Preclinical Pharmacokinetics of Triptolide: A Potential Antitumor Drug

Author(s): Wei Song, Meilin Liu, Junjun Wu, Hong Zhai, Yong Chen*, Zhihong Peng*.

Journal Name: Current Drug Metabolism

Volume 20 , Issue 2 , 2019

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Graphical Abstract:


Background: Triptolide, a bioactive component in Tripterygium wilfordii extracts, possess strong antiproliferative activity on all 60-National Cancer Institute (NCI) cancer cell lines. However, the widespread use of triptolide in the clinical practice is greatly limited for its multi-organ toxicity and narrow therapeutic window. All the toxic characteristics of triptolide are associated with the pharmacokinetics especially its distribution and accumulation in the target organ.

Methods: The literature review was done using PubMed search, SciFinder and Google Scholar databases with specific keywords such as triptolide, pharmacokinetics, drug-drug interaction, transporters, metabolism, modification to collect the related full-length articles and abstracts from 2000 to 2018.

Results: Oral triptolide is rapidly and highly absorbed. Grapefruit juice affects oral absorption, increasing the area under the concentration-time curve (AUC) by 153 % and the maximum concentration (Cmax) by 141 %. The AUC and the Cmax are not dose proportional. Triptolide distributes into the liver, heart, spleen, lung and kidney. Biotransformation of triptolide in rats includes hydroxylation, sulfate, glucuronide, N-acetylcysteine (NAC) and Glutathione (GSH) conjugation and combinations of these pathways. Less than 4 % of triptolide was recovered from the feces, bile and urine within 24 h. After repeating dosage, triptolide was eliminated quickly without accumulation in vivo. As a substrate of P-glycoprotein (P-gp) and CYP3A4, triptolide could have clinically significant pharmacokinetic interactions with those proteins substrates/inhibitors.

Conclusion: The findings of this review confirm the importance of pharmacokinetic character for understanding the pharmacology and toxicology of triptolide.

Keywords: Triptolide, pharmacokinetics, toxicity, metabolism, drug-drug interaction, antitumor.

