Generic placeholder image

Current Topics in Medicinal Chemistry


ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Review Article

Berberine: A Promising Natural Isoquinoline Alkaloid for the Development of Hypolipidemic Drugs

Author(s): Dong-Dong Li, Pan Yu, Wei Xiao*, Zhen-Zhong Wang* and Lin-Guo Zhao*

Volume 20, Issue 28, 2020

Page: [2634 - 2647] Pages: 14

DOI: 10.2174/1568026620666200908165913

Price: $65


Berberine, as a representative isoquinoline alkaloid, exhibits significant hypolipidemic activity in both animal models and clinical trials. Recently, a large number of studies on the lipid-lowering mechanism of berberine and studies for improving its hypolipidemic activity have been reported, but for the most part, they have been either incomplete or not comprehensive. In addition, there have been a few specific reviews on the lipid-reducing effect of berberine. In this paper, the physicochemical properties, the lipid-lowering mechanism, and studies of the modification of berberine all are discussed to promote the development of berberine as a lipid-lowering agent. Subsequently, this paper provides some insights into the deficiencies of berberine in the study of lipid-lowering drug, and based on the situation, some proposals are put forward.

Keywords: Berberine, Hypolipidemic activity, Physicochemical property, Cholesterol, Triglyceride, Bioavailability, Chemical modification.

« Previous
Graphical Abstract
Lin, Y.; Guo, H.C.; Kuang, Y.; Shang, Z.P.; Li, B.; Chen, K.; Xu, L.L.; Qiao, X.; Liang, H.; Ye, M. AChE inhibitory alkaloids from Coptis chinensis. Fitoterapia, 2020, 141104464
[] [PMID: 31870946]
Chrzanowska, M.; Rozwadowska, M.D. Asymmetric synthesis of isoquinoline alkaloids. Chem. Rev., 2004, 104(7), 3341-3370.
[] [PMID: 15250744]
Bentley, K.W. beta-Phenylethylamines and the isoquinoline alkaloids. Nat. Prod. Rep., 2006, 23(3), 444-463.
[] [PMID: 16741588]
Kupchan, S.M.; Liepa, A.J. Intramolecular oxidative coupling of monophenolic benzylisoquinolines. Quinonoid oxoaporphines. J. Am. Chem. Soc., 1973, 95(12), 4062-4064.
[] [PMID: 4710068]
Li, T.K.; Bathory, E.; LaVoie, E.J.; Srinivasan, A.R.; Olson, W.K.; Sauers, R.R.; Liu, L.F.; Pilch, D.S. Human topoisomerase I poisoning by protoberberines: potential roles for both drug-DNA and drug-enzyme interactions. Biochemistry, 2000, 39(24), 7107-7116.
[] [PMID: 10852708]
Ma, L.; Seidel, D. Intramolecular redox-mannich reactions: facile access to the tetrahydroprotoberberine core. Chemistry, 2015, 21(37), 12908-12913.
[] [PMID: 26220197]
Zhou, S.; Tong, R.; General, A. A general, concise strategy that enables collective total syntheses of over 50 protoberberine and five aporhoeadane alkaloids within four to eight steps. Chemistry, 2016, 22(21), 7084-7089.
[] [PMID: 26990887]
Reddy, V.; Jadhav, A.S.; Vijaya Anand, R. A room-temperature protocol to access isoquinolines through Ag(I) catalysed annulation of o-(1-alkynyl)arylaldehydes and ketones with NH4OAc: elaboration to berberine and palmatine. Org. Biomol. Chem., 2015, 13(12), 3732-3741.
[] [PMID: 25687222]
Mengozzi, L.; Gualandi, A.; Cozzi, P.G. A highly enantioselective acyl-Mannich reaction of isoquinolines with aldehydes promoted by proline derivatives: an approach to 13-alkyl-tetrahydroprotoberberine alkaloids. Chem. Sci. (Camb.), 2014, 5(10), 3915-3921.
Tillhon, M.; Guamán Ortiz, L.M.; Lombardi, P.; Scovassi, A.I. Berberine: new perspectives for old remedies. Biochem. Pharmacol., 2012, 84(10), 1260-1267.
[] [PMID: 22842630]
Kumar, A. Ekavali; Chopra, K.; Mukherjee, M.; Pottabathini, R.; Dhull, D.K. Current knowledge and pharmacological profile of berberine: An update. Eur. J. Pharmacol., 2015, 761, 288-297.
[] [PMID: 26092760]
Díaz, M.S.; Freile, M.L.; Gutiérrez, M.I. Solvent effect on the UV/Vis absorption and fluorescence spectroscopic properties of berberine. Photochem. Photobiol. Sci., 2009, 8(7), 970-974.
[] [PMID: 19582272]
Cheng, Z.; Dong, H.; Liang, J.; Zhang, F.; Chen, X.; Du, L.; Tan, K. Highly selective fluorescent visual detection of perfluorooctane sulfonate via blue fluorescent carbon dots and berberine chloride hydrate. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2019, 207, 262-269.
[] [PMID: 30253323]
Roy, B.; Hazra, P. Isoquinoline based alkaloid chemosensor for detection of alkanes and subsequent fluorescence switching inside surfactant coated bio-mimicking nanocavity. J. Mol. Liq., 2018, 261, 520-529.
Soulié, M.; Carayon, C.; Saffon, N.; Blanc, S.; Fery-Forgues, S. A comparative study of nine berberine salts in the solid state: optimization of the photoluminescence and self-association properties through the choice of the anion. Phys. Chem. Chem. Phys., 2016, 18(43), 29999-30008.
[] [PMID: 27774564]
Moreno-Guerrero, A.J.; Gómez-García, G.; López-Belmonte, J.; Rodríguez-Jiménez, C. Internet addiction in the web of science database: a review of the literature with scientific mapping. Int. J. Environ. Res. Public Health, 2020, 17(8)E2753
[] [PMID: 32316177]
Liu, X.; Fan, X.; Matsumoto, H.; Nie, Y.; Sha, Z.; Yi, K.; Pan, J.; Qian, Y.; Cao, M.; Wang, Y.; Zhu, G.; Wang, M. Biotoxin tropolone contamination associated with nationwide occurrence of pathogen burkholderia plantarii in agricultural environments in China. Environ. Sci. Technol., 2018, 52(9), 5105-5114.
