Generic placeholder image

Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Research Article

A Study of the Mechanism of Binding between Neratinib and MAD2L1 Based on Molecular Simulation and Multi-spectroscopy Methods

Author(s): Guangya Zhou, Manman Zhao, Ruirui Liang, Jiayang Xie, Xinyi Chen, Qin Chen*, Linfeng Zheng*, Xin Cao* and Bing Niu*

Volume 25, Issue 40, 2019

Page: [4287 - 4295] Pages: 9

DOI: 10.2174/1381612825666191107102413

Price: $65


Background: Nilatinib is an irreversible tyrosine kinase inhibitor, which is used in the treatment of some kinds of cancer. To study the interaction between Neratinib and MAD2L1, a potential tumor target, is of guiding significance for enriching the medicinal value of Neratinib.

Method: The binding mechanism between Mitotic arrest deficient 2-like protein 1 (MAD2L1) and Neratinib under simulative physiological conditions was investigated by molecule simulation and multi-spectroscopy approaches.

Results: Molecular docking showed the most possible binding mode of Neratinib-MAD2L1 and the potential binding sites and interaction forces of the interaction between MAD2L1 and Neratinib. Fluorescence spectroscopy experiments manifested that Neratinib could interact with MAD2L1 and form a complex by hydrogen bond and van der Waals interaction. These results were consistent with the conclusions obtained from molecular docking. In addition, according to Synchronous fluorescence and three-dimensional fluorescence results, Neratinib might lead to the conformational change of MAD2L1, which may affect the biological functions of MAD2L1.

Conclusion: This study indicated that Neratinib could interact with MAD2L1 and lead to the conformational change of MAD2L1. These works provide helpful insights for the further study of biological function of MAD2L1 and novel pharmacological utility of Neratinib.

Keywords: MAD2L1, Neratinib, Interaction, Multi-spectroscopy, molecular docking, Quenching.