Semenza, G.L.; Ruvolo, P.P. Introduction to tumor microenvironment regulation of cancer cell survival, metastasis, inflammation, and immune surveillance. Biochim. Biophys. Acta, 2016, 1863(3), 379-381.
Heger, M.; Van Golen, R.F.; Broekgaarden, M.; Michel, M.C. The molecular basis for the pharmacokinetics and pharmacodynamics of curcumin and its metabolites in relation to cancer. Pharmacol. Rev., 2014, 66(1), 222-307.
No authors listed. Cancer multidrug resistance. Nat. Biotechnol., 2000, 18, IT18-IT20.
Sakalar, C.; Izgi, K.; Iskender, B.; Sezen, S.; Aksu, H.; Cakir, M.; Kurt, B.; Turan, A.; Canatan, H. The combination of thymoquinone and paclitaxel shows anti-tumor activity through the interplay with apoptosis network in triple-negative breast cancer. Tumour Biol., 2016, 37(4), 4467-4477.
Hu, L.; Pang, S.; Hu, Q.; Gu, D.; Kong, D.; Xiong, X.; Su, J. Enhanced antitumor efficacy of folate targeted nanoparticles co-loaded with docetaxel and curcumin. Biomed. Pharmacother., 2015, 75, 26-32.
Li, X.T.; He, M.L.; Zhou, Z.Y.; Jiang, Y.; Cheng, L. The antitumor activity of PNA modified vinblastine cationic liposomes on Lewis lung tumor cells: In vitro and in vivo evaluation. Int. J. Pharm., 2015, 487(1-2), 223-233.
Xu, Y.; Qiu, L. Nonspecifically enhanced therapeutic effects of vincristine on multidrug-resistant cancers when coencapsulated with quinine in liposomes. Int. J. Nanomedicine, 2015, 10, 4225-4237.
Florea, A.M.; Busselberg, D. Cisplatin as an anti-tumor drug: Cellular mechanisms of activity, drug resistance and induced side effects. Cancers (Basel), 2011, 3(1), 1351-1371.
Liu, C.; Ge, X.G.; Hao, Q.X.; Guo, L.P.; Yuan, Q.J.; Huang, L.Q. Investigation Report of Tripterygium wilfordii and Tripterygium hypoglaucum. Zhong Yao Cai, 2015, 38(2), 249-253.
Guo, L.; Duan, L.; Liu, K.; Liu, E.H.; Li, P. Chemical comparison of Tripterygium wilfordii and Tripterygium hypoglaucum based on quantitative analysis and chemometrics methods. J. Pharm. Biomed. Anal., 2014, 95, 220-228.
Brincks, E.L.; Kucaba, T.A.; James, B.R.; Murphy, K.A.; Schwertfeger, K.L.; Sangwan, V.; Banerjee, S.; Saluja, A.K.; Griffith, T.S. Triptolide enhances the tumoricidal activity of TRAIL against renal cell carcinoma. FEBS J., 2015, (24), 4747-4765.
Grzegorzewska, A.E.; Frankiewicz, D.; Breborowicz, D.; Matlawska, I.; Bylka, W. Disseminated cutaneous Kaposi sarcoma in a patient receiving triptolide/tripdiolide for rheumatoid arthritis. Med. Sci. Monit., 2012, 18(8), CS67-CS71.
Zheng, Y.; Zhang, W.J.; Wang, X.M. Triptolide with potential medicinal value for diseases of the central nervous system. CNS Neurosci. Ther., 2013, 19(2), 76-82.
Zhang, Z.; Qu, X.; Ni, Y.; Zhang, K.; Dong, Z.; Yan, X.; Qin, J.; Sun, H.; Ding, Y.; Zhao, P.; Gong, K. Triptolide protects rat heart against pressure overload-induced cardiac fibrosis. Int. J. Cardiol., 2013, 168(3), 2498-2505.
Li, J.; Liu, R.; Yang, Y.; Huang, Y.; Li, X.; Liu, R.; Shen, X. Triptolide-induced in vitro and in vivo cytotoxicity in human breast cancer stem cells and primary breast cancer cells. Oncol. Rep., 2014, 31(5), 2181-2186.
Liu, L.; Salnikov, A.V.; Bauer, N.; Aleksandrowicz, E.; Labsch, S.; Nwaeburu, C.; Mattern, J.; Gladkich, J.; Schemmer, P.; Werner, J.; Herr, I. Triptolide reverses hypoxia-induced epithelial-mesenchymal transition and stem-like features in pancreatic cancer by NF-kappaB downregulation. Int. J. Cancer, 2014, 134(10), 2489-2503.
Banerjee, S.; Saluja, A. Minnelide, a novel drug for pancreatic and liver cancer. Pancreatology, 2015, 15(4)(Suppl.), S39-S43.
