The Comparative Metabolism of a Novel Hepatocellular Carcinoma Therapeutic Agent, 2,3-Diamino-N-(4-(benzo[d]thiazol-2-yl)phenyl)propanamide, in Human and Animal Hepatocytes
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals and Reagents
2.2. Metabolic Stability
2.3. Metabolite Characterization in Human and Animal Hepatocytes
2.4. Screening of CYP Enzymes and CES Isozymes Responsible for the Metabolism of ETN101
2.5. Characterization of Responsible NAT Isozymes for the Metabolism of ETN101
2.6. LC-MS Analysis
3. Results
3.1. Metabolic Stability of ETN101 in Hepatocytes
3.2. Metabolite Characterization of ETN101 in Hepatocytes
3.3. Characterization of Drug-Metabolizing Enzymes Responsible for ETN101 Metabolism
3.3.1. Human cDNA-Expressed CYP Enzymes
3.3.2. Human Recombinant CES Isozymes
3.3.3. Human Liver Cytosolic NAT1 and NAT2
3.3.4. Human Recombinant NAT1
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- El-Serag, H.B.; Rudolph, K.L. Hepatocellular carcinoma: Epidemiology and molecular carcinogenesis. Gastroenterology 2007, 132, 2557–2576. [Google Scholar] [CrossRef] [PubMed]
- El-Serag, H.B. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology 2012, 142, 1264–1273.e61. [Google Scholar] [CrossRef] [PubMed]
- Tang, A.; Hallouch, O.; Chernyak, V.; Kamaya, A.; Sirlin, C.B. Epidemiology of hepatocellular carcinoma: Target population for surveillance and diagnosis. Abdom. Radiol. 2018, 43, 13–25. [Google Scholar] [CrossRef] [PubMed]
- Garrido, A.; Djouder, N. Cirrhosis: A Questioned Risk Factor for Hepatocellular Carcinoma. Trends Cancer 2021, 7, 29–36. [Google Scholar] [CrossRef] [PubMed]
- Yang, J.D.; Heimbach, J.K. New advances in the diagnosis and management of hepatocellular carcinoma. BMJ 2020, 371, m3544. [Google Scholar] [CrossRef] [PubMed]
- Uchino, K.; Tateishi, R.; Shiina, S.; Kanda, M.; Masuzaki, R.; Kondo, Y.; Goto, T.; Omata, M.; Yoshida, H.; Koike, K. Hepatocellular carcinoma with extrahepatic metastasis: Clinical features and prognostic factors. Cancer 2011, 117, 4475–4483. [Google Scholar] [CrossRef] [PubMed]
- Yang, J.D.; Roberts, L.R. Hepatocellular carcinoma: A global view. Nat. Rev. Gastroenterol. Hepatol. 2010, 7, 448–458. [Google Scholar] [CrossRef] [PubMed]
- Younossi, Z.M.; Otgonsuren, M.; Henry, L.; Venkatesan, C.; Mishra, A.; Erario, M.; Hunt, S. Association of nonalcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma (HCC) in the United States from 2004 to 2009. Hepatology 2015, 62, 1723–1730. [Google Scholar] [CrossRef] [PubMed]
- Wang, C.; Wang, X.; Gong, G.; Ben, Q.; Qiu, W.; Chen, Y.; Li, G.; Wang, L. Increased risk of hepatocellular carcinoma in patients with diabetes mellitus: A systematic review and meta-analysis of cohort studies. Int. J. Cancer 2012, 130, 1639–1648. [Google Scholar] [CrossRef]
- Ganne-Carrie, N.; Chaffaut, C.; Bourcier, V.; Archambeaud, I.; Perarnau, J.M.; Oberti, F.; Roulot, D.; Moreno, C.; Louvet, A.; Dao, T.; et al. Estimate of hepatocellular carcinoma incidence in patients with alcoholic cirrhosis. J. Hepatol. 2018, 69, 1274–1283. [Google Scholar] [CrossRef]
