A patent review on aldehyde dehydrogenase inhibitors: an overview of small molecule inhibitors from the last decade

References

• Black W, Vasiliou V. The aldehyde dehydrogenase gene superfamily resource center. Hum Genomics. 2009 Dec;4(2):136–142. doi: 10.1186/1479-7364-4-2-136
   PubMedGoogle Scholar
• Yoshida A, Rzhetsky A, Hsu LC, et al. Human aldehyde dehydrogenase gene family. Eur J Biochem. 1998 Feb 1;251(3):549–557. doi: 10.1046/j.1432-1327.1998.2510549.x
   PubMedGoogle Scholar
• Crabb DW, Matsumoto M, Chang D, et al. Overview of the role of alcohol dehydrogenase and aldehyde dehydrogenase and their variants in the genesis of alcohol-related pathology. Proc Nutr Soc. 2004 Feb;63(1):49–63. doi: 10.1079/PNS2003327
   PubMed Web of Science ®Google Scholar
• Rice KL, Izon DJ, Ford J, et al. Overexpression of stem cell associated ALDH1A1, a target of the leukemogenic transcription factor TLX1/HOX11, inhibits lymphopoiesis and promotes myelopoiesis in murine hematopoietic progenitors. Leuk Res. 2008 Jun;32(6):873–883. doi: 10.1016/j.leukres.2007.11.001
   PubMed Web of Science ®Google Scholar
• Alnouti Y, Klaassen CD. Tissue distribution, ontogeny, and regulation of aldehyde dehydrogenase (Aldh) enzymes mRNA by prototypical microsomal enzyme inducers in mice. Toxicol Sci. 2008 Jan;101(1):51–64. doi: 10.1093/toxsci/kfm280
   PubMed Web of Science ®Google Scholar
• Koppaka V, Thompson DC, Chen Y, et al. Aldehyde dehydrogenase inhibitors: a comprehensive review of the pharmacology, mechanism of action, substrate specificity, and clinical application. Pharmacol Rev. 2012 Jul;64(3):520–539. doi: 10.1124/pr.111.005538
   PubMed Web of Science ®Google Scholar
• Xu X, Chai S, Wang P, et al. Aldehyde dehydrogenases and cancer stem cells. Cancer Lett. 2015 Dec 1;369(1):50–57. doi: 10.1016/j.canlet.2015.08.018
   PubMed Web of Science ®Google Scholar
• Pors K, Moreb JS. Aldehyde dehydrogenases in cancer: an opportunity for biomarker and drug development? Drug Discov Today. 2014 Dec;19(12):1953–1963. doi: 10.1016/j.drudis.2014.09.009
   PubMedGoogle Scholar
• Chen Y, Koppaka V, Thompson DC, et al. Focus on molecules: ALDH1A1: from lens and corneal crystallin to stem cell marker. Exp Eye Res. 2012 Sep;102:105–106.
   PubMed Web of Science ®Google Scholar
• Tomita H, Tanaka K, Tanaka T, et al. Aldehyde dehydrogenase 1A1 in stem cells and cancer. Oncotarget. 2016 Mar 8;7(10):11018–11032. doi: 10.18632/oncotarget.6920
   PubMedGoogle Scholar
• King G, Holmes R. Human corneal and lens aldehyde dehydrogenases. Purification and properties of human lens ALDH1 and differential expression as major soluble proteins in human lens (ALDH1) and cornea (ALDH3). Adv Exp Med Biol. 1997;414:19–27.
   PubMedGoogle Scholar
• Chen Y, Orlicky DJ, Matsumoto A, et al. Aldehyde dehydrogenase 1B1 (ALDH1B1) is a potential biomarker for human colon cancer. Biochem Biophys Res Commun. 2011 Feb 11;405(2):173–179. doi: 10.1016/j.bbrc.2011.01.002
   PubMed Web of Science ®Google Scholar
• Ahadome SD, Abraham DJ, Rayapureddi S, et al. Aldehyde dehydrogenase inhibition blocks mucosal fibrosis in human and mouse ocular scarring. JCI Insight. 2016 Aug 4;1(12):e87001. doi: 10.1172/jci.insight.87001
   PubMed Web of Science ®Google Scholar
• Ma Z, Jiang L, Li B, et al. Discovery of benzimidazole derivatives as potent and selective aldehyde dehydrogenase 1A1 (ALDH1A1) inhibitors with glucose consumption improving activity. Bioorg Med Chem. 2021 Sep 15;46:116352.