Wu, J.; Li, Q.Q.; Zhou, H.; Lu, Y.; Li, J.M.; Ma, Y.; Wang, L.; Fu, T.; Gong, X.; Weintraub, M.; Wu, S.; Ding, H. Selective tumor cell killing by triptolide in p53 wild-type and p53 mutant ovarian carcinomas. Med. Oncol., 2014, 31(7), 14.
Reno, T.A.; Kim, J.Y.; Raz, D.J. Triptolide inhibits lung cancer cell migration, invasion, and metastasis. Ann. Thorac. Surg., 2015, 100(5), 1817-1824.
Huang, M.; Zhang, H.; Liu, T.; Tian, D.; Gu, L.; Zhou, M. Triptolide inhibits MDM2 and induces apoptosis in acute lymphoblastic leukemia cells through a p53-independent pathway. Mol. Cancer Ther., 2013, 12(2), 184-194.
Li, J.; Zhu, W.; Leng, T.; Shu, M.; Huang, Y.; Xu, D.; Qiu, P.; Su, X.; Yan, G. Triptolide-induced cell cycle arrest and apoptosis in human renal cell carcinoma cells. Oncol. Rep., 2011, 25(4), 979-987.
Zhu, W.; Li, J.; Wu, S.; Li, S.; Le, L.; Su, X.; Qiu, P.; Hu, H.; Yan, G. Triptolide cooperates with Cisplatin to induce apoptosis in gemcitabine-resistant pancreatic cancer. Pancreas, 2012, 41(7), 1029-1038.
Chen, Z.; Sangwan, V.; Banerjee, S.; Chugh, R.; Dudeja, V.; Vickers, S.M.; Saluja, A.K. Triptolide sensitizes pancreatic cancer cells to TRAIL-induced activation of the death receptor pathway. Cancer Lett., 2014, 348(1-2), 156-166.
Li, Y.; Hu, S. Triptolide sensitizes liver cancer cell lines to chemotherapy in vitro and in vivo. Panminerva Med., 2014, 56(3), 211-220.
Gali-Muhtasib, H.; Hmadi, R.; Kareh, M.; Tohme, R.; Darwiche, N. Cell death mechanisms of plant-derived anticancer drugs: beyond apoptosis. Apoptosis, 2015, 20(12), 1531-1562.
Oliveira, A.; Beyer, G.; Chugh, R.; Skube, S.J.; Majumder, K.; Banerjee, S.; Sangwan, V.; Li, L.; Dawra, R.; Subramanian, S.; Saluja, A.; Dudeja, V. Triptolide abrogates growth of colon cancer and induces cell cycle arrest by inhibiting transcriptional activation of E2F. Lab. Invest., 2015, 95(6), 648-659.
Nakazato, T.; Sagawa, M.; Kizaki, M. Triptolide induces apoptotic cell death of multiple myeloma cells via transcriptional repression of Mcl-1. Int. J. Oncol., 2014, 44(4), 1131-1138.
Titov, D.V.; Gilman, B.; He, Q.L.; Bhat, S.; Low, W.K.; Dang, Y.; Smeaton, M.; Demain, A.L.; Miller, P.S.; Kugel, J.F.; Goodrich, J.A.; Liu, J.O. XPB, a subunit of TFIIH, is a target of the natural product triptolide. Nat. Chem. Biol., 2011, 7(3), 182-188.
He, Q.L.; Titov, D.V.; Li, J.; Tan, M.; Ye, Z.; Zhao, Y.; Romo, D.; Liu, J.O. Covalent modification of a cysteine residue in the XPB subunit of the general transcription factor TFIIH through single epoxide cleavage of the transcription inhibitor triptolide. Angew. Chem. Int. Ed. Engl., 2015, 54(6), 1859-1863.
Jin, J.; Sun, X.; Zhao, Z.; Wang, W.; Qiu, Y.; Fu, X.; Huang, M.; Huang, Z. Activation of the farnesoid X receptor attenuates triptolide-induced liver toxicity. Phytomedicine, 2015, 22(10), 894-901.
Li, X.X.; Du, F.Y.; Liu, H.X.; Ji, J.B.; Xing, J. Investigation of the active components in Tripterygium wilfordii leading to its acute hepatotoxicity and nephrotoxicity. J. Ethnopharmacol., 2015, 162, 238-243.
Singla, N.; Challana, S. Reproductive toxicity of triptolide in male house rat, Rattus rattus. Sci. World J., 2014, 2014, 879405.
Lu, Y.; Xie, T.; Zhang, Y.; Zhou, F.; Ruan, J.; Zhu, W.; Zhu, H.; Feng, Z.; Zhou, X. Triptolide Induces hepatotoxicity via inhibition of CYP450s in Rat liver microsomes. BMC Complement. Altern. Med., 2017, 17(1), 15.
Singla, N.; Challana, S. Reproductive toxicity of triptolide in male house rat, Rattus rattus. Sci. World J., 2014, 2014, 879405.