[] [PMID: 29589436]
Xin, T.; Zhang, Y.; Pu, X.; Gao, R.; Xu, Z.; Song, J. Trends in herbgenomics. Sci. China Life Sci., 2019, 62(3), 288-308.
[] [PMID: 30128965]
Grycová, L.; Dostál, J.; Marek, R. Quaternary protoberberine alkaloids. Phytochemistry, 2007, 68(2), 150-175.
[] [PMID: 17109902]
Guan, X.; Zheng, X.; Vong, C.T.; Zhao, J.; Xiao, J.; Wang, Y.; Zhong, Z. Combined effects of berberine and evodiamine on colorectal cancer cells and cardiomyocytes in vitro. Eur. J. Pharmacol., 2020, 875173031
Wang, B.; Deng, A.J.; Li, Z.H.; Wang, N.; Qin, H.L. Syntheses and structure-activity relationships in growth inhibition activity against human cancer cell lines of 12 substituted berberine derivatives. Molecules, 2020, 25(8)E1871
[] [PMID: 32325679]
Tong, M.; Liu, H.; Hao, J.; Fan, D. Comparative pharmacoproteomics reveals potential targets for berberine, a promising therapy for colorectal cancer. Biochem. Biophys. Res. Commun., 2020, 525(1), 244-250.
[] [PMID: 32087971]
Du, P.; Yan, J.; Long, S.; Xiong, H.; Wen, N.; Cai, S.; Wang, Y.; Peng, D.; Liu, Z.; Liu, Y. Tumor microenvironment and NIR laser dual-responsive release of berberine 9-O-pyrazole alkyl derivative loaded in graphene oxide nanosheets for chemo-photothermal synergetic cancer therapy. J. Mater. Chem. B Mater. Biol. Med., 2020, 8(18), 4046-4055.
[] [PMID: 32248212]
Liu, Y.; Hua, W.; Li, Y.; Xian, X.; Zhao, Z.; Liu, C.; Zou, J.; Li, J.; Fang, X.; Zhu, Y. Berberine suppresses colon cancer cell proliferation by inhibiting the SCAP/SREBP-1 signaling pathway-mediated lipogenesis. Biochem. Pharmacol., 2020, 174113776
Liu, H.; You, L.; Wu, J.; Zhao, M.; Guo, R.; Zhang, H.; Su, R.; Mao, Q.; Deng, D.; Hao, Y. Berberine suppresses influenza virus-triggered NLRP3 inflammasome activation in macrophages by inducing mitophagy and decreasing mitochondrial ROS. J. Leukoc. Biol., 2020, 108(1), 253-266.
[] [PMID: 32272506]
Fan, X.; Xu, M.; Leung, E.L.; Jun, C.; Yuan, Z.; Liu, L. ROS-responsive berberine polymeric micelles effectively suppressed the inflammation of rheumatoid arthritis by targeting mitochondria. Nano-Micro Lett., 2020, 12(761)
Song, J.; Wu, Q.; Jiang, J.; Sun, D.; Wang, F.; Xin, B.; Cui, Q. Berberine reduces inflammation of human dental pulp fibroblast via miR-21/KBTBD7 axis. Arch. Oral Biol., 2020, 110104630
Zhang, B.; Wang, L.; Ji, X.; Zhang, S.; Sik, A.; Liu, K.; Jin, M. Anti-inflammation associated protective mechanism of berberine and its derivatives on attenuating pentylenetetrazole-induced seizures in zebrafish. J. Neuroimmune Pharmacol., 2020, 15(2), 309-325.
[] [PMID: 31909440]
Wang, Y.; Zhou, X.; Zhao, D.; Wang, X.; Gurley, E.C.; Liu, R.; Li, X.; Hylemon, P.B.; Chen, W.; Zhou, H. Berberine inhibits free fatty acid and LPS-induced inflammation via modulating ER stress response in macrophages and hepatocytes. PLoS One, 2020, 15(5)e0232630
[] [PMID: 32357187]
Luganini, A.; Mercorelli, B.; Messa, L.; Palu, G.; Gribaudo, G.; Loregian, A. The isoquinoline alkaloid berberine inhibits human cytomegalovirus replication by interfering with the viral Immediate Early-2 (IE2) protein transactivating activity. Antiviral Res., 2019, 164, 52-60.
Hung, T.C.; Jassey, A.; Liu, C.H.; Lin, C.J.; Lin, C.C.; Wong, S.H.; Wang, J.Y.; Yen, M.H.; Lin, L.T. Berberine inhibits hepatitis C virus entry by targeting the viral E2 glycoprotein. Phytomedicine, 2019, 53, 62-69.
Yan, Y.Q.; Fu, Y.J.; Wu, S.; Qin, H.Q.; Zhen, X.; Song, B.M.; Weng, Y.S.; Wang, P.C.; Chen, X.Y.; Jiang, Z.Y. Anti-influenza activity of berberine improves prognosis by reducing viral replication in mice. Phytother. Res., 2018, 32(12), 2560-2567.
[] [PMID: 30306659]
Varghese, F.S.; Kaukinen, P.; Glasker, S.; Bespalov, M.; Hanski, L.; Wennerberg, K.; Kummerer, B.M.; Ahola, T. Discovery of berberine, abamectin and ivermectin as antivirals against chikungunya and other alphaviruses. Antiviral Res., 2016, 126, 117-124.
Liu, M.; Zhu, D.; Wen, J.; Ding, W.; Huang, S.; Xia, C.; Zhang, H.; Xiong, Y. Berberine promotes oatp1b1 expression and rosuvastatin uptake by inducing nuclear translocation of fxr and lxr alpha. Front. Pharmacol., 2020, 11(375)
Cheng, Z.; Liu, S.; Wu, X.; Raza, F.; Li, Y.; Yuan, W.; Qiu, M.; Su, J. Autologous erythrocytes delivery of berberine hydrochloride with long-acting effect for hypolipidemia treatment. Drug Deliv., 2020, 27(1), 283-291.