Kato T, Daigo Y, Aragaki M, et al. Overexpression of MAD2 predicts clinical outcome in primary lung cancer patients. Lung Cancer 2011; 74(1): 124-31.
[] [PMID: 21376419]
Pino MS, Chung DC. The chromosomal instability pathway in colon cancer. Gastroenterology 2010; 138(6): 2059-72.
[] [PMID: 20420946]
Musacchio A, Salmon ED. The spindle-assembly checkpoint in space and time. Nat Rev Mol Cell Biol 2007; 8(5): 379-93.
[] [PMID: 17426725]
Gay S. A novel function for the mitotic checkpoint protein Mad2p in translation. Mol Cell Oncol 2018; 5(4) e1494949
[] [PMID: 30250931]
Furlong F, Fitzpatrick P, O’Toole S, et al. Low MAD2 expression levels associate with reduced progression-free survival in patients with high-grade serous epithelial ovarian cancer. J Pathol 2012; 226(5): 746-55.
[] [PMID: 22069160]
Zhong R, Chen X, Chen X, et al. MAD1L1 Arg558His and MAD2L1 Leu84Met interaction with smoking increase the risk of colorectal cancer. Sci Rep 2015; 5: 12202.
[] [PMID: 26183163]
Li Y, Bai W, Zhang J. MiR-200c-5p suppresses proliferation and metastasis of human hepatocellular carcinoma (HCC) via suppressing MAD2L1. Biomed Pharmacother 2017; 92: 1038-44.
[] [PMID: 28609841]
Chen RH, Shevchenko A, Mann M, Murray AW. Spindle checkpoint protein Xmad1 recruits Xmad2 to unattached kinetochores. J Cell Biol 1998; 143(2): 283-95.
[] [PMID: 9786942]
Chen RH, Brady DM, Smith D, Murray AW, Hardwick KG. The spindle checkpoint of budding yeast depends on a tight complex between the Mad1 and Mad2 proteins. Mol Biol Cell 1999; 10(8): 2607-18.
[] [PMID: 10436016]
De Antoni A, Pearson CG, Cimini D, et al. The Mad1/Mad2 complex as a template for Mad2 activation in the spindle assembly checkpoint. Curr Biol 2005; 15(3): 214-25.
[] [PMID: 15694304]
Luo X, Fang G, Coldiron M, et al. Structure of the Mad2 spindle assembly checkpoint protein and its interaction with Cdc20. Nat Struct Biol 2000; 7(3): 224-9.
[] [PMID: 10700282]
Fang G, Yu H, Kirschner MW. The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary complex with the anaphase-promoting complex to control anaphase initiation. Genes Dev 1998; 12(12): 1871-83.
[] [PMID: 9637688]
Zhu XF, Yi M, He J, et al. Pathological significance of MAD2L1 in breast cancer: an immunohistochemical study and meta analysis. Int J Clin Exp Pathol 2017; 10(9): 9190-201.
Michel LS, Liberal V, Chatterjee A, et al. MAD2 haplo-insufficiency causes premature anaphase and chromosome instability in mammalian cells. Nature 2001; 409(6818): 355-9.
[] [PMID: 11201745]
Sotillo R, Hernando E, Díaz-Rodríguez E, et al. Mad2 overexpression promotes aneuploidy and tumorigenesis in mice. Cancer Cell 2007; 11(1): 9-23.
[] [PMID: 17189715]
Shi YX, Zhu T, Zou T, et al. Prognostic and predictive values of CDK1 and MAD2L1 in lung adenocarcinoma. Oncotarget 2016; 7(51): 85235-43.
[] [PMID: 27835911]
Zhou W, Yin M, Cui H, et al. Identification of potential therapeutic target genes and mechanisms in non-small-cell lung carcinoma in non-smoking women based on bioinformatics analysis. Eur Rev Med Pharmacol Sci 2015; 19(18): 3375-84.
[PMID: 26439031]
Wang Z, Katsaros D, Shen Y, et al. Biological and clinical significance of MAD2L1 and BUB1, genes frequently appearing in expression signatures for breast cancer prognosis. PLoS One 2015; 10(8)e0136246
[] [PMID: 26287798]
Percy MJ, Myrie KA, Neeley CK, Azim JN, Ethier SP, Petty EM. Expression and mutational analyses of the human MAD2L1 gene in breast cancer cells. Genes Chromosomes Cancer 2000; 29(4): 356-62.
[<:AID-GCC1044>3.0.CO;2-N] [PMID: 11066082]
Zhang SH, Xu AM, Chen XF, Li DH, Sun MP, Wang YJ. Clinicopathologic significance of mitotic arrest defective protein 2 overexpression in hepatocellular carcinoma. Hum Pathol 2008; 39(12): 1827-34.
[] [PMID: 18715617]
Chen X, Cheung ST, So S, et al. Gene expression patterns in human liver cancers. Mol Biol Cell 2002; 13(6): 1929-39.
[] [PMID: 12058060]
Menyhart O, Nagy A, Gyorffy B. Determining consistentprognostic biomarkers of overall survival and vascular invasion in hepatocellular carcinoma. R Soc Open Sci 5 181006
[] [PMID: 30662724 ]
Bargiela-Iparraguirre J, Prado-Marchal L, Pajuelo-Lozano N, Jiménez B, Perona R, Sánchez-Pérez I. Mad2 and BubR1 modulates tumourigenesis and paclitaxel response in MKN45 gastric cancer cells. Cell Cycle 2014; 13(22): 3590-601.
[] [PMID: 25483095]
Kiesel BF, Parise RA, Wong A, Keyvanjah K, Jacobs S, Beumer JH. LC-MS/MS assay for the quantitation of the tyrosine kinase inhibitor neratinib in human plasma. J Pharm Biomed Anal 2017; 134: 130-6.
[] [PMID: 27907855]