Shao, F.; Wang, G.; Xie, H.; Zhu, X.; Sun, J.A.J. Pharmacokinetic study of triptolide, a constituent of immunosuppressive chinese herb medicine, in rats. Biol. Pharm. Bull., 2007, 30(4), 702-707.
Shao, F.; Wang, G.; Sun, J.; Xie, H.; Li, H.; Liang, Y.; Zhang, R.; Zhu, X. Liquid chromatographic/mass spectrometry assay of triptolide in dog plasma and its application to pharmacokinetic study. J. Pharm. Biomed. Anal., 2006, 41(2), 341-346.
Shao, F.; Wang, G.J.; Sun, J.G.; Xie, H.T.; Zhang, R.; Zhu, X.Y. Pharmacokinetics of triptolide in Beagle dogs. Yao Xue Xue Bao, 2007, 42(1), 61-65.
Gong, X.; Chen, Y.; Wu, Y. Absorption and metabolism characteristics of triptolide as determined by a sensitive and reliable LC-MS/MS method. Molecules, 2015, 20(5), 8928-8940.
Toutain, P.L.; Ferran, A.; Bousquet-Melou, A. Species differences in pharmacokinetics and pharmacodynamics. In: Comparative and Veterinary Pharmacology., Handbook of Experimental Pharmacology, Ed: Springer, Berlin, Heidelberg. 2010. Vol. 199: pp. 19-48.
Kratochwil, N.A.; Huber, W.; Muller, F.; Kansy, M.; Gerber, P.R. Predicting plasma protein binding of drugs: A new approach. Biochem. Pharmacol., 2002, 64(9), 1355-1374.
Olson, R.E.; Christ, D.D. Plasma protein binding of drugs. Annu. Rep. Med. Chem., 1996, 31, 327-336.
Liu, P-X.; Wang, J.; Zhuang, X-M.; Zhang, Y-J.; Zhang, Z-Q.; Ruan, J-X. Plasma protein binding characteristics of triptolide in several species. Military Med. Sci., 2012, 36(7), 528-530.
Li, M.; Hu, T.; Tie, C.; Qu, L.; Zheng, H.; Zhang, J. Quantitative proteomics and targeted fatty acids analysis reveal the damage of triptolide in liver and kidney. Proteomics, 2017, 17(22), 1700001.
Peng, Z.H.; Wang, J.J.; Du, P.; Chen, Y. Identification of in vivo and in vitro metabolites of triptolide by liquid chromatography-tandem mass spectrometry. J. Pharm. Biomed. Anal., 2012, 70, 624-630.
Shen, G.; Zhuang, X.; Xiao, W.; Kong, L.; Tan, Y.; Li, H. Role of CYP3A in regulating hepatic clearance and hepatotoxicity of triptolide in rat liver microsomes and sandwich-cultured hepatocytes. Food Chem. Toxicol., 2014, 71, 90-96.
Li, W.; Liu, Y.; He, Y.Q.; Zhang, J.W.; Gao, Y.; Ge, G.B.; Liu, H.X.; Huo, H.; Liu, H.T.; Wang, L.M.; Sun, J.; Wang, Q.; Yang, L. Characterization of triptolide hydroxylation by cytochrome P450 in human and rat liver microsomes. Xenobiotica, 2008, 38(12), 1551-1565.
Liu, J.; Zhou, X.; Chen, X.Y.; Zhong, D.F. Excretion of [3H] triptolide and its metabolites in rats after oral administration. Acta Pharmacol. Sin., 2014, 35(4), 549-554.
Liu, J.; Li, L.; Zhou, X.; Chen, X.; Huang, H.; Zhao, S.; Li, X.; Zhong, D. Metabolite profiling and identification of triptolide in rats. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2013, 939, 51-58.
Du, F.; Liu, T.; Liu, T.; Wang, Y.; Wan, Y.; Xing, J. Metabolite identification of triptolide by data-dependent accurate mass spectrometric analysis in combination with online hydrogen/deuterium exchange and multiple data-mining techniques. Rapid Commun. Mass Spectrom., 2011, 25(20), 3167-3177.
Du, F.; Liu, Z.; Li, X.; Xing, J. Metabolic pathways leading to detoxification of triptolide, a major active component of the herbal medicine Tripterygium wilfordii. J. Appl. Toxicol., 2014, 34(8), 878-884.
Jiang, Z.; Huang, X.; Huang, S.; Guo, H.; Wang, L.; Li, X.; Huang, X.; Wang, T.; Zhang, L.; Sun, L. Sex-related differences of lipid metabolism induced by triptolide: The possible role of the lxralpha/srebp-1 signaling pathway. Front. Pharmacol., 2016, 7, 87.