[] [PMID: 32013620]
Zhu, X.; Yang, J.; Zhu, W.; Yin, X.; Yang, B.; Wei, Y.; Guo, X. Combination of berberine with resveratrol improves the lipid-lowering efficacy. Int. J. Mol. Sci., 2018, 19(12)E3903
[] [PMID: 30563192]
Yu, P.; Li, D.; Ni, J.; Zhao, L.; Ding, G.; Wang, Z.; Xiao, W. Predictive QSAR modeling study on berberine derivatives with hypolipidemic activity. Chem. Biol. Drug Des., 2018, 91(4), 867-873.
[] [PMID: 29143468]
Jia, Y.; Xu, B.; Xu, J. Effects of type 2 diabetes mellitus on the pharmacokinetics of berberine in rats. Pharm. Biol., 2017, 55(1), 510-515.
[] [PMID: 27937081]
Sato, H.; Taguchi, G.; Fukui, H.; Tabata, M. Role of malic acid in solubilizing excess berberine accumulating in vacuoles of Coptis japonica. Phytochemistry, 1992, 31(10), 3451-3454.
Battu, S.K.; Repka, M.A.; Maddineni, S.; Chittiboyina, A.G.; Avery, M.A.; Majumdar, S. Physicochemical characterization of berberine chloride: a perspective in the development of a solution dosage form for oral delivery. AAPS PharmSciTech, 2010, 11(3), 1466-1475.
[] [PMID: 20842541]
Lu, Y.C.; Lin, Q.; Luo, G.S.; Dai, Y.Y. Solubility of berberine chloride in various solvents. J. Chem. Eng. Data, 2006, 51(2), 642-644.
Chen, W.; Miao, Y.Q.; Fan, D.J.; Yang, S.S.; Lin, X.; Meng, L.K.; Tang, X. Bioavailability study of berberine and the enhancing effects of TPGS on intestinal absorption in rats. AAPS PharmSciTech, 2011, 12(2), 705-711.
[] [PMID: 21637946]
Liu, Y.T.; Hao, H.P.; Xie, H.G.; Lai, L.; Wang, Q.; Liu, C.X.; Wang, G.J. Extensive intestinal first-pass elimination and predominant hepatic distribution of berberine explain its low plasma levels in rats. Drug Metab. Dispos., 2010, 38(10), 1779-1784.
[] [PMID: 20634337]
Chen, Z.; Ye, X.; Yi, J.; Chen, X.; Li, X. Synthesis of 9-O-glycosyl-berberine derivatives and bioavailability evaluation. Med. Chem. Res., 2012, 21(8), 1641-1646.
Wang, A.; Yang, W.; Yang, X.; Mei, X.; Hu, T.; Liang, R.; Meng, D.; Yan, D. MgAl monolayer hydrotalcite increases the hypoglycemic effect of berberine by enhancing its oral bioavailability. Biomed. Pharmacother., 2020, 127110140
Laudadio, E.; Cedraro, N.; Mangiaterra, G.; Citterio, B.; Mobbili, G.; Minnelli, C.; Bizzaro, D.; Biavasco, F.; Galeazzi, R. Natural alkaloid berberine activity against pseudomonas aeruginosa mexxy-mediated aminoglycoside resistance: in silico and in vitro studies. J. Nat. Prod., 2019, 82(7), 1935-1944.
[] [PMID: 31274312]
Ju, J.; Li, J.; Lin, Q.; Xu, H. Efficacy and safety of berberine for dyslipidaemias: A systematic review and meta-analysis of randomized clinical trials. Phytomedicine, 2018, 50, 25-34.
[] [PMID: 30466986]
Belanova, A.; Beseda, D.; Chmykhalo, V.; Stepanova, A.; Belousova, M.; Khrenkova, V.; Gavalas, N.; Zolotukhin, P. Berberine effects on nfκb, hif1a and nfe2l2/ap-1 pathways in hela cells. Anticancer. Agents Med. Chem., 2019, 19(4), 487-501.
[] [PMID: 30526471]
Kheir, M.M.; Wang, Y.; Hua, L.; Hu, J.; Li, L.; Lei, F.; Du, L. Acute toxicity of berberine and its correlation with the blood concentration in mice. Food Chem. Toxicol., 2010, 48(4), 1105-1110.
[] [PMID: 20138204]
Feng, P.; Zhao, L.; Guo, F.; Zhang, B.; Fang, L.; Zhan, G.; Xu, X.; Fang, Q.; Liang, Z.; Li, B. The enhancement of cardiotoxicity that results from inhibiton of CYP 3A4 activity and hERG channel by berberine in combination with statins. Chem. Biol. Interact., 2018, 293, 115-123.
[] [PMID: 30086269]
Kysenius, K.; Brunello, C.A.; Huttunen, H.J. Mitochondria and NMDA receptor-dependent toxicity of berberine sensitizes neurons to glutamate and rotenone injury. PLoS One, 2014, 9(9)e107129
[] [PMID: 25192195]
Wang, L.; Kong, H.; Jin, M.; Li, X.; Stoika, R.; Lin, H.; Liu, K. Synthesis of disaccharide modified berberine derivatives and their anti-diabetic investigation in zebrafish using a fluorescence-based technology. Org. Biomol. Chem., 2020, 18(18), 3563-3574.
[] [PMID: 32347284]
Li, Y.; Zhu, C. Development and in vitro and in vivo evaluation of microspheres containing sodium n-[8-(2-hydroxybenzoyl)amino]caprylate for the oral delivery of berberine hydrochloride. Molecules, 2020, 25(8)E1957
[] [PMID: 32340157]
Zhang, M.; Zhang, Y.; Xiao, D.; Zhang, J.; Wang, X.; Guan, F.; Zhang, M.; Chen, L. Highly bioavailable berberine formulation ameliorates diabetic nephropathy through the inhibition of glomerular mesangial matrix expansion and the activation of autophagy. Eur. J. Pharmacol., 2020, 873172955
[] [PMID: 32001218]
Zuo, F.; Nakamura, N.; Akao, T.; Hattori, M. Pharmacokinetics of berberine and its main metabolites in conventional and pseudo germ-free rats determined by liquid chromatography/ion trap mass spectrometry. Drug Metab. Dispos., 2006, 34(12), 2064-2072.
[] [PMID: 16956957]
Ikekawa, T.; Ikeda, Y. Antitumor activity of 13-methyl-berberrubine derivatives. J. Pharmacobiodyn., 1982, 5(7), 469-474.