Wani TA, Bakheit AH, Abounassif MA, Zargar S. Study of interactions of an anticancer drug neratinib with bovine serum albumin: spectroscopic and molecular docking approach. Front Chem 2018; 6: 47.
[] [PMID: 29564326]
Rabindran SK, Discafani CM, Rosfjord EC, et al. Antitumor activity of HKI-272, an orally active, irreversible inhibitor of the HER-2 tyrosine kinase. Cancer Res 2004; 64(11): 3958-65.
[] [PMID: 15173008]
Seyhan AA, Varadarajan U, Choe S, Liu W, Ryan TE. A genome-wide RNAi screen identifies novel targets of neratinib resistance leading to identification of potential drug resistant genetic markers. Mol Biosyst 2012; 8(5): 1553-70.
[] [PMID: 22446932]
Blackwell KL, Zaman K, Qin S, et al. 202 Study group. neratinib in combination with trastuzumab for the treatment of patients with advanced HER2-positive breast cancer: a phase I/II study. Clin Breast Cancer 2019; 19(2): 97-104. e4
[] [PMID: 30655172]
Zhang Y, Zhang J, Liu C, et al. Neratinib induces ErbB2 ubiquitylation and endocytic degradation via HSP90 dissociation in breast cancer cells. Cancer Lett 2016; 382(2): 176-85.
[] [PMID: 27597738]
Schwab CL, English DP, Roque DM, et al. Neratinib shows efficacy in the treatment of HER2/neu amplified uterine serous carcinoma in vitro and in vivo. Gynecol Oncol 2014; 135(1): 142-8.
[] [PMID: 25124161]
Schwab CL, English DP, Black J, et al. Neratinib shows efficacy in the treatment of HER2 amplified carcinosarcoma in vitro and in vivo. Gynecol Oncol 2015; 139(1): 112-7.
[] [PMID: 26260909]
Ogoshi Y. P3.13-35 antitumor effect of neratinib targeting HER2-altered lung cancer. J Thorac Oncol 2018; 13(10)(Suppl.): S990.
Sequist LV, Besse B, Lynch TJ, et al. Neratinib, an irreversible pan-ErbB receptor tyrosine kinase inhibitor: results of a phase II trial in patients with advanced non-small-cell lung cancer. J Clin Oncol 2010; 28(18): 3076-83.
[] [PMID: 20479403]
Gandhi L, Besse B, Mazieres J, et al. MA04.02 neratinib ± temsirolimus in HER2-mutant lung cancers: an international, randomized phase II study. J Thorac Oncol 2017; 12(1)(Suppl.): S358-9.
Booth L, Roberts JL, Poklepovic A, et al. HDAC inhibitors enhance neratinib activity and when combined enhance the actions of an anti-PD-1 immunomodulatory antibody in vivo. Oncotarget 2017; 8(52): 90262-77.
[] [PMID: 29163826]
Sallum LO, Vaz WF, Borges NM, et al. Synthesis, conformational analysis and molecular docking studies on three novel dihydropyrimidine derivatives. J Mol Struct 2019; 1192: 274-87.
Zaman K, Rahim F, Taha M, et al. Synthesis, thymidine phosphorylase, angiogenic inhibition and molecular docking study of isoquinoline derivatives. Bioorg Chem 2019; 89 102999
[] [PMID: 31151055]
Sun Q, Yang H, Tang P, Liu J, Wang W, Li H. Interactions of cinnamaldehyde and its metabolite cinnamic acid with human serum albumin and interference of other food additives. Food Chem 2018; 243: 74-81.
[] [PMID: 29146372]
Nan Z, Hao C, Ye X, Feng Y, Sun R. Interaction of graphene oxide with bovine serum albumin: a fluorescence quenching study. Spectrochim Acta A Mol Biomol Spectrosc 2019; 210: 348-54.
[] [PMID: 30476875]
Zhang Y-F, Zhou K-L, Lou Y-Y, Pan DQ, Shi J-H. Investigation of the binding interaction between estazolam and bovine serum albumin: multi-spectroscopic methods and molecular docking technique. J Biomol Struct Dyn 2017; 35(16): 3605-14.
[] [PMID: 27882826]
Gelamo EL, Silva CH, Imasato H, Tabak M. Interaction of bovine (BSA) and human (HSA) serum albumins with ionic surfactants: spectroscopy and modelling. Biochim Biophys Acta 2002; 1594(1): 84-99.
[] [PMID: 11825611]
Lakowicz JR, Weber G. Quenching of fluorescence by oxygen. A probe for structural fluctuations in macromolecules. Biochemistry 1973; 12(21): 4161-70.
[] [PMID: 4795686]
Hao C, Xu G, Feng Y, Lu L, Sun W, Sun R. Fluorescence quenching study on the interaction of ferroferric oxide nanoparticles with bovine serum albumin. Spectrochim Acta A Mol Biomol Spectrosc 2017; 184: 191-7.
[] [PMID: 28499172]
Zhou Q, Xiang J, Tang Y, et al. Investigation on the interaction between a heterocyclic aminal derivative, SBDC, and human serum albumin. Colloids Surf B Biointerfaces 2008; 61(1): 75-80.
[] [PMID: 17768036]
Gerbanowski A, Malabat C, Rabiller C, Guéguen J. Grafting of aliphatic and aromatic probes on rapeseed 2S and 12S proteins: influence on their structural and physicochemical properties. J Agric Food Chem 1999; 47(12): 5218-26.
[] [PMID: 10606599]
Naik DB, Moorthy PN, Priyadarsini KI. Nonradiative energy transfer from 7-amino coumarin dyes to thiazine dyes in methanolic solutions. Chem Phys Lett 1990; 168(6): 533-8.