Ni, B.; Jiang, Z.; Huang, X.; Xu, F.; Zhang, R.; Zhang, Z.; Tian, Y.; Wang, T.; Zhu, T.; Liu, J.; Zhang, L. Male reproductive toxicity and toxicokinetics of triptolide in rats. Arzneimittelforschung, 2008, 58(12), 673-680.
Xue, M.; Zhao, Y.; Li, X.J.; Jiang, Z.Z.; Zhang, L.; Liu, S.H.; Li, X.M.; Zhang, L.Y.; Yang, S.Y. Comparison of toxicokinetic and tissue distribution of triptolide-loaded solid lipid nanoparticles vs free triptolide in rats. Eur. J. Pharm. Sci., 2012, 47(4), 713-717.
Zhang, Y.; Li, J.; Lei, X.; Zhang, T.; Liu, G.; Yang, M.; Liu, M. Influence of Verapamil on Pharmacokinetics of Triptolide in Rats. Eur. J. Drug Metab. Pharmacokinet., 2016, 41(4), 449-456.
Ni, B.; Jiang, Z.; Huang, X.; Xu, F.; Zhang, R.; Zhang, Z.; Tian, Y.; Wang, T.; Zhu, T.; Liu, J. Male reproductive toxicity and toxicokinetics of triptolide in rats. Arzneimittelforschung, 2008, 58(12), 673-680.
Liu, L.; Zhang, J.; Wang, Z.; Xu, D.; Jiang, Z.; Wang, T.; Ju, W.; Zhang, L. Gender Differences in the Toxicokinetics of Triptolide after Single- and Multiple-dose Administration in Rats. Drug Res. (Stuttg.), 2015, 65(11), 602-606.
Liu, L.; Jiang, Z.; Liu, J.; Huang, X.; Wang, T.; Liu, J.; Zhang, Y.; Zhou, Z.; Guo, J.; Yang, L.; Chen, Y.; Zhang, L. Sex differences in subacute toxicity and hepatic microsomal metabolism of triptolide in rats. Toxicology, 2010, 271(1-2), 57-63.
Ma, X.P. Z.H.; Han, F.M.; Chen, Y. Inhibitory effects of triptolide on rat CYP450 enzymes and the metabolic interaction with glycyrrhetinic acid in vitro. Zhonghua Zhongyiyao Zazhi, 2013, 8(3), 691-694.
Tai, T.; Huang, X.; Su, Y.; Ji, J.; Su, Y.; Jiang, Z.; Zhang, L. Glycyrrhizin accelerates the metabolism of triptolide through induction of CYP3A in rats. J. Ethnopharmacol., 2014, 152(2), 358-363.
Xu, Y.; Zhang, Y.F.; Chen, X.Y.; Zhong, D.F. CYP3A4 inducer and inhibitor strongly affect the pharmacokinetics of triptolide and its derivative in rats. Acta Pharmacol. Sin., 2018, 39(8), 1386-1392.
Xue, X.; Gong, L.; Qi, X.; Wu, Y.; Xing, G.; Yao, J.; Luan, Y.; Xiao, Y.; Li, Y.; Wu, X.; Chen, M.; Gu, J.; Ren, J. Knockout of hepatic P450 reductase aggravates triptolide-induced toxicity. Toxicol. Lett., 2011, 205(1), 47-54.
Jia, Y.; Liu, J.; Xu, J. Influence of grapefruit juice on pharmacokinetics of triptolide in rats grapefruit juice on the effects of triptolide. Xenobiotica, 2018, 48(4), 407-411.
Ye, X.; Li, W.; Yan, Y.; Mao, C.; Cai, R.; Xu, H.; Yang, X. Effects of cytochrome P4503A inducer dexamethasone on the metabolism and toxicity of triptolide in rat. Toxicol. Lett., 2010, 192(2), 212-220.
Li, Z.; Yan, M.; Cao, L.; Fang, P.; Guo, Z.; Hou, Z.; Zhang, B. Glycyrrhetinic acid accelerates the clearance of triptolide through P-gp in vitro. Phytother. Res., 2017, 31(7), 1090-1096.
Han, F.M.; Peng, Z.H.; Wang, J.J.; Chen, Y. In vivo effect of triptolide combined with glycyrrhetinic acid on rat cytochrome P450 enzymes. Yao Xue Xue Bao, 2013, 48(7), 1136-1141.
Yang, G.; Wang, L.; Yu, X.; Huang, Y.; Qu, C.; Zhang, Z.; Luo, D.; Lin, J.; Zhou, L.; Su, Z.; Zhang, X.; Chen, H. Protective effect of 18beta-glycyrrhetinic acid against triptolide-induced hepatotoxicity in rats. Evid. Based Complement. Alternat. Med., 2017, 2017, 3470320.
Zhang, H.; Ya, G.; Rui, H. Inhibitory effects of triptolide on human liver cytochrome p450 enzymes and p-glycoprotein. Eur. J. Drug Metab. Pharmacokinet., 2017, 42(1), 89-98.
Wang, X.; Zhang, X.; Liu, F.; Wang, M.; Qin, S. The effects of triptolide on the pharmacokinetics of sorafenib in rats and its potential mechanism. Pharm. Biol., 2017, 55(1), 1863-1867.