[] [PMID: 7131231]
Saha, U.; Yasmeen Khan, A.; Bhuiya, S.; Das, S.; Fiorillo, G.; Lombardi, P.; Suresh Kumar, G. Targeting human telomeric DNA quadruplex with novel berberrubine derivatives: insights from spectroscopic and docking studies. J. Biomol. Struct. Dyn., 2019, 37(6), 1375-1389.
[] [PMID: 29607778]
Porru, E.; Franco, P.; Calabria, D.; Spinozzi, S.; Roberti, M.; Caliceti, C.; Roda, A. Combined analytical approaches to define biodistribution and biological activity of semi-synthetic berberrubine, the active metabolite of natural berberine. Anal. Bioanal. Chem., 2018, 410(15), 3533-3545.
[] [PMID: 29411090]
Li, R.; Wu, J.; He, Y.; Hai, L.; Wu, Y. Synthesis and in vitro evaluation of 12-(substituted aminomethyl) berberrubine derivatives as anti-diabetics. Bioorg. Med. Chem. Lett., 2014, 24(7), 1762-1765.
[] [PMID: 24613165]
Park, K.D.; Lee, J.H.; Kim, S.H.; Kang, T.H.; Moon, J.S.; Kim, S.U. Synthesis of 13-(substituted benzyl) berberine and berberrubine derivatives as antifungal agents. Bioorg. Med. Chem. Lett., 2006, 16(15), 3913-3916.
[] [PMID: 16730982]
Spinozzi, S.; Colliva, C.; Camborata, C.; Roberti, M.; Ianni, C.; Neri, F.; Calvarese, C.; Lisotti, A.; Mazzella, G.; Roda, A. Berberine and its metabolites: relationship between physicochemical properties and plasma levels after administration to human subjects. J. Nat. Prod., 2014, 77(4), 766-772.
[] [PMID: 24593257]
Avdeef, A. Physicochemical profiling (solubility, permeability and charge state). Curr. Top. Med. Chem., 2001, 1(4), 277-351.
[] [PMID: 11899112]
Lan, J.; Zhao, Y.; Dong, F.; Yan, Z.; Zheng, W.; Fan, J.; Sun, G. Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension. J. Ethnopharmacol., 2015, 161, 69-81.
[] [PMID: 25498346]
Pirillo, A.; Catapano, A.L. Berberine, a plant alkaloid with lipid- and glucose-lowering properties: From in vitro evidence to clinical studies. Atherosclerosis, 2015, 243(2), 449-461.
[] [PMID: 26520899]
Yuan, Z.Y.; Wang, Y.G.; Chai, Y.S.; Hu, J.; Jiang, J.F.; Yan, X.J.; Du, L.J. Berberine action targets and its absorption behavior:how to use old drug for new mechanisms. Zhongguo Zhongyao Zazhi, 2016, 41(12), 2362-2370.
[PMID: 28901086]
DeFronzo, R.A.; Ferrannini, E. Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care, 1991, 14(3), 173-194.
[] [PMID: 2044434]
Frick, M.H.; Elo, O.; Haapa, K.; Heinonen, O.P.; Heinsalmi, P.; Helo, P.; Huttunen, J.K.; Kaitaniemi, P.; Koskinen, P.; Manninen, V.; Et, A. Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N. Engl. J. Med., 1987, 317(20), 1237-1245.
[] [PMID: 3313041]
Imanshahidi, M.; Hosseinzadeh, H. Pharmacological and therapeutic effects of Berberis vulgaris and its active constituent, berberine. Phytother. Res., 2008, 22(8), 999-1012.
[] [PMID: 18618524]
Yao, J.; Kong, W.; Jiang, J. Learning from berberine: Treating chronic diseases through multiple targets. Sci. China Life Sci., 2015, 58(9), 854-859.
[] [PMID: 24174332]
Chowdhury, J.R.; Grossman, M.; Gupta, S.; Chowdhury, N.R.; Baker, J.R., Jr; Wilson, J.M. Long-term improvement of hypercholesterolemia after ex vivo gene therapy in LDLR-deficient rabbits. Science, 1991, 254(5039), 1802-1805.
[] [PMID: 1722351]
Hardie, D.G.; Ross, F.A.; Hawley, S.A. AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat. Rev. Mol. Cell Biol., 2012, 13(4), 251-262.
[] [PMID: 22436748]
Yin, J.; Xing, H.; Ye, J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism, 2008, 57(5), 712-717.
[] [PMID: 18442638]
Zhang, Y.; Li, X.; Zou, D.; Liu, W.; Yang, J.; Zhu, N.; Huo, L.; Wang, M.; Hong, J.; Wu, P.; Ren, G.; Ning, G. Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. J. Clin. Endocrinol. Metab., 2008, 93(7), 2559-2565.
[] [PMID: 18397984]
Lau, C.W.; Yao, X.Q.; Chen, Z.Y.; Ko, W.H.; Huang, Y. Cardiovascular actions of berberine. Cardiovasc. Drug Rev., 2001, 19(3), 234-244.
[] [PMID: 11607041]
Sanders, M.J.; Grondin, P.O.; Hegarty, B.D.; Snowden, M.A.; Carling, D. Investigating the mechanism for AMP activation of the AMP-activated protein kinase cascade. Biochem. J., 2007, 403(1), 139-148.
[] [PMID: 17147517]
Turner, N.; Li, J.Y.; Gosby, A.; To, S.W.; Cheng, Z.; Miyoshi, H.; Taketo, M.M.; Cooney, G.J.; Kraegen, E.W.; James, D.E.; Hu, L.H.; Li, J.; Ye, J.M. Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: a mechanism for the action of berberine to activate AMP-activated protein kinase and improve insulin action. Diabetes, 2008, 57(5), 1414-1418.
[] [PMID: 18285556]
Zhang, Z.; Zhang, H.; Li, B.; Meng, X.; Wang, J.; Zhang, Y.; Yao, S.; Ma, Q.; Jin, L.; Yang, J.; Wang, W.; Ning, G. Berberine activates thermogenesis in white and brown adipose tissue. Nat. Commun., 2014, 5, 5493.
