader, M. Z. H. (2025) · Scientific Reports · doi:10.1038/s41598-025-13411-7 · Cited by 6 · see citing works

Factorizing the role of a critical leucine residue in the binding of substrate to human 20α-hydroxysteroid dehydrogenase (AKR1C1): Molecular modeling and kinetic studies of the Leu308Val mutant enzyme

Dhagat, U., Endo, S., Soda, M., Hara, A., & El-Kabbani, O. A. L. (2010) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2010.06.137 · Cited by 5 · see citing works

Mouse Akr1cl gene product is a prostaglandin D2 11-ketoreductase with strict substrate specificity

Endo, S., Matsunaga, T., & Hara, A. (2019) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2019.108096 · Cited by 4 · see citing works

Involvement of porcine and human carbonyl reductases in the metabolism of epiandrosterone, 11-oxygenated steroids, neurosteroids, and corticosteroids

Endo, S., Morikawa, Y., Suenami, K., Sakai, Y., Abe, N., Matsunaga, T., Hara, A., & Takasu, M. (2024) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2024.106574 · Cited by 3 · see citing works

New inhibitors of fungal 17β-hydroxysteroid dehydrogenase based on the [1,5]-benzodiazepine scaffold

Živec, M., Sova, M., Brunskole, M., Lenaršič, R., Rižner, T. L., & Gobec, S. (2007) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756360600953819 · Cited by 3 · see citing works

Stereoselective synthesis of allopregnanolone catalyzed by ketoreductase

Hou, Y., Lv, J., Guo, Y., Fang, J., Huang, C., Zhang, W., Jia, X., You, S., & Qin, B. Y. (2023) · Molecular Catalysis · doi:10.1016/j.mcat.2023.113433 · Cited by 2 · see citing works

AKR1C4 regulates the sensitivity of colorectal cancer cells to chemotherapy through ferroptosis modulation

Wang, L., Lv, C., & Liu, X. (2024) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-024-04685-1 · Cited by 2 · see citing works

Identification of Anti‐Cancer Agents Targeting Aldo‐Keto Reductase (AKR) 1C3 Protein by Pharmacophore Modeling, Virtual Screening and Molecular Docking

Khalilullah, H. (2021) · ChemistrySelect · doi:10.1002/slct.202103151 · Cited by 2 · see citing works

Several distinct enzymes catalyze 20α-hydroxysteroid dehydrogenase activity in mouse liver and kidney

Imamura, Y., Ohtaguro, M., & Shimada, H. (2007) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2007.02.010 · Cited by 2 · see citing works

Brain Metabolism of Allopregnanolone and Isoallopregnanolone in Male Rat Brain

Öfverman, C., Hill, M., Johansson, M., & Bäckström, T. C. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26178559 · Cited by 1 · see citing works

Canine aldo-keto reductase 1C3 (AKR1C3/PGFS) exhibits 17β/20α-hydroxysteroid dehydrogenase activity and is inhibited by trilostane

Endo, S., Hayashi, R., Nakada, Y., Kudo, Y., Morikawa, Y., Sakai, Y., Suenami, K., Abe, N., Matsunaga, T., Hara, A., et al. (2025) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2025.106874 · Cited by 1 · see citing works

Ketone reduction drives major circulating metabolites of GDC-8264 in humans

Wang, S., Wong, S., DiPasquale, A. G., Ma, S., Hong, A. Y., Mulder, T., Wong, S., Aguirre, A. L., Chua, C., Chen, L., et al. (2026) · Drug Metabolism and Disposition · doi:10.1016/j.dmd.2026.100278 · Cited by 1 · see citing works

Asymmetric Bio- and Chemoreduction of 2-Benzylidenecyclopentanone Derivatives

Štefane, B., Grošelj, U., Svete, J., & Požgan, F. (2017) · Acta chimica slovenica · doi:10.17344/acsi.2017.3543 · Cited by 1 · see citing works

Structure and biological function of human 3-alpha hydroxysteroid dehydrogenase type 3 in breast cancer

Zhang, B. (2014) · Corpus Université Laval (Université Laval)

AKR1C inhibitors medroxyprogesterone acetate and mefenamic acid exhibit antitumor activity alone and combined with carboplatin in platinum-resistant high-grade serous ovarian cancer models

Marolt, N., Zottel, A., Annibali, D., Amant, F. C., & Rižner, T. L. (2026) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2026.119079

BindingDB Entry 50037633: Nonsteroidal anti-inflammatory drugs and their analogues as inhibitors of aldo-keto reductase AKR1C3: new lead compounds for the development of anticancer agents.