- Balogh, J.; Victor, D., 3rd; Asham, E.H.; Burroughs, S.G.; Boktour, M.; Saharia, A.; Li, X.; Ghobrial, R.M.; Monsour, H.P., Jr. Hepatocellular carcinoma: A review. J. Hepatocell. Carcinoma 2016, 3, 41–53. [Google Scholar] [CrossRef] [PubMed]
- Akamatsu, N.; Cillo, U.; Cucchetti, A.; Donadon, M.; Pinna, A.D.; Torzilli, G.; Kokudo, N. Surgery and Hepatocellular Carcinoma. Liver Cancer 2016, 6, 44–50. [Google Scholar] [CrossRef]
- Llovet, J.M.; Ricci, S.; Mazzaferro, V.; Hilgard, P.; Gane, E.; Blanc, J.F.; de Oliveira, A.C.; Santoro, A.; Raoul, J.L.; Forner, A.; et al. Sorafenib in advanced hepatocellular carcinoma. N. Engl. J. Med. 2008, 359, 378–390. [Google Scholar] [CrossRef] [PubMed]
- Cheng, A.L.; Kang, Y.K.; Chen, Z.; Tsao, C.J.; Qin, S.; Kim, J.S.; Luo, R.; Feng, J.; Ye, S.; Yang, T.S.; et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: A phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009, 10, 25–34. [Google Scholar] [CrossRef] [PubMed]
- Kudo, M.; Finn, R.S.; Qin, S.; Han, K.H.; Ikeda, K.; Piscaglia, F.; Baron, A.; Park, J.W.; Han, G.; Jassem, J.; et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: A randomised phase 3 non-inferiority trial. Lancet 2018, 391, 1163–1173. [Google Scholar] [CrossRef] [PubMed]
- Tang, W.; Chen, Z.; Zhang, W.; Cheng, Y.; Zhang, B.; Wu, F.; Wang, Q.; Wang, S.; Rong, D.; Reiter, F.P.; et al. The mechanisms of sorafenib resistance in hepatocellular carcinoma: Theoretical basis and therapeutic aspects. Signal Transduct. Target. Ther. 2020, 5, 87. [Google Scholar] [CrossRef] [PubMed]
- Bruix, J.; Qin, S.; Merle, P.; Granito, A.; Huang, Y.H.; Bodoky, G.; Pracht, M.; Yokosuka, O.; Rosmorduc, O.; Breder, V.; et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2017, 389, 56–66. [Google Scholar] [CrossRef]
- Abou-Alfa, G.K.; Meyer, T.; Cheng, A.L.; El-Khoueiry, A.B.; Rimassa, L.; Ryoo, B.Y.; Cicin, I.; Merle, P.; Chen, Y.; Park, J.W.; et al. Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma. N. Engl. J. Med. 2018, 379, 54–63. [Google Scholar] [CrossRef] [PubMed]
- Zhu, A.X.; Kang, Y.K.; Yen, C.J.; Finn, R.S.; Galle, P.R.; Llovet, J.M.; Assenat, E.; Brandi, G.; Pracht, M.; Lim, H.Y.; et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased alpha-fetoprotein concentrations (REACH-2): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019, 20, 282–296. [Google Scholar] [CrossRef]
- van Doorn, D.J.; Takkenberg, R.B.; Klumpen, H.J. Immune Checkpoint Inhibitors in Hepatocellular Carcinoma: An Overview. Pharmaceuticals 2020, 14, 3. [Google Scholar] [CrossRef]
- El-Khoueiry, A.B.; Sangro, B.; Yau, T.; Crocenzi, T.S.; Kudo, M.; Hsu, C.; Kim, T.Y.; Choo, S.P.; Trojan, J.; Welling, T.H.R.; et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): An open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet 2017, 389, 2492–2502. [Google Scholar] [CrossRef] [PubMed]
- Zhu, A.X.; Finn, R.S.; Edeline, J.; Cattan, S.; Ogasawara, S.; Palmer, D.; Verslype, C.; Zagonel, V.; Fartoux, L.; Vogel, A.; et al. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): A non-randomised, open-label phase 2 trial. Lancet Oncol. 2018, 19, 940–952. [Google Scholar] [CrossRef] [PubMed]