[] [PMID: 25423280]
Zhang, Q.; Xiao, X.; Feng, K.; Wang, T.; Li, W.; Yuan, T.; Sun, X.; Sun, Q.; Xiang, H.; Wang, H. Berberine moderates glucose and lipid metabolism through multipathway mechanism. Evid. Based Complement. Alternat. Med., 2011. [epub ahead of print]
Wang, Q.; Zhang, M.; Liang, B.; Shirwany, N.; Zhu, Y.; Zou, M.H. Activation of AMP-activated protein kinase is required for berberine-induced reduction of atherosclerosis in mice: the role of uncoupling protein 2. PLoS One, 2011, 6(9)e25436
[] [PMID: 21980456]
Xue, B.; Kahn, B.B. AMPK integrates nutrient and hormonal signals to regulate food intake and energy balance through effects in the hypothalamus and peripheral tissues. J. Physiol., 2006, 574(Pt 1), 73-83.
[] [PMID: 16709629]
Ruan, H.; Zhan, Y.Y.; Hou, J.; Xu, B.; Chen, B.; Tian, Y.; Wu, D.; Zhao, Y.; Zhang, Y.; Chen, X.; Mi, P.; Zhang, L.; Zhang, S.; Wang, X.; Cao, H.; Zhang, W.; Wang, H.; Li, H.; Su, Y.; Zhang, X.K.; Hu, T. Berberine binds RXRα to suppress β-catenin signaling in colon cancer cells. Oncogene, 2017, 36(50), 6906-6918.
[] [PMID: 28846104]
Inoue, I.; Itoh, F.; Aoyagi, S.; Tazawa, S.; Kusama, H.; Akahane, M.; Mastunaga, T.; Hayashi, K.; Awata, T.; Komoda, T.; Katayama, S. Fibrate and statin synergistically increase the transcriptional activities of PPARalpha/RXRalpha and decrease the transactivation of NFkappaB. Biochem. Biophys. Res. Commun., 2002, 290(1), 131-139.
[] [PMID: 11779144]
Zou, Y.; Du, H.; Yin, M.; Zhang, L.; Mao, L.; Xiao, N.; Ren, G.; Zhang, C.; Pan, J. Effects of high dietary fat and cholesterol on expression of PPAR alpha, LXR alpha, and their responsive genes in the liver of apoE and LDLR double deficient mice. Mol. Cell. Biochem., 2009, 323(1-2), 195-205.
[] [PMID: 19067122]
Jiang, D.; Wang, D.; Zhuang, X.; Wang, Z.; Ni, Y.; Chen, S.; Sun, F. Berberine increases adipose triglyceride lipase in 3T3-L1 adipocytes through the AMPK pathway. Lipids Health Dis., 2016, 15(1), 214.
[] [PMID: 27938388]
Hao, M.; Li, Y.; Liu, L.; Yuan, X.; Gao, Y.; Guan, Z.; Li, W. The design and synthesis of a novel compound of berberine and baicalein that inhibits the efficacy of lipid accumulation in 3T3-L1 adipocytes. Bioorg. Med. Chem., 2017, 25(20), 5506-5512.
[] [PMID: 28818460]
Choi, B.H.; Ahn, I.S.; Kim, Y.H.; Park, J.W.; Lee, S.Y.; Hyun, C.K.; Do, M.S. Berberine reduces the expression of adipogenic enzymes and inflammatory molecules of 3T3-L1 adipocyte. Exp. Mol. Med., 2006, 38(6), 599-605.
[] [PMID: 17202835]
Xia, X.; Yan, J.; Shen, Y.; Tang, K.; Yin, J.; Zhang, Y.; Yang, D.; Liang, H.; Ye, J.; Weng, J. Berberine improves glucose metabolism in diabetic rats by inhibition of hepatic gluconeogenesis. PLoS One, 2011, 6(2)e16556
[] [PMID: 21304897]
Liu, X.; Li, G.; Zhu, H.; Huang, L.; Liu, Y.; Ma, C.; Qin, C. Beneficial effect of berberine on hepatic insulin resistance in diabetic hamsters possibly involves in SREBPs, LXRα and PPARα transcriptional programs. Endocr. J., 2010, 57(10), 881-893.
[] [PMID: 20724798]
Kanehisa, M.; Goto, S. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res., 2000, 28(1), 27-30.
[] [PMID: 10592173]
Liu, M.; Zhu, D.; Wen, J.; Ding, W.; Huang, S.; Xia, C.; Zhang, H.; Xiong, Y. Berberine promotes oatp1b1 expression and rosuvastatin uptake by inducing nuclear translocation of fxr and lxralpha. Front. Pharmacol., 2020. epub ahead of print
Li, H.; Chen, W.; Zhou, Y.; Abidi, P.; Sharpe, O.; Robinson, W.H.; Kraemer, F.B.; Liu, J. Identification of mRNA binding proteins that regulate the stability of LDL receptor mRNA through AU-rich elements. J. Lipid Res., 2009, 50(5), 820-831.
[] [PMID: 19141871]
Pan, R.; Cai, W.; Sun, J.; Yu, C.; Li, P.; Zheng, M. Inhibition of KHSRP sensitizes colorectal cancer to 5-fluoruracil through miR-501-5p-mediated ERRFI1 mRNA degradation. J. Cell. Physiol., 2020, 235(2), 1576-1587.
[] [PMID: 31313286]
Behm-Ansmant, I.; Gatfield, D.; Rehwinkel, J.; Hilgers, V.; Izaurralde, E. A conserved role for cytoplasmic poly(A)-binding protein 1 (PABPC1) in nonsense-mediated mRNA decay. EMBO J., 2007, 26(6), 1591-1601.
[] [PMID: 17318186]
Yuan, Z.Y.; Lu, X.; Lei, F.; Chai, Y.S.; Wang, Y.G.; Jiang, J.F.; Feng, T.S.; Wang, X.P.; Yu, X.; Yan, X.J.; Xing, D.M.; Du, L.J. TATA boxes in gene transcription and poly (A) tails in mRNA stability: New perspective on the effects of berberine. Sci. Rep., 2015, 5, 18326.
[] [PMID: 26671652]
Wang, Y.; Kheir, M.M.; Chai, Y.; Hu, J.; Xing, D.; Lei, F.; Du, L. Comprehensive study in the inhibitory effect of berberine on gene transcription, including TATA box. PLoS One, 2011, 6(8)e23495
[] [PMID: 21887260]
Kuo, C.L.; Chou, C.C.; Yung, B.Y. Berberine complexes with DNA in the berberine-induced apoptosis in human leukemic HL-60 cells. Cancer Lett., 1995, 93(2), 193-200.