   PubMed Web of Science ®Google Scholar
• Sanders TJ, McCarthy NE, Giles EM, et al. Increased production of retinoic acid by intestinal macrophages contributes to their inflammatory phenotype in patients with Crohn’s disease. Gastroenterology. 2014 May;146(5):1278–88.e1. doi: 10.1053/j.gastro.2014.01.057
   PubMed Web of Science ®Google Scholar
• Kiefer FW, Orasanu G, Nallamshetty S, et al. Retinaldehyde dehydrogenase 1 coordinates hepatic gluconeogenesis and lipid metabolism. Endocrinology. 2012 Jul;153(7):3089–3099. doi: 10.1210/en.2011-2104
   PubMed Web of Science ®Google Scholar
• Kiefer FW, Vernochet C, O’Brien P, et al. Retinaldehyde dehydrogenase 1 regulates a thermogenic program in white adipose tissue. Nat Med. 2012 Jun;18(6):918–925. doi: 10.1038/nm.2757
   PubMed Web of Science ®Google Scholar
• Ziouzenkova O, Orasanu G, Sharlach M, et al. Retinaldehyde represses adipogenesis and diet-induced obesity. Nat Med. 2007 Jun;13(6):695–702. doi: 10.1038/nm1587
   PubMed Web of Science ®Google Scholar
• Gentry T, Foster S, Winstead L, et al. Simultaneous isolation of human BM hematopoietic, endothelial and mesenchymal progenitor cells by flow sorting based on aldehyde dehydrogenase activity: implications for cell therapy. Cytotherapy. 2007;9(3):259–274. doi: 10.1080/14653240701218516
   PubMed Web of Science ®Google Scholar
• Zhang M, Shoeb M, Goswamy J, et al. Overexpression of aldehyde dehydrogenase 1A1 reduces oxidation-induced toxicity in SH-SY5Y neuroblastoma cells. J Neurosci Res. 2010 Feb 15;88(3):686–694. doi: 10.1002/jnr.22230
   PubMed Web of Science ®Google Scholar
• Black W, Chen Y, Matsumoto A, et al. Molecular mechanisms of ALDH3A1-mediated cellular protection against 4-hydroxy-2-nonenal. Free Radic Biol Med. 2012 May 1;52(9):1937–1944. doi: 10.1016/j.freeradbiomed.2012.02.050
   PubMed Web of Science ®Google Scholar
• Moretti A, Li J, Donini S, et al. Crystal structure of human aldehyde dehydrogenase 1A3 complexed with NAD+ and retinoic acid. Sci Rep. 2016 Oct 19;6(1):35710. doi: 10.1038/srep35710
   PubMed Web of Science ®Google Scholar
• Li J, Garavaglia S, Ye Z, et al. A specific inhibitor of ALDH1A3 regulates retinoic acid biosynthesis in glioma stem cells. Commun Biol. 2021 Dec 21;4(1):1420. doi: 10.1038/s42003-021-02949-7
   PubMed Web of Science ®Google Scholar
• Yamashita D, Minata M, Ibrahim AN, et al. Identification of ALDH1A3 as a Viable therapeutic target in breast cancer metastasis-Initiating cells. Mol Cancer Ther. 2020 May;19(5):1134–1147. doi: 10.1158/1535-7163.MCT-19-0461
   PubMed Web of Science ®Google Scholar
• Parajuli B, Georgiadis TM, Fishel ML, et al. Development of selective inhibitors for human aldehyde dehydrogenase 3A1 (ALDH3A1) for the enhancement of cyclophosphamide cytotoxicity. Chembiochem. 2014 Mar 21;15(5):701–712.