- Cui, T.M.; Liu, Y.; Wang, J.B.; Liu, L.X. Adverse Effects of Immune-Checkpoint Inhibitors in Hepatocellular Carcinoma. Onco Targets Ther. 2020, 13, 11725–11740. [Google Scholar] [CrossRef]
- Yang, J.D.; Hainaut, P.; Gores, G.J.; Amadou, A.; Plymoth, A.; Roberts, L.R. A global view of hepatocellular carcinoma: Trends, risk, prevention and management. Nat. Rev. Gastroenterol. Hepatol. 2019, 16, 589–604. [Google Scholar] [CrossRef] [PubMed]
- Park, H.J.; Choi, G.; Ha, S.; Kim, Y.; Choi, M.J.; Kim, M.; Islam, M.K.; Chang, Y.; Kwon, T.J.; Kim, D.; et al. MBP-11901 Inhibits Tumor Growth of Hepatocellular Carcinoma through Multitargeted Inhibition of Receptor Tyrosine Kinases. Cancers 2022, 14, 1994. [Google Scholar] [CrossRef]
- Islam, M.K.; Baek, A.R.; Sung, B.; Yang, B.W.; Choi, G.; Park, H.J.; Kim, Y.H.; Kim, M.; Ha, S.; Lee, G.H.; et al. Synthesis, Characterization, and Anticancer Activity of Benzothiazole Aniline Derivatives and Their Platinum (II) Complexes as New Chemotherapy Agents. Pharmaceuticals 2021, 14, 832. [Google Scholar] [CrossRef] [PubMed]
- Muhamad, N.; Na-Bangchang, K. Metabolite Profiling in Anticancer Drug Development: A Systematic Review. Drug Des. Dev. Ther. 2020, 14, 1401–1444. [Google Scholar] [CrossRef] [PubMed]
- He, C.; Wan, H. Drug metabolism and metabolite safety assessment in drug discovery and development. Expert Opin. Drug Metab. Toxicol. 2018, 14, 1071–1085. [Google Scholar] [CrossRef]
- Wu, Y.; Pan, L.; Chen, Z.; Zheng, Y.; Diao, X.; Zhong, D. Metabolite Identification in the Preclinical and Clinical Phase of Drug Development. Curr. Drug Metab. 2021, 22, 838–857. [Google Scholar] [CrossRef]
- FDA. Safety Testing of Drug Metabolites Guidance for Industry. 2020. Available online: https://www.fda.gov/media/72279/download (accessed on 1 July 2024).
- Cuyckens, F. Mass spectrometry in drug metabolism and pharmacokinetics: Current trends and future perspectives. Rapid Commun. Mass Spectrom. 2019, 33 (Suppl. S3), 90–95. [Google Scholar] [CrossRef]
- Lee, M.S.; Shim, H.J.; Cho, Y.Y.; Lee, J.Y.; Kang, H.C.; Song, I.S.; Lee, H.S. Comparative metabolism of aschantin in human and animal hepatocytes. Arch. Pharm. Res. 2024, 47, 111–126. [Google Scholar] [CrossRef] [PubMed]
- Saurina, J.; Sentellas, S. Liquid chromatography coupled to mass spectrometry for metabolite profiling in the field of drug discovery. Expert. Opin. Drug Discov. 2019, 14, 469–483. [Google Scholar] [CrossRef] [PubMed]
- Kim, J.H.; Kim, D.K.; Choi, W.G.; Ji, H.Y.; Choi, J.S.; Song, I.S.; Lee, S.; Lee, H.S. In Vitro Metabolism of DWP16001, a Novel Sodium-Glucose Cotransporter 2 Inhibitor, in Human and Animal Hepatocytes. Pharmaceutics 2020, 12, 865. [Google Scholar] [CrossRef]
- Kukongviriyapan, V.; Phromsopha, N.; Tassaneeyakul, W.; Kukongviriyapan, U.; Sripa, B.; Hahnvajanawong, V.; Bhudhisawasdi, V. Inhibitory effects of polyphenolic compounds on human arylamine N-acetyltransferase 1 and 2. Xenobiotica 2006, 36, 15–28. [Google Scholar] [CrossRef]