[] [PMID: 7621428]
Li, X.L.; Hu, Y.J.; Wang, H.; Yu, B.Q.; Yue, H.L. Molecular spectroscopy evidence of berberine binding to DNA: comparative binding and thermodynamic profile of intercalation. Biomacromolecules, 2012, 13(3), 873-880.
[] [PMID: 22316074]
Liu, Z.; Liu, Q.; Xu, B.; Wu, J.; Guo, C.; Zhu, F.; Yang, Q.; Gao, G.; Gong, Y.; Shao, C. Berberine induces p53-dependent cell cycle arrest and apoptosis of human osteosarcoma cells by inflicting DNA damage. Mutat. Res., 2009, 662(1-2), 75-83.
[] [PMID: 19159633]
Abidi, P.; Zhou, Y.; Jiang, J.D.; Liu, J. Extracellular signal-regulated kinase-dependent stabilization of hepatic low-density lipoprotein receptor mRNA by herbal medicine berberine. Arterioscler. Thromb. Vasc. Biol., 2005, 25(10), 2170-2176.
[] [PMID: 16100034]
Lee, S.; Lim, H.J.; Park, J.H.; Lee, K.S.; Jang, Y.; Park, H.Y. Berberine-induced LDLR up-regulation involves JNK pathway. Biochem. Biophys. Res. Commun., 2007, 362(4), 853-857.
[] [PMID: 17767919]
Qian, Y.W.; Schmidt, R.J.; Zhang, Y.; Chu, S.; Lin, A.; Wang, H.; Wang, X.; Beyer, T.P.; Bensch, W.R.; Li, W.; Ehsani, M.E.; Lu, D.; Konrad, R.J.; Eacho, P.I.; Moller, D.E.; Karathanasis, S.K.; Cao, G. Secreted PCSK9 downregulates low density lipoprotein receptor through receptor-mediated endocytosis. J. Lipid Res., 2007, 48(7), 1488-1498.
[] [PMID: 17449864]
Zhou, Y.; Cao, S.; Wang, Y.; Xu, P.; Yan, J.; Bin, W.; Qiu, F.; Kang, N. Berberine metabolites could induce low density lipoprotein receptor up-regulation to exert lipid-lowering effects in human hepatoma cells. Fitoterapia, 2014, 92, 230-237.
[] [PMID: 24321576]
Dong, B.; Li, H.; Singh, A.B.; Cao, A.; Liu, J. Inhibition of PCSK9 transcription by berberine involves down-regulation of hepatic HNF1α protein expression through the ubiquitin-proteasome degradation pathway. J. Biol. Chem., 2015, 290(7), 4047-4058.
[] [PMID: 25540198]
Di, D.; Wang, Z.; Liu, Y.; Luo, G.; Shi, Y.; Berggren-Söderlund, M.; Nilsson-Ehle, P.; Zhang, X.; Xu, N. ABCA1 upregulating apolipoproein M expression mediates via the RXR/LXR pathway in HepG2 cells. Biochem. Biophys. Res. Commun., 2012, 421(1), 152-156.
[] [PMID: 22516753]
Schmitz, G.; Langmann, T. Transcriptional regulatory networks in lipid metabolism control ABCA1 expression. Biochim. Biophys. Acta, 2005, 1735(1), 1-19.
[] [PMID: 15922656]
Lee, T.S.; Pan, C.C.; Peng, C.C.; Kou, Y.R.; Chen, C.Y.; Ching, L.C.; Tsai, T.H.; Chen, S.F.; Lyu, P.C.; Shyue, S.K. Anti-atherogenic effect of berberine on LXRalpha-ABCA1-dependent cholesterol efflux in macrophages. J. Cell. Biochem., 2010, 111(1), 104-110.
[] [PMID: 20506155]
Liang, H.; Wang, Y. Berberine alleviates hepatic lipid accumulation by increasing ABCA1 through the protein kinase C δ pathway. Biochem. Biophys. Res. Commun., 2018, 498(3), 473-480.
[] [PMID: 29505790]
Sun, R.; Yang, N.; Kong, B.; Cao, B.; Feng, D.; Yu, X.; Ge, C.; Huang, J.; Shen, J.; Wang, P.; Feng, S.; Fei, F.; Guo, J.; He, J.; Aa, N.; Chen, Q.; Pan, Y.; Schumacher, J.D.; Yang, C.S.; Guo, G.L.; Aa, J.; Wang, G. Orally administered berberine modulates hepatic lipid metabolism by altering microbial bile acid metabolism and the intestinal fxr signaling pathway. Mol. Pharmacol., 2017, 91(2), 110-122.
[] [PMID: 27932556]
Tian, Y.; Cai, J.; Gui, W.; Nichols, R.G.; Koo, I.; Zhang, J.; Anitha, M.; Patterson, A.D. Berberine directly affects the gut microbiota to promote intestinal farnesoid x receptor activation. Drug Metab. Dispos., 2019, 47(2), 86-93.
[] [PMID: 30409838]
Habtemariam, S. Berberine pharmacology and the gut microbiota: A hidden therapeutic link. Pharmacol. Res., 2020, 155104722
[] [PMID: 32105754]
Tremaroli, V.; Bäckhed, F. Functional interactions between the gut microbiota and host metabolism. Nature, 2012, 489(7415), 242-249.
[] [PMID: 22972297]
Nicholson, J.K.; Holmes, E.; Kinross, J.; Burcelin, R.; Gibson, G.; Jia, W.; Pettersson, S. Host-gut microbiota metabolic interactions. Science, 2012, 336(6086), 1262-1267.
[] [PMID: 22674330]
Enright, E.F.; Joyce, S.A.; Gahan, C.G.; Griffin, B.T. Impact of gut microbiota-mediated bile acid metabolism on the solubilization capacity of bile salt micelles and drug solubility. Mol. Pharm., 2017, 14(4), 1251-1263.
[] [PMID: 28186768]
Tilg, H.; Kaser, A. Gut microbiome, obesity, and metabolic dysfunction. J. Clin. Invest., 2011, 121(6), 2126-2132.