   PubMed Web of Science ®Google Scholar
• Matsunaga N, Ogino T, Hara Y, et al. Optimized dosing schedule based on circadian dynamics of mouse breast cancer stem cells improves the antitumor effects of aldehyde dehydrogenase inhibitor. Cancer Res. 2018 Jul 1;78(13):3698–3708. doi: 10.1158/0008-5472.CAN-17-4034
   PubMed Web of Science ®Google Scholar
• Thomas ML, de Antueno R, Coyle KM, et al. Citral reduces breast tumor growth by inhibiting the cancer stem cell marker ALDH1A3. Mol Oncol. 2016 Nov;10(9):1485–1496. doi: 10.1016/j.molonc.2016.08.004
   PubMed Web of Science ®Google Scholar
• Chen C-H, Ferreira JCB, Gross ER, et al. Targeting aldehyde dehydrogenase 2: new therapeutic opportunities. Physiol Rev. 2014 Jan;94(1):1–34. doi: 10.1152/physrev.00017.2013
   PubMed Web of Science ®Google Scholar
• Marchitti SA, Brocker C, Stagos D, et al. Non-P450 aldehyde oxidizing enzymes: the aldehyde dehydrogenase superfamily. Expert Opin Drug Metab Toxicol. 2008 Jun;4(6):697–720. doi: 10.1517/17425255.4.6.697
   PubMed Web of Science ®Google Scholar
• Yang S-J, Wang H-Y, Li X-Q, et al. Genetic polymorphisms of ADH2 and ALDH2 association with esophageal cancer risk in southwest China. World J Gastroenterol. 2007 Nov 21;13(43):5760–5764. doi: 10.3748/wjg.v13.i43.5760
   PubMed Web of Science ®Google Scholar
• Wang L-S, Wu Z-X. ALDH2 and cancer therapy. Adv Exp Med Biol. 2019;1193:221–228.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Ren J. ALDH2 in alcoholic heart diseases: molecular mechanism and clinical implications. Pharmacol Ther. 2011 Oct;132(1):86–95. doi: 10.1016/j.pharmthera.2011.05.008
   PubMed Web of Science ®Google Scholar
• Li C, Li X, Chang Y, et al. Aldehyde dehydrogenase-2 Attenuates myocardial Remodeling and contractile dysfunction induced by a high-fat diet. Cell Physiol Biochem. 2018 Aug 9;48(5):1843–1853. doi: 10.1159/000492506
   PubMedGoogle Scholar
• Doser TA, Turdi S, Thomas DP, et al. Transgenic overexpression of aldehyde dehydrogenase-2 rescues chronic alcohol intake-induced myocardial hypertrophy and contractile dysfunction. Circulation. 2009 Apr 14;119(14):1941–1949.
   PubMed Web of Science ®Google Scholar
• Sun A, Cheng Y, Zhang Y, et al. Aldehyde dehydrogenase 2 ameliorates doxorubicin-induced myocardial dysfunction through detoxification of 4-HNE and suppression of autophagy. J Mol Cell Cardiol. 2014 Jun;71:92–104.
   PubMed Web of Science ®Google Scholar
• Kang P, Wang J, Fang D, et al. Activation of ALDH2 attenuates high glucose induced rat cardiomyocyte fibrosis and necroptosis. Free Radic Biol Med. 2020 Jan;146:198–210.
   PubMed Web of Science ®Google Scholar
• Ma X, Luo Q, Zhu H, et al. Aldehyde dehydrogenase 2 activation ameliorates CCl4 -induced chronic liver fibrosis in mice by up-regulating Nrf2/HO-1 antioxidant pathway. J Cell Mol Med. 2018 Aug;22(8):3965–3978. doi: 10.1111/jcmm.13677
   PubMed Web of Science ®Google Scholar
• Zhao Y, Wang B, Zhang J, et al. ALDH2 (aldehyde dehydrogenase 2) protects against hypoxia-induced pulmonary hypertension. Arterioscler Thromb Vasc Biol. 2019 Nov;39(11):2303–2319. doi: 10.1161/ATVBAHA.119.312946
   PubMed Web of Science ®Google Scholar
• Mizuno Y, Harada E, Morita S, et al. East asian variant of aldehyde dehydrogenase 2 is associated with coronary spastic angina: possible roles of reactive aldehydes and implications of alcohol flushing syndrome. Circulation. 2015 May 12;131(19):1665–1673. doi: 10.1161/CIRCULATIONAHA.114.013120
   PubMed Web of Science ®Google Scholar
• Ebert AD, Kodo K, Liang P, et al. Characterization of the molecular mechanisms underlying increased ischemic damage in the aldehyde dehydrogenase 2 genetic polymorphism using a human induced pluripotent stem cell model system. Sci Transl Med. 2014 Sep 24;6(255):255ra130. doi: 10.1126/scitranslmed.3009027
   PubMed Web of Science ®Google Scholar
• Ma S, Cao F. Targeting ALDH2 in atherosclerosis: molecular mechanisms and therapeutic opportunities. Adv Exp Med Biol. 2019;1193:211–220.
   PubMed Web of Science ®Google Scholar
• Kobayashi H, Nakamura S, Sato Y, et al. ALDH2 mutation promotes skeletal muscle atrophy in mice via accumulation of oxidative stress. Bone. 2021 Jan;142:115739.
   PubMed Web of Science ®Google Scholar
• Kikuchi N, Tajima T, Tamura Y, et al. The ALDH2 rs671 polymorphism is associated with athletic status and muscle strength in a Japanese population. Biol Sport. 2022 Mar;39(2):429–434. doi: 10.5114/biolsport.2022.106151
   PubMed Web of Science ®Google Scholar
• Xu T, Guo J, Wei M, et al. Aldehyde dehydrogenase 2 protects against acute kidney injury by regulating autophagy via the beclin-1 pathway. JCI Insight. 2021 Aug 9;6(15): doi: 10.1172/jci.insight.138183
   Web of Science ®Google Scholar
• Li Y, Liu S-L, Qi S-H. ALDH2 protects against ischemic stroke in rats by facilitating 4-HNE clearance and AQP4 Down-regulation. Neurochem Res. 2018 Jul;43(7):1339–1347. doi: 10.1007/s11064-018-2549-0
   PubMed Web of Science ®Google Scholar
• Li X, Weng X, Shi H, et al. Acetaldehyde dehydrogenase 2 deficiency exacerbates cardiac fibrosis by promoting mobilization and homing of bone marrow fibroblast progenitor cells. J Mol Cell Cardiol. 2019 Dec;137:107–118.
   PubMed Web of Science ®Google Scholar
• Arolfo MP, Overstreet DH, Yao L, et al. Suppression of heavy drinking and alcohol seeking by a selective ALDH-2 inhibitor. Alcohol Clin Exp Res. 2009 Nov;33(11):1935–1944. doi: 10.1111/j.1530-0277.2009.01031.x
   PubMed Web of Science ®Google Scholar
• Benedetti A, Comporti M, Esterbauer H. Identification of 4-hydroxynonenal as a cytotoxic product originating from the peroxidation of liver microsomal lipids. Biochim Biophys Acta. 1980 Nov 7;620(2):281–296.
   PubMed Web of Science ®Google Scholar
• Lassen N, Bateman JB, Estey T, et al. Multiple and additive functions of ALDH3A1 and ALDH1A1: cataract phenotype and ocular oxidative damage in Aldh3a1(-/-)/Aldh1a1(-/-) knock-out mice. J Biol Chem. 2007 Aug 31;282(35):25668–25676. doi: 10.1074/jbc.M702076200
   PubMed Web of Science ®Google Scholar
• Kim K-J, Pearl PL, Jensen K, et al. Succinic semialdehyde dehydrogenase: biochemical-molecular-clinical disease mechanisms, redox regulation, and functional significance. Antioxid Redox Signal. 2011 Aug 1;15(3):691–718. doi: 10.1089/ars.2010.3470
   PubMed Web of Science ®Google Scholar
• Chan C-L, Wong JWY, Wong C-P, et al. Human antiquitin: structural and functional studies. Chem Biol Interact. 2011 May 30;191(1–3):165–170. doi: 10.1016/j.cbi.2010.12.019
   PubMed Web of Science ®Google Scholar
• Chen Z, Foster MW, Zhang J, et al. An essential role for mitochondrial aldehyde dehydrogenase in nitroglycerin bioactivation. Proc Natl Acad Sci, USA. 2005 Aug 23;102(34):12159–12164. doi: 10.1073/pnas.0503723102
   PubMed Web of Science ®Google Scholar
• Sládek NE. Human aldehyde dehydrogenases: potential pathological, pharmacological, and toxicological impact. J Biochem Mol Toxicol. 2003;17(1):7–23. doi: 10.1002/jbt.10057
   PubMed Web of Science ®Google Scholar
• Shortall K, Djeghader A, Magner E, et al. Insights into aldehyde dehydrogenase enzymes: a structural perspective. Front Mol Biosci. 2021 May 14;8:659550. doi: 10.3389/fmolb.2021.659550
   PubMed Web of Science ®Google Scholar
• Morgan CA, Hurley TD. Development of a high-throughput in vitro assay to identify selective inhibitors for human ALDH1A1. Chem Biol Interact. 2015 Jun 5;234: 29–37. doi: 10.1016/j.cbi.2014.10.028
   PubMed Web of Science ®Google Scholar
• Liu L-K, Tanner JJ. Crystal structure of aldehyde dehydrogenase 16 reveals trans-Hierarchical structural similarity and a new dimer. J Mol Biol. 2019 Feb 1;431(3):524–541.
   PubMed Web of Science ®Google Scholar
• Končitíková R, Vigouroux A, Kopečná M, et al. Kinetic and structural analysis of human ALDH9A1. Biosci Rep. 2019 Apr 30;39(4): doi: 10.1042/BSR20190558
   PubMedGoogle Scholar
• Zhang X, Ouyang Z. Crystal structure of aldehyde dehydrogenase 1A1 from mouse. Biochem Biophys Res Commun. 2022 Nov 5;628:141–146. doi: 10.1016/j.bbrc.2022.08.054
   PubMed Web of Science ®Google Scholar
• Chen Y, Zhu J-Y, Hong KH, et al. Structural basis of ALDH1A2 inhibition by irreversible and reversible small molecule inhibitors. ACS Chem Biol. 2018 Mar 16;13(3):582–590. doi: 10.1021/acschembio.7b00685
   PubMed Web of Science ®Google Scholar
• Castellví A, Pequerul R, Barracco V, et al. Structural and biochemical evidence that ATP inhibits the cancer biomarker human aldehyde dehydrogenase 1A3. Commun Biol. 2022 Apr 13;5(1):354. doi: 10.1038/s42003-022-03311-1
   PubMed Web of Science ®Google Scholar
• Quattrini L, Gelardi ELM, Coviello V, et al. Imidazo[1,2-a]pyridine Derivatives as Aldehyde Dehydrogenase Inhibitors: Novel Chemotypes to Target Glioblastoma Stem Cells. J Med Chem. 2020 May 14;63(9):4603–4616. doi: 10.1021/acs.jmedchem.9b01910
   PubMed Web of Science ®Google Scholar
• Gelardi ELM, Colombo G, Picarazzi F, et al. A selective competitive inhibitor of aldehyde dehydrogenase 1A3 hinders cancer cell growth, invasiveness and stemness in vitro. Cancers (Basel). 2021 Jan 19;13(2):356. doi: 10.3390/cancers13020356
   PubMed Web of Science ®Google Scholar
• Sobreira TJP, Marlétaz F, Simões-Costa M, et al. Structural shifts of aldehyde dehydrogenase enzymes were instrumental for the early evolution of retinoid-dependent axial patterning in metazoans. Proc Natl Acad Sci, USA. 2011 Jan 4;108(1):226–231. doi: 10.1073/pnas.1011223108
   PubMed Web of Science ®Google Scholar
• Pequerul R, Vera J, Giménez-Dejoz J, et al. Structural and kinetic features of aldehyde dehydrogenase 1A (ALDH1A) subfamily members, cancer stem cell markers active in retinoic acid biosynthesis. Arch Biochem Biophys. 2020 Mar 15;681:108256.
   PubMed Web of Science ®Google Scholar
• Kimble-Hill AC, Parajuli B, Chen C-H, et al. Development of selective inhibitors for aldehyde dehydrogenases based on substituted indole-2,3-diones. J Med Chem. 2014 Feb 13;57(3):714–722. doi: 10.1021/jm401377v
   PubMed Web of Science ®Google Scholar
• Morgan CA, Hurley TD. Characterization of two distinct structural classes of selective aldehyde dehydrogenase 1A1 inhibitors. J Med Chem. 2015 Feb 26;58(4):1964–1975.
   PubMed Web of Science ®Google Scholar
• Keung WM, Vallee BL. Daidzin: a potent, selective inhibitor of human mitochondrial aldehyde dehydrogenase. Proc Natl Acad Sci, USA. 1993 Feb 15;90(4):1247–1251. doi: 10.1073/pnas.90.4.1247
   PubMed Web of Science ®Google Scholar
• Yang S-M, Yasgar A, Miller B, et al. Discovery of NCT-501, a potent and selective theophylline-based inhibitor of aldehyde dehydrogenase 1A1 (ALDH1A1). J Med Chem. 2015 Aug 13;58(15):5967–5978. doi:10.1021/acs.jmedchem.5b00577
   PubMed Web of Science ®Google Scholar
• Kulsum S, Sudheendra HV, Pandian R, et al. Cancer stem cell mediated acquired chemoresistance in head and neck cancer can be abrogated by aldehyde dehydrogenase 1 A1 inhibition. Mol Carcinog. 2017 Feb;56(2):694–711. doi: 10.1002/mc.22526
   PubMed Web of Science ®Google Scholar
• Yang S-M, Martinez NJ, Yasgar A, et al. Discovery of orally bioavailable, quinoline-based aldehyde dehydrogenase 1A1 (ALDH1A1) inhibitors with potent cellular activity. J Med Chem. 2018 Jun 14;61(11):4883–4903. doi: 10.1021/acs.jmedchem.8b00270
   PubMed Web of Science ®Google Scholar
• Cheng P, Wang J, Waghmare I, et al. FOXD1-ALDH1A3 signaling is a determinant for the self-Renewal and tumorigenicity of mesenchymal glioma stem cells. Cancer Res. 2016 Dec 15;76(24):7219–7230. doi: 10.1158/0008-5472.CAN-15-2860
   PubMed Web of Science ®Google Scholar
• Overstreet DH, Knapp DJ, Breese GR, et al. A selective ALDH-2 inhibitor reduces anxiety in rats. Pharmacol Biochem Behav. 2009 Dec;94(2):255–261. doi: 10.1016/j.pbb.2009.09.004
   PubMed Web of Science ®Google Scholar
• Wang B, Buchman CD, Li L, et al. Enrichment of chemical libraries docked to protein conformational ensembles and application to aldehyde dehydrogenase 2. J Chem Inf Model. 2014 Jul 28;54(7):2105–2116. doi: 10.1021/ci5002026
   PubMed Web of Science ®Google Scholar
• Parajuli B, Fishel ML, Hurley TD. Selective ALDH3A1 inhibition by benzimidazole analogues increase mafosfamide sensitivity in cancer cells. J Med Chem. 2014 Jan 23;57(2):449–461.
   PubMed Web of Science ®Google Scholar
• Khanna M, Chen C-H, Kimble-Hill A, et al. Discovery of a novel class of covalent inhibitor for aldehyde dehydrogenases. J Biol Chem. 2011 Dec 16;286(50):43486–43494. doi: 10.1074/jbc.M111.293597
   PubMed Web of Science ®Google Scholar
• Okazaki S, Shintani S, Hirata Y, et al. Synthetic lethality of the ALDH3A1 inhibitor dyclonine and xCT inhibitors in glutathione deficiency-resistant cancer cells. Oncotarget. 2018 Sep 18;9(73):33832–33843. doi: 10.18632/oncotarget.26112
   PubMedGoogle Scholar
• Zhou L, Sheng D, Wang D, et al. Identification of cancer-type specific expression patterns for active aldehyde dehydrogenase (ALDH) isoforms in ALDEFLUOR assay. Cell Biol Toxicol. 2019 Apr;35(2):161–177. doi: 10.1007/s10565-018-9444-y
   PubMed Web of Science ®Google Scholar
• Rodríguez-Zavala JS, Calleja LF, Moreno-Sánchez R, et al. Role of aldehyde dehydrogenases in physiopathological processes. Chem Res Toxicol. 2019 Mar 18;32(3):405–420. doi: 10.1021/acs.chemrestox.8b00256
   PubMed Web of Science ®Google Scholar
• Morgan CA, Parajuli B, Buchman CD, et al. N,N-diethylaminobenzaldehyde (DEAB) as a substrate and mechanism-based inhibitor for human ALDH isoenzymes. Chem Biol Interact. 2015 Jun 5;234:18–28. doi: 10.1016/j.cbi.2014.12.008
   PubMed Web of Science ®Google Scholar
• Müller CA, Banas R. Disulfiram: an anticraving substance? AJP. 2011 Jan;168(1):98–98. doi: 10.1176/appi.ajp.2010.10070943
   Google Scholar
• Nie D, Chen C, Li Y, et al. Disulfiram, an aldehyde dehydrogenase inhibitor, works as a potent drug against sepsis and cancer via NETosis, pyroptosis, apoptosis, ferroptosis, and cuproptosis. Blood Sci. 2022 Jul 1;4(3):152–154.
   PubMedGoogle Scholar
• Fournet G, Martin G, Quash G. α,β-acetylenic amino thiolester inhibitors of aldehyde dehydrogenases 1&3: suppressors of apoptogenic aldehyde oxidation and activators of apoptosis. Curr Med Chem. 2013 Feb 1;20(4):527–533.
   PubMed Web of Science ®Google Scholar
• Pérez-Alea M, McGrail K, Sánchez-Redondo S, et al. ALDH1A3 is epigenetically regulated during melanocyte transformation and is a target for melanoma treatment. Oncogene. 2017 Oct 12;36(41):5695–5708. doi: 10.1038/onc.2017.160
   PubMed Web of Science ®Google Scholar
• Nordin N, Yeap SK, Rahman HS, et al. In vitro cytotoxicity and anticancer effects of citral nanostructured lipid carrier on MDA MBA-231 human breast cancer cells. Sci Rep. 2019 Feb 7;9(1):1614. doi: 10.1038/s41598-018-38214-x
   PubMedGoogle Scholar
• Dinavahi SS, Gowda R, Gowda K, et al. Development of a novel multi-isoform ALDH inhibitor effective as an antimelanoma agent. Mol Cancer Ther. 2020 Feb;19(2):447–459. doi: 10.1158/1535-7163.MCT-19-0360
   PubMed Web of Science ®Google Scholar
• Jofre-Bonet M, Sindelar JL, Petrakis IL, et al. Cost effectiveness of disulfiram: treating cocaine use in methadone-maintained patients. J Subst Abuse Treat. 2004 Apr;26(3):225–232. doi: 10.1016/S0740-5472(04)00004-2
   PubMed Web of Science ®Google Scholar
• Cannizaro CE, Graupe M, Guerrero JA, et al. Amygdala Neurosciences, Inc. Compounds for the treatment of addiction. US 10,507,215 B2. 2018.
   Google Scholar
• Bilokin Y, Zablocki J, Abelman M, et al. CV Therapeutics Inc. ALDH-2 inhibitors in the treatment of addiction. WO 2008/014497 A2.
   Google Scholar
• Bilokin Y, Elzein E, Zablocki J, et al. CV Therapeutics, Inc. ALDH-2 inhibitors in the treatment of addiction. WO 2009/094028 A1. 2009.
   Google Scholar
• Zablocki J, Abelman M, Organ M, et al. CV Therapeutics, Inc. Quinazolinone derivatives as ALDH-2inhibitors. US 2008/0249116 A1. 2008.
   Google Scholar
• Chen C-H, Yang W, Mochly-Rosen D, et al. The board of trustees of the le- land Stanford Junior University. Aldehydedehydrogenase-1 modulators and methods of use thereof. WO 2014/160034 A1. 2014.
   Google Scholar
• Yang W, Chen C-H, Mochly-Rosen D, et al. The board of trustees of the le- land Stanford Junior University. Mitochondrial aldehyde dehydrogenase-2 modulators and methods of use thereof. WO 2014/160185 A2. 2014.
   Google Scholar
• Hurley TD, Chen C-H, Mochly-Rosen D, et al. The board of trustees of the le- land Stanford Junior University. Aldehyde dehydrogenase inhibitors and methods of use thereof. WO 2015/084731 A1. 2015.
   Google Scholar
• Chen JK, Feng Z, Hom ME, et al. The board of trustees of the le- land Stanford Junior University. Isoform-specific aldehyde dehydrogenase inhibitors. WO 2021/257696 A1. 2021.
   Google Scholar
• Blackburn B, Diamond I, Lange LG, et al. Amygdala Biosciences, Inc. Combination therapy for preventing addiction. WO 2019/079209 A1. 2019.
   Google Scholar
• Blackburn B Amygdala Neurosciences, Inc. Combination therapy for nicotine addiction. WO 2020/023792 Al. 2020.
   Google Scholar
• Maloney DJ, Yang S-M, Jadhav AP, et al. The United States of America, as represented by the Secretary, department of Health and human Services. Small molecule aldehyde dehydrogenase inhibitors and methods of use thereof. WO 2016/086008 A1. 2016.
   Google Scholar
• Yang SM, Maloney DJ, Martinez N, et al. The United States of America, as represented by the Secretary, department of Health and human Services and Yale University. Substituted quinoline analogs as aldehyde dehydrogenase 1A1 (ALDH1A1) inhibitors. WO 2019/089626 A1. 2019.
   Google Scholar
• Raha D, Settleman J, Wilson TR, et al. Genetech, Inc. And F-Hoffman-La Roche AG. Methods of treating cancer and preventing drug resistance. WO 2014/128235 A1. 2014.
   Google Scholar
• Robertson G, Dinavahi VSS, Doreswamy RGC, et al. The Penn state research Foundation. Methods and compositions relating to inhibition of aldehyde dehydrogenases for treatment of cancer. WO 2021/252749 A1. 2021.
   Google Scholar
• Esposito M, Proudfoot J, Kang Y, et al. KayoThera, Inc. And the trustees of Princeton University. Heterocyclic compounds and uses therof. WO 2022/226383 A1. 2022.
   Google Scholar
• Larsen SD, Huddle BC, Yang K, et al. The regents of the University of Michigan and Indiana University research and Technology Corporation. Small molecule inhibitors of ALDH and uses thereof. WO 2017/223086 A1. 2017.
   Google Scholar
• Graupe M, Venkatramani C, Zablocki J, et al. Gliead Sciences, Inc. ALDH-2 inhibitors in the treatment of addiction. WO 2013/033377 A1. 2013.
   Google Scholar
• Goldstein AS, Amory J, Paik J, et al. University of Washington. Inhibitor compounds for male contraception. WO 2020/123855 A1. 2020.
   Google Scholar
• Amory JK, Muller CH, Shimshoni JA, et al. Suppression of spermatogenesis by bisdichloroacetyldiamines is mediated by inhibition of testicular retinoic acid biosynthesis. J Androl. 2011;32(1):111–119. doi: 10.2164/jandrol.110.010751
   PubMedGoogle Scholar
• Shicang Y, Jiangjie D, Jun W, et al. First Affiliated Hospital Third Military Medical University Chinese People’s Liberation Army P.R. Applications of YD1701 in preparation of drugs for treating ALDH1A3 high - expression tumors. US 2021/0186925 A1. 2021.
   Google Scholar
• Feldberg L, Sabouni A, Bailey T, et al. Sophrosyne Pharmaceuticals Limited. Compounds and methods for treating alcohol use disorder. WO 2022/115742 A1. 2022.
   Google Scholar