- Sun, Q.; Harper, T.W.; Dierks, E.A.; Zhang, L.; Chang, S.; Rodrigues, A.D.; Marathe, P. 1-Aminobenzotriazole, a known cytochrome P450 inhibitor, is a substrate and inhibitor of N-acetyltransferase. Drug Metab. Dispos. 2011, 39, 1674–1679. [Google Scholar] [CrossRef] [PubMed]
- Kong, T.Y.; Kim, J.H.; Kwon, S.S.; Cheong, J.C.; Kim, H.S.; In, M.K.; Lee, H.S. Inhibition of cytochrome P450 and uridine 5′-diphospho-glucuronosyltransferases by MAM-2201 in human liver microsomes. Arch. Pharm. Res. 2017, 40, 727–735. [Google Scholar] [CrossRef] [PubMed]
- Patki, K.C.; Von Moltke, L.L.; Greenblatt, D.J. In vitro metabolism of midazolam, triazolam, nifedipine, and testosterone by human liver microsomes and recombinant cytochromes p450: Role of cyp3a4 and cyp3a5. Drug Metab. Dispos. 2003, 31, 938–944. [Google Scholar] [CrossRef]
- Lucas, D.; Ferrara, R.; Gonzalez, E.; Bodenez, P.; Albores, A.; Manno, M.; Berthou, F. Chlorzoxazone, a selective probe for phenotyping CYP2E1 in humans. Pharmacogenetics 1999, 9, 377–388. [Google Scholar] [CrossRef]
- Shi, J.; Wang, X.; Eyler, R.F.; Liang, Y.; Liu, L.; Mueller, B.A.; Zhu, H.J. Association of Oseltamivir Activation with Gender and Carboxylesterase 1 Genetic Polymorphisms. Basic Clin. Pharmacol. Toxicol. 2016, 119, 555–561. [Google Scholar] [CrossRef]
- Xu, G.; Zhang, W.; Ma, M.K.; McLeod, H.L. Human carboxylesterase 2 is commonly expressed in tumor tissue and is correlated with activation of irinotecan. Clin. Cancer Res. 2002, 8, 2605–2611. [Google Scholar]
- Goodfellow, G.H.; Dupret, J.M.; Grant, D.M. Identification of amino acids imparting acceptor substrate selectivity to human arylamine acetyltransferases NAT1 and NAT2. Biochem. J. 2000, 348 Pt 1, 159–166. [Google Scholar] [CrossRef] [PubMed]
- Sloczynska, K.; Gunia-Krzyzak, A.; Koczurkiewicz, P.; Wojcik-Pszczola, K.; Zelaszczyk, D.; Popiol, J.; Pekala, E. Metabolic stability and its role in the discovery of new chemical entities. Acta Pharm. 2019, 69, 345–361. [Google Scholar] [CrossRef] [PubMed]
- Di, L. The Impact of Carboxylesterases in Drug Metabolism and Pharmacokinetics. Curr. Drug Metab. 2019, 20, 91–102. [Google Scholar] [CrossRef] [PubMed]
- Bradshaw, T.D.; Wrigley, S.; Shi, D.F.; Schultz, R.J.; Paull, K.D.; Stevens, M.F. 2-(4-Aminophenyl)benzothiazoles: Novel agents with selective profiles of in vitro anti-tumour activity. Br. J. Cancer 1998, 77, 745–752. [Google Scholar] [CrossRef] [PubMed]
- Dubey, R.; Shrivastava, P.K.; Basniwal, P.K.; Bhattacharya, S.; Moorthy, N.S. 2-(4-aminophenyl) benzothiazole: A potent and selective pharmacophore with novel mechanistic action towards various tumour cell lines. Mini Rev. Med. Chem. 2006, 6, 633–637. [Google Scholar] [CrossRef] [PubMed]
- Loaiza-Perez, A.I.; Trapani, V.; Hose, C.; Singh, S.S.; Trepel, J.B.; Stevens, M.F.; Bradshaw, T.D.; Sausville, E.A. Aryl hydrocarbon receptor mediates sensitivity of MCF-7 breast cancer cells to antitumor agent 2-(4-amino-3-methylphenyl) benzothiazole. Mol. Pharmacol. 2002, 61, 13–19. [Google Scholar] [CrossRef] [PubMed]