[] [PMID: 21633181]
Wang, Y.; Shou, J.W.; Li, X.Y.; Zhao, Z.X.; Fu, J.; He, C.Y.; Feng, R.; Ma, C.; Wen, B.Y.; Guo, F.; Yang, X.Y.; Han, Y.X.; Wang, L.L.; Tong, Q.; You, X.F.; Lin, Y.; Kong, W.J.; Si, S.Y.; Jiang, J.D. Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism. Metabolism, 2017, 70, 72-84.
[] [PMID: 28403947]
Zhang, X.; Zhao, Y.; Xu, J.; Xue, Z.; Zhang, M.; Pang, X.; Zhang, X.; Zhao, L. Modulation of gut microbiota by berberine and metformin during the treatment of high-fat diet-induced obesity in rats. Sci. Rep., 2015, 5, 14405.
[] [PMID: 26396057]
Feng, R.; Shou, J.W.; Zhao, Z.X.; He, C.Y.; Ma, C.; Huang, M.; Fu, J.; Tan, X.S.; Li, X.Y.; Wen, B.Y.; Chen, X.; Yang, X.Y.; Ren, G.; Lin, Y.; Chen, Y.; You, X.F.; Wang, Y.; Jiang, J.D. Transforming berberine into its intestine-absorbable form by the gut microbiota. Sci. Rep., 2015, 5, 12155.
[] [PMID: 26174047]
Liu, C.S.; Zheng, Y.R.; Zhang, Y.F.; Long, X.Y. Research progress on berberine with a special focus on its oral bioavailability. Fitoterapia, 2016, 109, 274-282.
[] [PMID: 26851175]
Almarsson, O.; Zaworotko, M.J. Crystal engineering of the composition of pharmaceutical phases. Do pharmaceutical co-crystals represent a new path to improved medicines? Chem. Commun. (Camb.), 2004, 17(17), 1889-1896.
[] [PMID: 15340589]
Landenberger, K.B.; Bolton, O.; Matzger, A.J. Two isostructural explosive cocrystals with significantly different thermodynamic stabilities. Angew. Chem. Int. Ed. Engl., 2013, 52(25), 6468-6471.
[] [PMID: 23649781]
Bolla, G.; Nangia, A. Pharmaceutical cocrystals: walking the talk. Chem. Commun. (Camb.), 2016, 52(54), 8342-8360.
[] [PMID: 27278109]
Sa, R.; Zhang, Y.; Deng, Y.; Huang, Y.; Zhang, M.; Lou, B. Novel salt cocrystal of chrysin with berberine: preparation, characterization, and oral bioavailability. Cryst. Growth Des., 2018, 18(8), 4724-4730.
Deng, Y.; Zhang, Y.; Huang, Y.; Zhang, M.; Lou, B. Preparation, crystal structures, and oral bioavailability of two cocrystals of emodin with berberine chloride. Cryst. Growth Des., 2018, 18(12), 7481-7488.
Cui, H.X.; Hu, Y.N.; Li, J.W.; Yuan, K.; Guo, Y. Preparation and evaluation of antidiabetic agents of berberine organic acid salts for enhancing the bioavailability. Molecules, 2018, 24(1)E103
[] [PMID: 30597911]
Gu, Z.; Atherton, J.J.; Xu, Z.P. Hierarchical layered double hydroxide nanocomposites: structure, synthesis and applications. Chem. Commun. (Camb.), 2015, 51(15), 3024-3036.
[] [PMID: 25562489]
Mei, X.; Wang, W.; Yan, L.; Hu, T.; Liang, R.; Yan, D.; Wei, M.; Evans, D.G.; Duan, X. Hydrotalcite monolayer toward high performance synergistic dual-modal imaging and cancer therapy. Biomaterials, 2018, 165, 14-24.
[] [PMID: 29500979]
Jia, J.; Zhang, K.; Zhou, X.; Zhou, D.; Ge, F. Precise dissolution control and bioavailability evaluation for insoluble drug berberine via a polymeric particle prepared using supercritical co2. Polymers (Basel), 2018, 10(119811)
Shi, J.; Guo, F.; Zheng, A.; Zhang, X.; Sun, J. Progress in the study of drug nanocrystals. Pharmazie, 2015, 70(12), 757-764.
[PMID: 26817271]
Nagarwal, R.C.; Kumar, R.; Dhanawat, M.; Das, N.; Pandit, J.K. Nanocrystal technology in the delivery of poorly soluble drugs: an overview. Curr. Drug Deliv., 2011, 8(4), 398-406.
[] [PMID: 21453258]
Xiong, W.; Sang, W.; Linghu, K.G.; Zhong, Z.F.; Cheang, W.S.; Li, J.; Hu, Y.J.; Yu, H.; Wang, Y.T. Dual-functional Brij-S20-modified nanocrystal formulation enhances the intestinal transport and oral bioavailability of berberine. Int. J. Nanomedicine, 2018, 13, 3781-3793.
[] [PMID: 29988733]
Elsheikh, M.A.; Elnaggar, Y.S.R.; Hamdy, D.A.; Abdallah, O.Y. Novel cremochylomicrons for improved oral bioavailability of the antineoplastic phytomedicine berberine chloride: Optimization and pharmacokinetics. Int. J. Pharm., 2018, 535(1-2), 316-324.
[] [PMID: 29138046]
Xiao, D.; Liu, Z.; Zhang, S.; Zhou, M.; He, F.; Zou, M.; Peng, J.; Xie, X.; Liu, Y.; Peng, D. Berberine Derivatives with Different Pharmacological Activities via Structural Modifications. Mini Rev. Med. Chem., 2018, 18(17), 1424-1441.
[] [PMID: 28325147]
Yang, Y.; Ye, X.L.; Li, X.G.; Zhen, J.; Zhang, B.; Yuan, L. Synthesis and antimicrobial activity of 8-alkylberberine derivatives with a long aliphatic chain. Planta Med., 2007, 73(6), 602-604.
[] [PMID: 17650546]
Wang, L.J.; Ye, X.L.; Chen, Z.; Li, X.G.; Sun, Q.L.; Zhang, B.S.; Cao, X.G.; Yu, G.; Niu, X.H. Synthesis and antimicrobial activity of 3-octyloxy-8-alkyljatrorrhizine derivatives. J. Asian Nat. Prod. Res., 2009, 11(4), 365-370.