Horrocks WD, Collier WE. Lanthanide ion luminescence probes. Measurement of distance between intrinsic protein fluorophores and bound metal ions: quantitation of energy transfer between tryptophan and terbium(III) or europium(III) in the calcium-binding protein parvalbumin. J Am Chem Soc 1981; 103(10): 2856-62.
Sklar LA, Hudson BS, Simoni RD. Conjugated polyene fatty acids as fluorescent probes: synthetic phospholipid membrane studies. Biochemistry 1977; 16(5): 819-28.
[] [PMID: 843518]
Wu P, Brand L. Resonance energy transfer: methods and applications. Anal Biochem 1994; 218(1): 1-13.
[] [PMID: 8053542]
Förster T. Delocalized Excitation and Excitation Transfer 1965.
Li DJ, Zhu JF, Jin J, Yao XJ. Studies on the binding of nevadensin to human serum albumin by molecular spectroscopy and modeling. J Mol Struct 2007; 846(1-3): 34-41.
Hu YJ, Liu Y, Hou AX, Zhao RM, Qu XS, Qu SS. Studies on the interaction between rare-earth salts of heteropoly EuHSiMoW2O40 center dot 25H(2)O and bovine serum albumin. Acta Chimi Sin 2004; 62(16): 1519-23.
Zhang YZ, Zhou B, Liu YX, Zhou CX, Ding XL, Liu Y. Fluorescence study on the interaction of bovine serum albumin with p-aminoazobenzene. J Fluoresc 2008; 18(1): 109-18.
[] [PMID: 17899332]
Cacita N, Nikolaou S. Studying the interaction between trinuclear ruthenium complexes and human serum albumin by means of fluorescence quenching. J Lumin 2016; 169: 115-20.
Ross PD, Subramanian S. Thermodynamics of protein association reactions: forces contributing to stability. Biochemistry 1981; 20(11): 3096-102.
[] [PMID: 7248271]
Sun Q, Gao X, Bi H, Xie Y, Tang L. Assessment of binding interaction between bovine lactoferrin and tetracycline hydrochloride: multi-spectroscopic analyses and molecular modeling. Molecules 2018; 23(8): 17.
[] [PMID: 30061508]
Byadagi K, Meti M, Nandibewoor S, Chimatadar S. Investigation of binding behaviour of procainamide hydrochloride with human serum albumin using synchronous, 3D fluorescence and circular dichroism. J Pharm Anal 2017; 7(2): 103-9.
[] [PMID: 29404024]
Yuan T, Weljie AM, Vogel HJ. Tryptophan fluorescence quenching by methionine and selenomethionine residues of calmodulin: orientation of peptide and protein binding. Biochemistry 1998; 37(9): 3187-95.
[] [PMID: 9485473]
Wang YQ, Zhang HM, Zhang GC, et al. Fluorescence spectroscopic investigation of the interaction between benzidine and bovine hemoglobin. J Mol Struct 2008; 886(1-3): 77-84.
Patil SR, Salunkhe SM, Wakshe SB, et al. Spectral elucidation with molecular docking study between isatin analogous and bovine serum albumin. Chemical Data Collections 2019; 22 100254
Zhang G, Que Q, Pan J, Guo J. Study of the interaction between icariin and human serum albumin by fluorescence spectroscopy. J Mol Struct 2008; 881(1): 132-8.
Bagoji AM, Buddanavar AT, Gokavi NM, Nandibewoor ST. Characterization of the binding and conformational changes of bovine serum albumin upon interaction with antihypertensive olmesartan medoxomil. J Mol Struct 2019; 1179: 269-77.
Wang YR, Fang W, Guo CH, Liu Y. Probing the binding of torasemide to pepsin and trypsin by spectroscopic and molecular docking methods. Guang Pu Xue Yu Guang Pu Fen Xi 2016; 36(10): 3414-21.
[PMID: 30247002]
Ren G, Sun H, Li G, Fan J, Wu Y, Cui G. Molecular docking and muiltple spectroscopy investigation on the binding characteristics of aloe-emodin to pepsin. J Mol Struct 2019; 1195: 369-77.
Koshland D E. The key-lock theory and the induced fit theory 1995.
Raajaraman BR, Sheela NR, Muthu S. Spectroscopic, quantum computational and molecular docking studies on 1-phenylcyclo-pentane carboxylic acid. Comput Biol Chem 2019; 82: 44-56.
[] [PMID: 31260880]
Papadopoulou A, Green RJ, Frazier RA. Interaction of flavonoids with bovine serum albumin: a fluorescence quenching study. J Agric Food Chem 2005; 53(1): 158-63.
[] [PMID: 15631523]
Xiao J, Wei X, Wang Y, Liu C. Fluorescence resonance energy-transfer affects the determination of the affinity between ligand and proteins obtained by fluorescence quenching method. Spectrochim Acta A Mol Biomol Spectrosc 2009; 74(4): 977-82.
[] [PMID: 19783471]
Shi J-h, Wang J, Zhu Y-y, Chen J. Characterization of interaction between isoliquiritigenin and bovine serum albumin: spectroscopic and molecular docking methods. J Lumin 2014; 145: 643-50.
Wani TA, AlRabiah H, Bakheit AH, Kalam MA, Zargar S. Study of binding interaction of rivaroxaban with bovine serum albumin using multi-spectroscopic and molecular docking approach. Chem Cent J 2017; 11(1): 134-4.
[] [PMID: 29260434]
Ni Y, Liu G, Kokot S. Fluorescence spectrometric study on the interactions of Isoprocarb and sodium 2-isopropylphenate with bovine serum albumin. Talanta 2008; 76(3): 513-21.
[] [PMID: 18585315]

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