- Bradshaw, T.D.; Trapani, V.; Vasselin, D.A.; Westwell, A.D. The aryl hydrocarbon receptor in anticancer drug discovery: Friend or foe? Curr. Pharm. Des. 2002, 8, 2475–2490. [Google Scholar] [CrossRef] [PubMed]
- Bradshaw, T.D.; Westwell, A.D. The development of the antitumour benzothiazole prodrug, Phortress, as a clinical candidate. Curr. Med. Chem. 2004, 11, 1009–1021. [Google Scholar] [CrossRef] [PubMed]
- Martignoni, M.; Groothuis, G.M.; de Kanter, R. Species differences between mouse, rat, dog, monkey and human CYP-mediated drug metabolism, inhibition and induction. Expert Opin. Drug Metab. Toxicol. 2006, 2, 875–894. [Google Scholar] [CrossRef]
- Chua, M.S.; Shi, D.F.; Wrigley, S.; Bradshaw, T.D.; Hutchinson, I.; Shaw, P.N.; Barrett, D.A.; Stanley, L.A.; Stevens, M.F. Antitumor benzothiazoles. 7. Synthesis of 2-(4-acylaminophenyl)benzothiazoles and investigations into the role of acetylation in the antitumor activities of the parent amines. J. Med. Chem. 1999, 42, 381–392. [Google Scholar] [CrossRef]
Parameters | Human | Mouse | Rat | Dog | Monkey |
---|---|---|---|---|---|
t1/2 (min) | 75.0 | 120.4 | 68.9 | 112.7 | 73.1 |
Clint (μL/min/106 cells) | 18.5 | 11.5 | 20.1 | 12.3 | 19.0 |
Clint,hep (mL/min/kg) | 66.1 | 135.8 | 94.1 | 84.6 | 45.7 |
ID | ETN101 and Metabolites | Elemental Composition | Exact Mass ([M + H]+) | tR (min) | Product Ions (m/z) | Species |
---|---|---|---|---|---|---|
ETN101 | C16H16N4OS | 313.1123 | 5.9 | 65.0393, 109.0110, 118.0528, 227.0638 | ||
Hydrolysis | ||||||
M1 | CJM-126 | C13H10N2S | 227.0643 | 10.1 | 65.0393, 109.0111, 118.0529 | H, M, R, D, Mk |
N-acetylation of M1 | ||||||
M2 | N-Acetyl-CJM-126 | C15H12N2OS | 269.0749 | 9.9 | 65.0391, 109.0109, 118.0528, 227.0639 | H, M, R, Mk |
Hydroxylation of M1 | ||||||
M3 | 6-OH-CJM-126 | C13H10N2OS | 243.0592 | 7.6 | 81.0341, 118.0528, 125.0057 | H, M, R, D, Mk |
M4 | OH-CJM-126 | C13H10N2OS | 243.0592 | 8.2 | 81.0340, 125.0058 | H, M, R, D |
M5 | 3′-OH-CJM-126 | C13H10N2OS | 243.0592 | 9.0 | 65.0393, 109.0110, 134.0476 | H, M, R, D, Mk |
M6 | OH-CJM-126 | C13H10N2OS | 243.0592 | 9.5 | Not acquired | R, Mk |
M7 | OH-CJM-126 | C13H10N2OS | 243.0592 | 9.7 | 109.0110, 134.0475 | H, M, R, D, Mk |
M8 | OH-CJM-126 | C13H10N2OS | 243.0592 | 10.1 | 109.0110, 134.0475 | M, R, D, Mk |
Glucuronidation of M1 | ||||||
M9 | CJM-126 glucuronide | C19H18N2O6S | 403.0964 | 8.1 | 109.0109, 118.0527, 227.0639 | H, M, R, D, Mk |
Sulfation of M1 | ||||||
M10 | CJM-126 sulfate | C13H10N2O3S2 | 307.0211 | 9.1 | Not acquired | R |
Hydroxylation + glucuronidation of M1 | ||||||
M11 | OH-CJM-126 glucuronide | C19H18N2O7S | 419.0908 | 7.4 | 118.0529, 125.0058, 243.0586 | H, M, R |
M12 | OH-CJM-126 glucuronide | C19H18N2O7S | 419.0908 | 7.9 | 65.0392, 109.0109, 134.0475, 243.0585 | H, M, R, D, Mk |
M13 | OH-CJM-126 glucuronide | C19H18N2O7S | 419.0908 | 8.3 | 65.0392, 109.0109, 134.0475, 243.0585 | H, D, Mk |
Hydroxylation + sulfation on M1 | ||||||
