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AKR1C3与疾病的关系
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Abstract:
醛酮还原酶家族1成员C3 (AKR1C3)，也被称为5型17β羟基类固醇脱氢酶(17β-HSD5)或前列腺素F (PGF)合成酶，在雄激素生物合成中起关键作用。它催化弱雄激素、雌酮(弱雌激素)和PGD2分别转化为强雄激素(睾酮和5α-二氢睾酮)、17β-雌二醇(强雌激素)和11β-PGF2α。AKR1C3水平升高激活雄激素受体(AR) 8信号通路，促进肿瘤复发和对癌症治疗产生耐药性。AKR1C3的过表达作为一种致癌因子，促进癌细胞的增殖、侵袭和转移，并与癌症患者的不良预后和总生存期相关。抑制AKR1C3已被证明在抑制肿瘤进展和克服治疗耐药性方面具有强大的功效。因此，AKR1C3抑制剂的开发和设计引起了研究人员越来越多的兴趣，近年来取得了重大进展。本文简要介绍了AKR1C3的生理和病理功能，并对近年来选择性AKR1C3抑制剂的研究进展进行了综述。我们的目的是为未来的药物发现和潜在的治疗前景提供参考，新的、有效的、选择性的AKR1C3抑制剂。
Aldo-Keto Reductase Family 1 Member C3 (AKR1C3), also known as type 5 17β-hydroxysteroid dehydrogenase (17β-HSD5) or prostaglandin F (PGF) synthase, functions as a pivotal enzyme in androgen biosynthesis. It catalyzes the conversion of weak androgens, estrone (a weak estrogen), and PGD2 into potent androgens (testosterone and 5α-dihydrotestosterone), 17β-estradiol (a potent estrogen), and 11β-PGF2α, respectively. Elevated levels of AKR1C3 activate androgen receptor (AR) signaling pathway, contributing to tumor recurrence and imparting resistance to cancer therapies. The overexpression of AKR1C3 serves as an oncogenic factor, promoting carcinoma cell proliferation, invasion, and metastasis, and is correlated with unfavorable prognosis and overall survival in carcinoma patients. Inhibiting AKR1C3 has demonstrated potent efficacy in suppressing tumor progression and overcoming treatment resistance. As a result, the development and design of AKR1C3 inhibitors have garnered increasing interest among researchers, with significant progress witnessed in recent years. Here, we briefly review the physiological and pathological function of AKR1C3 and then summarize the recent development of selective AKR1C3 inhibitors. We aim to provide a reference for future drug discovery and potential therapeutic perspectives on novel, potent, selective AKR1C3 inhibitors.
| [1] | Brožič, P., Turk, S., Adeniji, A.O., Konc, J., Janežič, D., Penning, T.M., et al. (2012) Selective Inhibitors of Aldo-Keto Reductases AKR1C1 and AKR1C3 Discovered by Virtual Screening of a Fragment Library. Journal of Medicinal Chemistry, 55, 7417-7424. https://doi.org/10.1021/jm300841n |
| [2] | Rižner, T.L. and Penning, T.M. (2020) Aldo-keto Reductase 1C3—Assessment as a New Target for the Treatment of Endometriosis. Pharmacological Research, 152, Article ID: 104446. https://doi.org/10.1016/j.phrs.2019.104446 |
| [3] | Penning, T.M. (2019) AKR1C3 (Type 5 17β-Hydroxysteroid Dehydrogenase/Prostaglandin F Synthase): Roles in Malignancy and Endocrine Disorders. Molecular and Cellular Endocrinology, 489, 82-91. https://doi.org/10.1016/j.mce.2018.07.002 |
| [4] | Yepuru, M., Wu, Z., Kulkarni, A., Yin, F., Barrett, C.M., Kim, J., et al. (2013) Steroidogenic Enzyme AKR1C3 Is a Novel Androgen Receptor-Selective Coactivator That Promotes Prostate Cancer Growth. Clinical Cancer Research, 19, 5613-5625. https://doi.org/10.1158/1078-0432.ccr-13-1151 |
| [5] | Zeng, C., Chang, L., Ying, M., Cao, J., He, Q., Zhu, H., et al. (2017) Aldo-Keto Reductase AKR1C1-AKR1C4: Functions, Regulation, and Intervention for Anti-Cancer Therapy. Frontiers in Pharmacology, 8, Article 119. https://doi.org/10.3389/fphar.2017.00119 |
| [6] | Penning, T.M., Steckelbroeck, S., Bauman, D.R., Miller, M.W., Jin, Y., Peehl, D.M., et al. (2006) Aldo-Keto Reductase (AKR) 1C3: Role in Prostate Disease and the Development of Specific Inhibitors. Molecular and Cellular Endocrinology, 248, 182-191. https://doi.org/10.1016/j.mce.2005.12.009 |
| [7] | Brawley, O.W. (2012) Prostate Cancer Epidemiology in the United States. World Journal of Urology, 30, 195-200. https://doi.org/10.1007/s00345-012-0824-2 |
| [8] | Jemal, A., Siegel, R., Xu, J. and Ward, E. (2010) Cancer Statistics, 2010. CA: A Cancer Journal for Clinicians, 60, 277-300. https://doi.org/10.3322/caac.20073 |
| [9] | Miyamoto, H., Messing, E.M. and Chang, C. (2004) Androgen Deprivation Therapy for Prostate Cancer: Current Status and Future Prospects. The Prostate, 61, 332-353. https://doi.org/10.1002/pros.20115 |
| [10] | Kirby, M., Hirst, C. and Crawford, E.D. (2011) Characterising the Castration-Resistant Prostate Cancer Population: A Systematic Review. International Journal of Clinical Practice, 65, 1180-1192. https://doi.org/10.1111/j.1742-1241.2011.02799.x |
| [11] | Wadosky, K.M. and Koochekpour, S. (2017) Androgen Receptor Splice Variants and Prostate Cancer: From Bench to Bedside. Oncotarget, 8, 18550-18576. https://doi.org/10.18632/oncotarget.14537 |
| [12] | Locke, J.A., Guns, E.S., Lubik, A.A., Adomat, H.H., Hendy, S.C., Wood, C.A., et al. (2008) Androgen Levels Increase by Intratumoral de Novo Steroidogenesis during Progression of Castration-Resistant Prostate Cancer. Cancer Research, 68, 6407-6415. https://doi.org/10.1158/0008-5472.can-07-5997 |
| [13] | Penning, T.M. (2014) Androgen Biosynthesis in Castration-Resistant Prostate Cancer. Endocrine-Related Cancer, 21, T67-T78. https://doi.org/10.1530/erc-14-0109 |
| [14] | Li, M., Zhang, L., Yu, J., Wang, X., Cheng, L., Ma, Z., et al. (2024) AKR1C3 in Carcinomas: From Multifaceted Roles to Therapeutic Strategies. Frontiers in Pharmacology, 15, Article 1378292. https://doi.org/10.3389/fphar.2024.1378292 |
| [15] | Liu, C., Lou, W., Zhu, Y., Yang, J.C., Nadiminty, N., Gaikwad, N.W., et al. (2015) Intracrine Androgens and AKR1C3 Activation Confer Resistance to Enzalutamide in Prostate Cancer. Cancer Research, 75, 1413-1422. https://doi.org/10.1158/0008-5472.can-14-3080 |
| [16] | Neuwirt, H., Bouchal, J., Kharaishvili, G., Ploner, C., Jöhrer, K., Pitterl, F., et al. (2020) Cancer-Associated Fibroblasts Promote Prostate Tumor Growth and Progression through Upregulation of Cholesterol and Steroid Biosynthesis. Cell Communication and Signaling, 18, Article No. 11. https://doi.org/10.1186/s12964-019-0505-5 |
| [17] | Wang, S., Yang, Q., Fung, K. and Lin, H. (2008) AKR1C2 and AKR1C3 Mediated Prostaglandin D2 Metabolism Augments the PI3K/Akt Proliferative Signaling Pathway in Human Prostate Cancer Cells. Molecular and Cellular Endocrinology, 289, 60-66. https://doi.org/10.1016/j.mce.2008.04.004 |
| [18] | Wang, B., Wu, S., Fang, Y., Sun, G., He, D., Hsieh, J., et al. (2020) The AKR1C3/AR‐V7 Complex Maintains CRPC Tumour Growth by Repressing B4GALT1 Expression. Journal of Cellular and Molecular Medicine, 24, 12032-12043. https://doi.org/10.1111/jcmm.15831 |
| [19] | Mozar, F., Sharma, V., Gorityala, S., Albert, J.M., Xu, Y. and Montano, M.M. (2021) Downregulation of Dihydrotestosterone and Estradiol Levels by HEXIM1. Endocrinology, 163, bqab236. https://doi.org/10.1210/endocr/bqab236 |
| [20] | Fan, L., Peng, G., Hussain, A., Fazli, L., Guns, E., Gleave, M., et al. (2015) The Steroidogenic Enzyme AKR1C3 Regulates Stability of the Ubiquitin Ligase Siah2 in Prostate Cancer Cells. Journal of Biological Chemistry, 290, 20865-20879. https://doi.org/10.1074/jbc.m115.662155 |
| [21] | Park, S., Song, C., Lin, C., Jiang, S., Osmulski, P.A., Wang, C., et al. (2020) Inhibitory Interplay of SULT2B1b Sulfotransferase with AKR1C3 Aldo-Keto Reductase in Prostate Cancer. Endocrinology, 161, bqz042. https://doi.org/10.1210/endocr/bqz042 |
| [22] | Thiery, J.P., Acloque, H., Huang, R.Y.J. and Nieto, M.A. (2009) Epithelial-Mesenchymal Transitions in Development and Disease. Cell, 139, 871-890. https://doi.org/10.1016/j.cell.2009.11.007 |
| [23] | Dozmorov, M.G., Azzarello, J.T., Wren, J.D., Fung, K., Yang, Q., Davis, J.S., et al. (2010) Elevated AKR1C3 Expression Promotes Prostate Cancer Cell Survival and Prostate Cell-Mediated Endothelial Cell Tube Formation: Implications for Prostate Cancer Progressioan. BMC Cancer, 10, Article No. 672. https://doi.org/10.1186/1471-2407-10-672 |
| [24] | Byrns, M.C., Jin, Y. and Penning, T.M. (2011) Inhibitors of Type 5 17β-Hydroxysteroid Dehydrogenase (AKR1C3): Overview and Structural Insights. The Journal of Steroid Biochemistry and Molecular Biology, 125, 95-104. https://doi.org/10.1016/j.jsbmb.2010.11.004 |
| [25] | Byrns, M.C. and Penning, T.M. (2009) Type 5 17β-Hydroxysteroid Dehydrogenase/Prostaglandin F Synthase (AKR1C3): Role in Breast Cancer and Inhibition by Non-Steroidal Anti-Inflammatory Drug Analogs. Chemico-Biological Interactions, 178, 221-227. https://doi.org/10.1016/j.cbi.2008.10.024 |
| [26] | Yoda, T., Kikuchi, K., Miki, Y., Onodera, Y., Hata, S., Takagi, K., et al. (2015) 11β-Prostaglandin F2α, a Bioactive Metabolite Catalyzed by AKR1C3, Stimulates Prostaglandin F Receptor and Induces Slug Expression in Breast Cancer. Molecular and Cellular Endocrinology, 413, 236-247. https://doi.org/10.1016/j.mce.2015.07.008 |
| [27] | Yin, Y.D., Fu, M., Brooke, D.G., Heinrich, D.M., Denny, W.A. and Jamieson, S.M.F. (2014) 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. Frontiers in Oncology, 4, Article 159. https://doi.org/10.3389/fonc.2014.00159 |
| [28] | Lewis, M.J., Wiebe, J.P. and Heathcote, J.G. (2004) Expression of Progesterone Metabolizing Enzyme Genes (AKR1C1, AKR1C2, AKR1C3, SRD5A1, SRD5A2) Is Altered in Human Breast Carcinoma. BMC Cancer, 4, Article No. 27. https://doi.org/10.1186/1471-2407-4-27 |
| [29] | Zhao, S., Wagn, S., Zhao, Z. and Li, W. (2019) AKR1C1-3, Notably AKR1C3, Are Distinct Biomarkers for Liver Cancer Diagnosis and Prognosis: Database Mining in Malignancies. Oncology Letters, 18, 4515-4522. https://doi.org/10.3892/ol.2019.10802 |
| [30] | Zhu, P., Feng, R., Lu, X., Liao, Y., Du, Z., Zhai, W., et al. (2021) Diagnostic and Prognostic Values of AKR1C3 and AKR1D1 in Hepatocellular Carcinoma. Aging, 13, 4138-4156. https://doi.org/10.18632/aging.202380 |
| [31] | Zhou, Q., Tian, W., Jiang, Z., Huang, T., Ge, C., Liu, T., et al. (2021) A Positive Feedback Loop of AKR1C3-Mediated Activation of NF-κB and STAT3 Facilitates Proliferation and Metastasis in Hepatocellular Carcinoma. Cancer Research, 81, 1361-1374. https://doi.org/10.1158/0008-5472.can-20-2480 |
| [32] | Pan, D., Yang, W., Zeng, Y., Qin, H., Xu, Y., Gui, Y., et al. (2022) AKR1C3 Regulated by NRF2/MAFG Complex Promotes Proliferation via Stabilizing PARP1 in Hepatocellular Carcinoma. Oncogene, 41, 3846-3858. https://doi.org/10.1038/s41388-022-02379-7 |
| [33] | Wu, C., Dai, C., Li, X., Sun, M., Chu, H., Xuan, Q., et al. (2022) AKR1C3-Dependent Lipid Droplet Formation Confers Hepatocellular Carcinoma Cell Adaptability to Targeted Therapy. Theranostics, 12, 7681-7698. https://doi.org/10.7150/thno.74974 |
| [34] | Chen, J., Zhang, J., Tian, W., Ge, C., Su, Y., Li, J., et al. (2023) AKR1C3 Suppresses Ferroptosis in Hepatocellular Carcinoma through Regulation of YAP/SLC7A11 Signaling Pathway. Molecular Carcinogenesis, 62, 833-844. https://doi.org/10.1002/mc.23527 |
| [35] | Garg, M., Nagata, Y., Kanojia, D., Mayakonda, A., Yoshida, K., Haridas Keloth, S., et al. (2015) Profiling of Somatic Mutations in Acute Myeloid Leukemia with FLT3-ITD at Diagnosis and Relapse. Blood, 126, 2491-2501. https://doi.org/10.1182/blood-2015-05-646240 |
| [36] | Short, N.J., Rytting, M.E. and Cortes, J.E. (2018) Acute Myeloid Leukaemia. The Lancet, 392, 593-606. https://doi.org/10.1016/s0140-6736(18)31041-9 |
| [37] | Morell, A., Čermáková, L., Novotná, E., Laštovičková, L., Haddad, M., Haddad, A., et al. (2020) Bruton’s Tyrosine Kinase Inhibitors Ibrutinib and Acalabrutinib Counteract Anthracycline Resistance in Cancer Cells Expressing AKR1C3. Cancers, 12, Article 3731. https://doi.org/10.3390/cancers12123731 |
| [38] | Wu, Z., Ou, J., Liu, N., Wang, Z., Chen, J., Cai, Z., et al. (2022) Upregulation of Tim‐3 Is Associated with Poor Prognosis in Acute Myeloid Leukemia. Cancer Medicine, 12, 8956-8969. https://doi.org/10.1002/cam4.5549 |
| [39] | Verma, K., Zang, T., Gupta, N., Penning, T.M. and Trippier, P.C. (2016) Selective AKR1C3 Inhibitors Potentiate Chemotherapeutic Activity in Multiple Acute Myeloid Leukemia (AML) Cell Lines. ACS Medicinal Chemistry Letters, 7, 774-779. https://doi.org/10.1021/acsmedchemlett.6b00163 |
| [40] | Penning, T.M., Jonnalagadda, S., Trippier, P.C. and Rižner, T.L. (2021) Aldo-keto Reductases and Cancer Drug Resistance. Pharmacological Reviews, 73, 1150-1171. https://doi.org/10.1124/pharmrev.120.000122 |
| [41] | Wang, Y., Liu, Y., Zhou, C., Wang, C., Zhang, N., Cao, D., et al. (2020) An AKR1C3-Specific Prodrug with Potent Anti-Tumor Activities against T-ALL. Leukemia & Lymphoma, 61, 1660-1668. https://doi.org/10.1080/10428194.2020.1728746 |
| [42] | He, P., Wang, C., Wang, Y., Wang, C., Zhou, C., Cao, D., et al. (2021) A Novel AKR1C3 Specific Prodrug TH3424 with Potent Antitumor Activity in Liver Cancer. Clinical Pharmacology & Therapeutics, 110, 229-237. https://doi.org/10.1002/cpt.2171 |
| [43] | Evans, K., Duan, J., Pritchard, T., Jones, C.D., McDermott, L., Gu, Z., et al. (2019) OBI-3424, a Novel AKR1C3-Activated Prodrug, Exhibits Potent Efficacy against Preclinical Models of T-ALL. Clinical Cancer Research, 25, 4493-4503. https://doi.org/10.1158/1078-0432.ccr-19-0551 |
| [44] | Reddi, D., Seaton, B.W., Woolston, D., Aicher, L., Monroe, L.D., Mao, Z.J., et al. (2022) AKR1C3 Expression in T Acute Lymphoblastic Leukemia/Lymphoma for Clinical Use as a Biomarker. Scientific Reports, 12, Article No. 5809. https://doi.org/10.1038/s41598-022-09697-6 |
| [45] | Moradi Manesh, D., El-Hoss, J., Evans, K., Richmond, J., Toscan, C.E., Bracken, L.S., et al. (2015) AKR1C3 Is a Biomarker of Sensitivity to PR-104 in Preclinical Models of T-Cell Acute Lymphoblastic Leukemia. Blood, 126, 1193-1202. https://doi.org/10.1182/blood-2014-12-618900 |
| [46] | Frycz, B.A., Murawa, D., Borejsza-Wysocki, M., Wichtowski, M., Spychała, A., Marciniak, R., et al. (2016) Transcript Level of AKR1C3 Is Down-Regulated in Gastric Cancer. Biochemistry and Cell Biology, 94, 138-146. https://doi.org/10.1139/bcb-2015-0096 |
| [47] | Li, Y., Tang, J., Li, J., Du, Y., Bai, F., Yang, L., et al. (2022) ARID3A Promotes the Chemosensitivity of Colon Cancer by Inhibiting AKR1C3. Cell Biology International, 46, 965-975. https://doi.org/10.1002/cbin.11789 |
| [48] | Kafka, M., Mayr, F., Temml, V., Möller, G., Adamski, J., Höfer, J., et al. (2020) Dual Inhibitory Action of a Novel AKR1C3 Inhibitor on Both Full-Length AR and the Variant AR-V7 in Enzalutamide Resistant Metastatic Castration Resistant Prostate Cancer. Cancers, 12, Article 2092. https://doi.org/10.3390/cancers12082092 |
| [49] | Zhao, J., Ning, S., Lou, W., Yang, J.C., Armstrong, C.M., Lombard, A.P., et al. (2020) Cross-Resistance among Next-Generation Antiandrogen Drugs through the AKR1C3/AR-V7 Axis in Advanced Prostate Cancer. Molecular Cancer Therapeutics, 19, 1708-1718. https://doi.org/10.1158/1535-7163.mct-20-0015 |
| [50] | Xu, D., Zhang, Y. and Jin, F. (2021) The Role of AKR1 Family in Tamoxifen Resistant Invasive Lobular Breast Cancer Based on Data Mining. BMC Cancer, 21, Article No. 1321. https://doi.org/10.1186/s12885-021-09040-8 |
| [51] | Zang, T., Verma, K., Chen, M., Jin, Y., Trippier, P.C. and Penning, T.M. (2015) Screening Baccharin Analogs as Selective Inhibitors against Type 5 17β-Hydroxysteroid Dehydrogenase (AKR1C3). Chemico-Biological Interactions, 234, 339-348. https://doi.org/10.1016/j.cbi.2014.12.015 |
| [52] | Verma, K., Gupta, N., Zang, T., Wangtrakluldee, P., Srivastava, S.K., Penning, T.M., et al. (2018) AKR1C3 Inhibitor KV-37 Exhibits Antineoplastic Effects and Potentiates Enzalutamide in Combination Therapy in Prostate Adenocarcinoma Cells. Molecular Cancer Therapeutics, 17, 1833-1845. https://doi.org/10.1158/1535-7163.mct-17-1023 |
| [53] | Endo, S., Hu, D., Matsunaga, T., Otsuji, Y., El-Kabbani, O., Kandeel, M., et al. (2014) Synthesis of Non-Prenyl Analogues of Baccharin as Selective and Potent Inhibitors for Aldo-Keto Reductase 1C3. Bioorganic & Medicinal Chemistry, 22, 5220-5233. https://doi.org/10.1016/j.bmc.2014.08.007 |
| [54] | Verma, K., Zang, T., Penning, T.M. and Trippier, P.C. (2019) Potent and Highly Selective Aldo-Keto Reductase 1C3 (AKR1C3) Inhibitors Act as Chemotherapeutic Potentiators in Acute Myeloid Leukemia and T-Cell Acute Lymphoblastic Leukemia. Journal of Medicinal Chemistry, 62, 3590-3616. https://doi.org/10.1021/acs.jmedchem.9b00090 |
| [55] | Hulcová, D., Breiterová, K., Zemanová, L., Siatka, T., Šafratová, M., Vaněčková, N., et al. (2017) AKR1C3 Inhibitory Potency of Naturally-Occurring Amaryllidaceae Alkaloids of Different Structural Types. Natural Product Communications, 12, 245-246. https://doi.org/10.1177/1934578x1701200226 |
| [56] | Li, J., Tian, Y., Zhao, L., Wang, Y., Zhang, H., Xu, D., et al. (2016) Berberine Inhibits Androgen Synthesis by Interaction with Aldo-Keto Reductase 1C3 in 22Rv1 Prostate Cancer Cells. Asian Journal of Andrology, 18, 607-612. https://doi.org/10.4103/1008-682x.169997 |
| [57] | Santos, A.R.N., Sheldrake, H.M., Ibrahim, A.I.M., Danta, C.C., Bonanni, D., Daga, M., et al. (2019) Exploration of [2 + 2 + 2] Cyclotrimerisation Methodology to Prepare Tetrahydroisoquinoline-Based Compounds with Potential Aldo-Keto Reductase 1C3 Target Affinity. MedChemComm, 10, 1476-1480. https://doi.org/10.1039/c9md00201d |
| [58] | Novotná, E., Büküm, N., Hofman, J., Flaxová, M., Kouklíková, E., Louvarová, D., et al. (2018) Roscovitine and Purvalanol a Effectively Reverse Anthracycline Resistance Mediated by the Activity of Aldo-Keto Reductase 1C3 (AKR1C3): A Promising Therapeutic Target for Cancer Treatment. Biochemical Pharmacology, 156, 22-31. https://doi.org/10.1016/j.bcp.2018.08.001 |
| [59] | Novotná, E., Büküm, N., Hofman, J., Flaxová, M., Kouklíková, E., Louvarová, D., et al. (2018) Aldo-Keto Reductase 1C3 (AKR1C3): A Missing Piece of the Puzzle in the Dinaciclib Interaction Profile. Archives of Toxicology, 92, 2845-2857. https://doi.org/10.1007/s00204-018-2258-0 |
| [60] | Bukum, N., Novotna, E., Morell, A., Hofman, J. and Wsol, V. (2019) Buparlisib Is a Novel Inhibitor of Daunorubicin Reduction Mediated by Aldo-Keto Reductase 1C3. Chemico-Biological Interactions, 302, 101-107. https://doi.org/10.1016/j.cbi.2019.01.026 |
| [61] | Zhao, Y., Zheng, X., Zhang, H., Zhai, J., Zhang, L., Li, C., et al. (2015) In Vitro Inhibition of AKR1CS by Sulphonylureas and the Structural Basis. Chemico-Biological Interactions, 240, 310-315. https://doi.org/10.1016/j.cbi.2015.09.006 |
| [62] | Byrns, M.C., Steckelbroeck, S. and Penning, T.M. (2008) An Indomethacin Analogue, N-(4-Chlorobenzoyl)-Melatonin, Is a Selective Inhibitor of Aldo-Keto Reductase 1C3 (Type 2 3α-HSD, Type 5 17β-HSD, and Prostaglandin F Synthase), a Potential Target for the Treatment of Hormone Dependent and Hormone Independent Malignancies. Biochemical Pharmacology, 75, 484-493. https://doi.org/10.1016/j.bcp.2007.09.008 |
| [63] | Flanagan, J.U., Yosaatmadja, Y., Teague, R.M., Chai, M.Z.L., Turnbull, A.P. and Squire, C.J. (2012) Crystal Structures of Three Classes of Non-Steroidal Anti-Inflammatory Drugs in Complex with Aldo-Keto Reductase 1C3. PLOS ONE, 7, e43965. https://doi.org/10.1371/journal.pone.0043965 |
| [64] | Liedtke, A.J., Adeniji, A.O., Chen, M., Byrns, M.C., Jin, Y., Christianson, D.W., et al. (2013) Development of Potent and Selective Indomethacin Analogues for the Inhibition of AKR1C3 (Type 5 17β-Hydroxysteroid Dehydrogenase/Prostaglandin F Synthase) in Castrate-Resistant Prostate Cancer. Journal of Medicinal Chemistry, 56, 2429-2446. https://doi.org/10.1021/jm3017656 |
| [65] | Adeniji, A.O., Twenter, B.M., Byrns, M.C., Jin, Y., Chen, M., Winkler, J.D., et al. (2012) Development of Potent and Selective Inhibitors of Aldo-Keto Reductase 1C3 (Type 5 17-Hydroxysteroid Dehydrogenase) Based on n-Phenyl-Aminobenzoates and Their Structure-Activity Relationships. Journal of Medicinal Chemistry, 55, 2311-2323. https://doi.org/10.1021/jm201547v |
| [66] | Pippione, A.C., Carnovale, I.M., Bonanni, D., Sini, M., Goyal, P., Marini, E., et al. (2018) Potent and Selective Aldo-Keto Reductase 1C3 (AKR1C3) Inhibitors Based on the Benzoisoxazole Moiety: Application of a Bioisosteric Scaffold Hopping Approach to Flufenamic Acid. European Journal of Medicinal Chemistry, 150, 930-945. https://doi.org/10.1016/j.ejmech.2018.03.040 |
| [67] | Pippione, A.C., Giraudo, A., Bonanni, D., Carnovale, I.M., Marini, E., Cena, C., et al. (2017) Hydroxytriazole Derivatives as Potent and Selective Aldo-Keto Reductase 1C3 (AKR1C3) Inhibitors Discovered by Bioisosteric Scaffold Hopping Approach. European Journal of Medicinal Chemistry, 139, 936-946. https://doi.org/10.1016/j.ejmech.2017.08.046 |
| [68] | Hendriks, C.M.M., Penning, T.M., Zang, T., Wiemuth, D., Gründer, S., Sanhueza, I.A., et al. (2015) Pentafluorosulfanyl-containing Flufenamic Acid Analogs: Syntheses, Properties and Biological Activities. Bioorganic & Medicinal Chemistry Letters, 25, 4437-4440. https://doi.org/10.1016/j.bmcl.2015.09.012 |
| [69] | Féau, C., Arnold, L.A., Kosinski, A., Zhu, F., Connelly, M. and Guy, R.K. (2009) Novel Flufenamic Acid Analogues as Inhibitors of Androgen Receptor Mediated Transcription. ACS Chemical Biology, 4, 834-843. https://doi.org/10.1021/cb900143a |
| [70] | Chen, M., Adeniji, A.O., Twenter, B.M., Winkler, J.D., Christianson, D.W. and Penning, T.M. (2012) Crystal Structures of AKR1C3 Containing an N-(Aryl)amino-Benzoate Inhibitor and a Bifunctional AKR1C3 Inhibitor and Androgen Receptor Antagonist. Therapeutic Leads for Castrate Resistant Prostate Cancer. Bioorganic & Medicinal Chemistry Letters, 22, 3492-3497. https://doi.org/10.1016/j.bmcl.2012.03.085 |
| [71] | Wangtrakuldee, P., Adeniji, A.O., Zang, T., Duan, L., Khatri, B., Twenter, B.M., et al. (2019) A 3-(4-Nitronaphthen-1-Yl) Amino-Benzoate Analog as a Bifunctional AKR1C3 Inhibitor and AR Antagonist: Head to Head Comparison with Other Advanced AKR1C3 Targeted Therapeutics. The Journal of Steroid Biochemistry and Molecular Biology, 192, Article ID: 105283. https://doi.org/10.1016/j.jsbmb.2019.01.001 |