BindingDB (2012) · UC San Diego · doi:10.7270/q27d2vx4

BindingDB Entry 50000163: Synthesis of Potent and Selective Inhibitors of Aldo-Keto Reductase 1B10 and Their Efficacy against Proliferation, Metastasis, and Cisplatin Resistance of Lung Cancer Cells.

BindingDB (2019) · UC San Diego · doi:10.7270/q2nz89s7

BindingDB Entry 50032522: Structure-based optimization and biological evaluation of human 20a-hydroxysteroid dehydrogenase (AKR1C1) salicylic acid-based inhibitors.

BindingDB (2011) · UC San Diego · doi:10.7270/q2r78ff3

BindingDB Entry 50042683: 2,3-diarylpropenoic acids as selective non-steroidal inhibitors of type-5 17ß-hydroxysteroid dehydrogenase (AKR1C3).

BindingDB (2013) · UC San Diego · doi:10.7270/q2br8th0

BindingDB Entry 50004514: Probing the inhibitor selectivity pocket of human 20α-hydroxysteroid dehydrogenase (AKR1C1) with X-ray crystallography and site-directed mutagenesis.

BindingDB (2020) · UC San Diego · doi:10.7270/q20g3nz0

BindingDB Entry 50039838: Selective inhibition of human type-5 17ß-hydroxysteroid dehydrogenase (AKR1C3) by baccharin, a component of Brazilian propolis.

BindingDB (2013) · UC San Diego · doi:10.7270/q2z320p2

BindingDB Entry 2949: Selectivity determinants of inhibitor binding to human 20alpha-hydroxysteroid dehydrogenase: crystal structure of the enzyme in ternary complex with coenzyme and the potent inhibitor 3,5-dichlorosalicylic acid.

BindingDB (2009) · UC San Diego · doi:10.7270/q2mg7mtw

BindingDB Entry 50028683: Structure-guided design, synthesis, and evaluation of salicylic acid-based inhibitors targeting a selectivity pocket in the active site of human 20alpha-hydroxysteroid dehydrogenase (AKR1C1).

BindingDB (2010) · UC San Diego · doi:10.7270/q2765f6t

BindingDB Entry 50010918: Development of Novel AKR1C3 Inhibitors as New Potential Treatment for Castration-Resistant Prostate Cancer.

BindingDB (2021) · UC San Diego · doi:10.7270/q2v40zsn

Substrate Specificity of Human 3(20).ALPHA.-Hydroxysteroid Dehydrogenase for Neurosteroids and Its Inhibition by Benzodiazepines.

Usami, N., Yamamoto, T., Shintani, S., Higaki, Y., Ishikura, S., Patagiri, Y., & Hara, A. (2002) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.25.441 · Cited by 59 · see citing works

Non-stereo-selective cytosolic human brain tissue 3-ketosteroid reductase is refractory to inhibition by AKR1C inhibitors

Steckelbroeck, S., Lütjohann, D., Bauman, D. R., Ludwig, M. Z., Friedl, A., Hans, V., Penning, T. M., & Klingmüller, D. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2010.07.005 · Cited by 8 · see citing works

Derivatives of pyrimidine, phthalimide and anthranilic acid as inhibitors of human hydroxysteroid dehydrogenase AKR1C1

Brožič, P., Cesar, J., Kovač, A., Davies, M., Johnson, A. P., Fishwick, C. W. G., Rižner, T. L., & Gobec, S. (2008) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2008.10.019 · Cited by 16 · see citing works

2,3-Diarylpropenoic acids as selective non-steroidal inhibitors of type-5 17β-hydroxysteroid dehydrogenase (AKR1C3)

Gazvoda, M., Beranič, N., Turk, S., Burja, B., Kočevar, M., Rižner, T. L., Gobec, S., & Polanc, S. (2013) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2012.12.045 · Cited by 11 · see citing works

Inhibitors of Aldo-Keto Reductases AKR1C1-AKR1C4

Brožič, P., Turk, S., Rižner, T. L., & Gobec, S. (2011) · Current Medicinal Chemistry · doi:10.2174/092986711795933713 · Cited by 44 · see citing works