M14 | OH-CJM-126 sulfate | C13H10N2O4S2 | 323.0155 | 7.0 | Not acquired | M, R, D |
M15 | OH-CJM-126 sulfate | C13H10N2O4S2 | 323.0155 | 7.3 | 118.0528, 125.0058, 243.0588 | H, M, R, D |
M16 | OH-CJM-126 sulfate | C13H10N2O4S2 | 323.0155 | 7.8 | Not acquired | H, R, Mk |
M17 | OH-CJM-126 sulfate | C13H10N2O4S2 | 323.0155 | 9.7 | 109.0109, 134.0476, 243.0587 | H, M, R, D, Mk |
Hydroxylation + N-acetylation of M1 | ||||||
M18 | N-Acetyl-OH-CJM-126 | C15H12N2O2S | 285.0692 | 8.0 | 81.0341, 118.0527, 125.0056, 243.0587 | M, Mk |
M19 | N-Acetyl-OH-CJM-126 | C15H12N2O2S | 285.0692 | 8.3 | 81.0341, 118.0527, 125.0056, 243.0587 | H, D, Mk |
M20 | N-Acetyl-OH-CJM-126 | C15H12N2O2S | 285.0692 | 9.3 | 109.0110, 227.0637 | H, R, D, Mk |
M21 | N-Acetyl-OH-CJM-126 | C15H12N2O2S | 285.0692 | 9.8 | 109.0109, 243.0589 | H, Mk |
Hydroxylation + N-acetylation + glucuronidation of M1 | ||||||
M22 | N-Acetyl-OH-CJM-126 glucuronide | C21H20N2O8S | 461.1013 | 6.4 | Not acquired | Mk |
Dihydroxylation of M1 | ||||||
M23 | di-OH-CJM-126 | C13H10N2O2S | 259.0541 | 7.2 | Not acquired | H, R |
M24 | di-OH-CJM-126 | C13H10N2O2S | 259.0541 | 8.4 | Not acquired | H, D |
M25 | di-OH-CJM-126 | C13H10N2O2S | 259.0541 | 9.5 | Not acquired | Mk |
M26 | di-OH-CJM-126 | C13H10N2O2S | 259.0541 | 10.4 | Not acquired | D |
Dihydroxylation + sulfation on M1 | ||||||
M27 | di-OH-CJM-126 sulfate | C13H10N2O5S2 | 339.0104 | 7.0 | Not acquired | D |
M28 | di-OH-CJM-126 sulfate | C13H10N2O5S2 | 339.0104 | 7.2 | Not acquired | H, R |
M29 | di-OH-CJM-126 sulfate | C13H10N2O5S2 | 339.0104 | 8.4 | Not acquired | D |
Hydroxylation | ||||||
M30 | OH-ETN101 | C16H16N4O2S | 329.1072 | 1.1 | 118.0529, 125.0057, 243.0586 | H, D, Mk |
M31 | OH-ETN101 | C16H16N4O2S | 329.1072 | 1.8 | 118.0529, 125.0057, 243.0586 | H, Mk |
M32 | OH-ETN101 | C16H16N4O2S | 329.1072 | 5.5 | Not acquired | H, Mk |
M33 | OH-ETN101 | C16H16N4O2S | 329.1072 | 7.1 | Not acquired | D, Mk |
M34 | OH-ETN101 | C16H16N4O2S | 329.1072 | 7.9 | Not acquired | Mk |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Jung, Y.-H.; Lee, D.-C.; Kwon, Y.-M.; Jang, E.; Choi, G.; Kim, Y.-H.; Kim, T.H.; Kim, J.-H. The Comparative Metabolism of a Novel Hepatocellular Carcinoma Therapeutic Agent, 2,3-Diamino-N-(4-(benzo[d]thiazol-2-yl)phenyl)propanamide, in Human and Animal Hepatocytes. Metabolites 2024, 14, 425. https://doi.org/10.3390/metabo14080425
Jung Y-H, Lee D-C, Kwon Y-M, Jang E, Choi G, Kim Y-H, Kim TH, Kim J-H. The Comparative Metabolism of a Novel Hepatocellular Carcinoma Therapeutic Agent, 2,3-Diamino-N-(4-(benzo[d]thiazol-2-yl)phenyl)propanamide, in Human and Animal Hepatocytes. Metabolites. 2024; 14(8):425. https://doi.org/10.3390/metabo14080425
Chicago/Turabian StyleJung, Young-Heun, Dong-Cheol Lee, Ye-Min Kwon, Eunbee Jang, Garam Choi, Yeoun-Hee Kim, Tae Hwan Kim, and Ju-Hyun Kim. 2024. "The Comparative Metabolism of a Novel Hepatocellular Carcinoma Therapeutic Agent, 2,3-Diamino-N-(4-(benzo[d]thiazol-2-yl)phenyl)propanamide, in Human and Animal Hepatocytes" Metabolites 14, no. 8: 425. https://doi.org/10.3390/metabo14080425