Zhang, X.F.; Liu, J.; Ye, F.; Ji, S.G.; Zhang, N.; Cao, R.S.; He, L.; Wu, J.C.; Li, X.F. Effects of triptolide on the pharmacokinetics of cyclophosphamide in rats: A possible role of cytochrome P3A4 inhibition. Chin. J. Integr. Med., 2014, 20(7), 534-539.
Zhuang, X.M.; Shen, G.L.; Xiao, W.B.; Tan, Y.; Lu, C.; Li, H. Assessment of the roles of P-glycoprotein and cytochrome P450 in triptolide-induced liver toxicity in sandwich-cultured rat hepatocyte model. Drug Metab. Dispos., 2013, 41(12), 2158-2165.
Gao, X.; Zhang, Y.; Wang, Y.; Zhang, Y.; Wang, Y.; Liu, S.; Gao, X. Influence of verapamil on pharmacokinetics of pristimerin in rats. Biomed. Chromatogr., 2016, 30(6), 802-809.
Li, C.; Xing, G.; Maeda, K.; Wu, C.; Gong, L.; Sugiyama, Y.; Qi, X.; Ren, J.; Wang, G. The role of breast cancer resistance protein (Bcrp/Abcg2) in triptolide-induced testis toxicity. Toxicol. Res., 2015, 4(5), 1260-1268.
Li, X.; Mao, Y.; Li, K.; Shi, T.; Yao, H.; Yao, J.; Wang, S. Pharmacokinetics and tissue distribution study in mice of triptolide-loaded lipid emulsion and accumulation effect on pancreas. Drug Deliv., 2016, 23(4), 1344-1354.
Zhang, C.; Peng, F.; Liu, W.; Wan, J.; Wan, C.; Xu, H.; Lam, C.W.; Yang, X. Nanostructured lipid carriers as a novel oral delivery system for triptolide: Induced changes in pharmacokinetics profile associated with reduced toxicity in male rats. Int. J. Nanomedicine, 2014, 9, 1049-1063.
Chen, G.; Hao, B.; Ju, D.; Liu, M.; Zhao, H.; Du, Z.; Xia, J. Pharmacokinetic and pharmacodynamic study of triptolide-loaded liposome hydrogel patch under microneedles on rats with collagen-induced arthritis. Acta Pharm. Sin. B, 2015, 5(6), 569-576.
Ling, D.; Xia, H.; Park, W.; Hackett, M.J.; Song, C.; Na, K.; Hui, K.M.; Hyeon, T. pH-sensitive nanoformulated triptolide as a targeted therapeutic strategy for hepatocellular carcinoma. ACS Nano, 2014, 8(8), 8027-8039.
Zhou, P.; Sun, X.; Gong, T.; Zhang, Z.; Zhang, L. Conjugating glucosamine to triptolide to enhance its protective effect against renal ischemia-reperfusion injury and reduce its toxicity. J. Drug Target., 2014, 22(3), 200-210.
Qi, B.; Wang, X.; Zhou, Y.; Han, Q.; He, L.; Gong, T.; Sun, X.; Fu, Y.; Zhang, Z. A renal-targeted Triptolide Aminoglycoside (TPAG) conjugate for lowering systemic toxicities of triptolide. Fitoterapia, 2015, 103, 242-251.
Yuan, Z.X.; Wu, X.J.; Mo, J.; Wang, Y.L.; Xu, C.Q.; Lim, L.Y. Renal targeted delivery of triptolide by conjugation to the fragment peptide of human serum albumin. Eur. J. Pharm. Biopharm., 2015, 94, 363-371.
Fidler, J.M.; Li, K.; Chung, C.; Wei, K.; Ross, J.A.; Gao, M.; Rosen, G.D. PG490-88, a derivative of triptolide, causes tumor regression and sensitizes tumors to chemotherapy. Mol. Cancer Ther., 2003, 2(9), 855-862.
Patil, S.; Lis, L.G.; Schumacher, R.J.; Norris, B.J.; Morgan, M.L.; Cuellar, R.A.; Blazar, B.R.; Suryanarayanan, R.; Gurvich, V.J.; Georg, G.I. Phosphonooxymethyl prodrug of triptolide: Synthesis, physicochemical characterization, and efficacy in human colon adenocarcinoma and ovarian cancer xenografts. J. Med. Chem., 2015, 58(23), 9334-9344.
He, Q.L.; Minn, I.; Wang, Q.; Xu, P.; Head, S.A.; Datan, E.; Yu, B.; Pomper, M.G.; Liu, J.O. Targeted delivery and sustained antitumor activity of triptolide through glucose conjugation. Angew. Chem., 2016, 128(39), 12214-12218.

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Year: 2019
Page: [147 - 154]
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DOI: 10.2174/1389200219666180816141506
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