[] [PMID: 19431018]
Liu, Y.X.; Xiao, C.L.; Wang, Y.X.; Li, Y.H.; Yang, Y.H.; Li, Y.B.; Bi, C.W.; Gao, L.M.; Jiang, J.D.; Song, D.Q. Synthesis, structure-activity relationship and in vitro anti-mycobacterial evaluation of 13-n-octylberberine derivatives. Eur. J. Med. Chem., 2012, 52, 151-158.
[] [PMID: 22503208]
Ma, Y.; Ou, T.M.; Tan, J.H.; Hou, J.Q.; Huang, S.L.; Gu, L.Q.; Huang, Z.S. Quinolino-benzo-[5, 6]-dihydroisoquindolium compounds derived from berberine: a new class of highly selective ligands for G-quadruplex DNA in c-myc oncogene. Eur. J. Med. Chem., 2011, 46(5), 1906-1913.
[] [PMID: 21392861]
Lo, C.Y.; Hsu, L.C.; Chen, M.S.; Lin, Y.J.; Chen, L.G.; Kuo, C.D.; Wu, J.Y. Synthesis and anticancer activity of a novel series of 9-O-substituted berberine derivatives: a lipophilic substitute role. Bioorg. Med. Chem. Lett., 2013, 23(1), 305-309.
[] [PMID: 23182088]
Pierpaoli, E.; Damiani, E.; Orlando, F.; Lucarini, G.; Bartozzi, B.; Lombardi, P.; Salvatore, C.; Geroni, C.; Donati, A.; Provinciali, M. Antiangiogenic and antitumor activities of berberine derivative NAX014 compound in a transgenic murine model of HER2/neu-positive mammary carcinoma. Carcinogenesis, 2015, 36(10), 1169-1179.
[] [PMID: 26168818]
Bian, X.; He, L.; Yang, G. Synthesis and antihyperglycemic evaluation of various protoberberine derivatives. Bioorg. Med. Chem. Lett., 2006, 16(5), 1380-1383.
[] [PMID: 16359864]
Zhang, S.; Wang, X.; Yin, W.; Liu, Z.; Zhou, M.; Xiao, D.; Liu, Y.; Peng, D. Synthesis and hypoglycemic activity of 9-O-(lipophilic group substituted) berberine derivatives. Bioorg. Med. Chem. Lett., 2016, 26(19), 4799-4803.
[] [PMID: 27561717]
Wang, Y.X.; Kong, W.J.; Li, Y.H.; Tang, S.; Li, Z.; Li, Y.B.; Shan, Y.Q.; Bi, C.W.; Jiang, J.D.; Song, D.Q. Synthesis and structure-activity relationship of berberine analogues in LDLR up-regulation and AMPK activation. Bioorg. Med. Chem., 2012, 20(22), 6552-6558.
[] [PMID: 23058107]
Li, Y.H.; Li, Y.; Yang, P.; Kong, W.J.; You, X.F.; Ren, G.; Deng, H.B.; Wang, Y.M.; Wang, Y.X.; Jiang, J.D.; Song, D.Q. Design, synthesis, and cholesterol-lowering efficacy for prodrugs of berberrubine. Bioorg. Med. Chem., 2010, 18(17), 6422-6428.
[] [PMID: 20673726]
Cao, S.; Yu, S.; Cheng, L.; Yan, J.; Zhu, Y.; Deng, Y.; Qiu, F.; Kang, N. 9-O-benzoyl-substituted berberine exerts a triglyceride-lowering effect through AMPK signaling pathway in human hepatoma HepG2 cells. Environ. Toxicol. Pharmacol., 2018, 64, 11-17.
[] [PMID: 30268048]
Wang, Y.X.; Wang, Y.P.; Zhang, H.; Kong, W.J.; Li, Y.H.; Liu, F.; Gao, R.M.; Liu, T.; Jiang, J.D.; Song, D.Q. Synthesis and biological evaluation of berberine analogues as novel up-regulators for both low-density-lipoprotein receptor and insulin receptor. Bioorg. Med. Chem. Lett., 2009, 19(21), 6004-6008.
[] [PMID: 19800225]
Nechepurenko, I.V.; Boyarskikh, U.A.; Khvostov, M.V.; Baev, D.S.; Komarova, N.I.; Filipenko, M.L.; Tolstikova, T.G.; Salakhutdinov, N.F. Hypolipidemic berberine derivatives with a reduced aromatic ring c. Chem. Nat. Compd., 2015, 51(5), 916-922.
Li, Y.H.; Yang, P.; Kong, W.J.; Wang, Y.X.; Hu, C.Q.; Zuo, Z.Y.; Wang, Y.M.; Gao, H.; Gao, L.M.; Feng, Y.C.; Du, N.N.; Liu, Y.; Song, D.Q.; Jiang, J.D. Berberine analogues as a novel class of the low-density-lipoprotein receptor up-regulators: synthesis, structure-activity relationships, and cholesterol-lowering efficacy. J. Med. Chem., 2009, 52(2), 492-501.
[] [PMID: 19090767]
Weerapana, E.; Wang, C.; Simon, G.M.; Richter, F.; Khare, S.; Dillon, M.B.; Bachovchin, D.A.; Mowen, K.; Baker, D.; Cravatt, B.F. Quantitative reactivity profiling predicts functional cysteines in proteomes. Nature, 2010, 468(7325), 790-795.
[] [PMID: 21085121]
Jafari, R.; Almqvist, H.; Axelsson, H.; Ignatushchenko, M.; Lundbäck, T.; Nordlund, P.; Martinez Molina, D. The cellular thermal shift assay for evaluating drug target interactions in cells. Nat. Protoc., 2014, 9(9), 2100-2122.
[] [PMID: 25101824]
Winter, G.E.; Buckley, D.L.; Paulk, J.; Roberts, J.M.; Souza, A.; Dhe-Paganon, S.; Bradner, J.E. DRUG DEVELOPMENT. Phthalimide conjugation as a strategy for in vivo target protein degradation. Science, 2015, 348(6241), 1376-1381.
[] [PMID: 25999370]
Li, W.; Gao, C.; Zhao, L.; Yuan, Z.; Chen, Y.; Jiang, Y. Phthalimide conjugations for the degradation of oncogenic PI3K. Eur. J. Med. Chem., 2018, 151, 237-247.
[] [PMID: 29625382]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy