Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Review Article

The Potential Strategies for Overcoming Multidrug Resistance and Reducing Side Effects of Monomer Tubulin Inhibitors for Cancer Therapy

Author(s): Yingjie Cui*, Jing Zhang and Guifang Zhang

Volume 31, Issue 14, 2024

Published on: 29 August, 2023

Page: [1874 - 1895] Pages: 22

DOI: 10.2174/0929867330666230622142505

Price: $65

Open Access Journals Promotions 2
Abstract

Background: Tubulin is an essential target in tumor therapy, and this is attributed to its ability to target MT dynamics and interfere with critical cellular functions, including mitosis, cell signaling, and intracellular trafficking. Several tubulin inhibitors have been approved for clinical application. However, the shortcomings, such as drug resistance and toxic side effects, limit its clinical application. Compared with single-target drugs, multi-target drugs can effectively improve efficacy to reduce side effects and overcome the development of drug resistance. Tubulin protein degraders do not require high concentrations and can be recycled. After degradation, the protein needs to be resynthesized to regain function, which significantly delays the development of drug resistance.

Methods: Using SciFinder® as a tool, the publications about tubulin-based dual-target inhibitors and tubulin degraders were surveyed with an exclusion of those published as patents.

Results: This study presents the research progress of tubulin-based dual-target inhibitors and tubulin degraders as antitumor agents to provide a reference for developing and applying more efficient drugs for cancer therapy.

Conclusion: The multi-target inhibitors and protein degraders have shown a development prospect to overcome multidrug resistance and reduce side effects in the treatment of tumors. Currently, the design of dual-target inhibitors for tubulin needs to be further optimized, and it is worth further clarifying the detailed mechanism of protein degradation.

Keywords: Tubulin inhibitors, tubulin-based dual-target inhibitors, protein degraders, multidrug resistance, side effects, cancer therapy.

« Previous Next »
[1]
Sambrani, R.; Abdolalizadeh, J.; Kohan, L.; Jafari, B. Recent advances in the application of probiotic yeasts, particularly Saccharomyces, as an adjuvant therapy in the management of cancer with focus on colorectal cancer. Mol. Biol. Rep., 2021, 48(1), 951-960.
[http://dx.doi.org/10.1007/s11033-020-06110-1] [PMID: 33389533]
[2]
Ferlay, J.; Colombet, M.; Soerjomataram, I.; Mathers, C.; Parkin, D.M.; Piñeros, M.; Znaor, A.; Bray, F. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int. J. Cancer, 2019, 144(8), 1941-1953.
[http://dx.doi.org/10.1002/ijc.31937] [PMID: 30350310]
[3]
Kovács, D. Szőke, K.; Igaz, N.; Spengler, G.; Molnár, J.; Tóth, T.; Madarász, D.; Rázga, Z.; Kónya, Z.; Boros, I.M.; Kiricsi, M. Silver nanoparticles modulate ABC transporter activity and enhance chemotherapy in multidrug resistant cancer. Nanomedicine, 2016, 12(3), 601-610.
[http://dx.doi.org/10.1016/j.nano.2015.10.015] [PMID: 26656631]
[4]
Cui, Y.J.; Liu, C.; Ma, C.C.; Ji, Y.T.; Yao, Y.L.; Tang, L.Q.; Zhang, C.M.; Wu, J.D.; Liu, Z.P. SAR investigation and discovery of water-soluble 1-methyl-1,4-dihydroindeno[1,2-c]pyrazoles as potent tubulin polymerization inhibitors. J. Med. Chem., 2020, 63(23), 14840-14866.
[http://dx.doi.org/10.1021/acs.jmedchem.0c01345] [PMID: 33201714]
[5]
Feng, Z.Q.; Yan, K.; Li, J.; Xu, X.; Yuan, T.; Wang, T.; Zheng, J. Magnetic Janus particles as a multifunctional drug delivery system for paclitaxel in efficient cancer treatment. Mater. Sci. Eng. C, 2019, 104, 110001.
[http://dx.doi.org/10.1016/j.msec.2019.110001] [PMID: 31500023]
[6]
García-Galindo, G.; Castro, J.; Matés, J.; Bravo, M.; Ribó, M.; Vilanova, M.; Benito, A. The selectivity for tumor cells of nuclear-directed cytotoxic RNases is mediated by the nuclear/cytoplasmic distribution of p27(KIP1). Molecules, 2021, 26(5), 1319.
[http://dx.doi.org/10.3390/molecules26051319] [PMID: 33801209]
[7]
Ashaq, A.; Maqbool, M.F.; Maryam, A.; Khan, M.; Shakir, H.A.; Irfan, M.; Qazi, J.I.; Li, Y.; Ma, T. Hispidulin: A novel natural compound with therapeutic potential against human cancers. Phytother. Res., 2021, 35(2), 771-789.
[http://dx.doi.org/10.1002/ptr.6862] [PMID: 32945582]
[8]
Rawat, R.; Verma, S.M. High-throughput virtual screening approach involving pharmacophore mapping, ADME filtering, molecular docking and MM-GBSA to identify new dual target inhibitors of Pf DHODH and Pf Cytbc1 complex to combat drug resistant malaria. J. Biomol. Struct. Dyn., 2021, 39(14), 5148-5159.
[http://dx.doi.org/10.1080/07391102.2020.1784288] [PMID: 32579074]
[9]
Raghavendra, N.M.; Pingili, D.; Kadasi, S.; Mettu, A.; Prasad, S.V.U.M. Dual or multi-targeting inhibitors: The next generation anticancer agents. Eur. J. Med. Chem., 2018, 143, 1277-1300.
[http://dx.doi.org/10.1016/j.ejmech.2017.10.021] [PMID: 29126724]
[10]
Zhang, X.; Zegar, T.; Weiser, T.; Hamdan, F.H.; Berger, B.T.; Lucas, R.; Balourdas, D.I.I.; Ladigan, S.; Cheung, P.F.; Liffers, S.T.; Trajkovic-Arsic, M.; Scheffler, B.; Joerger, A.C.; Hahn, S.A.; Johnsen, S.A.; Knapp, S.; Siveke, J.T. Characterization of a dual BET/HDAC inhibitor for treatment of pancreatic ductal adenocarcinoma. Int. J. Cancer, 2020, 147(10), 2847-2861.
[http://dx.doi.org/10.1002/ijc.33137] [PMID: 32599645]
[11]
Ren, Q.; Gao, W. Current status in the discovery of dual BET/HDAC inhibitors. Bioorg. Med. Chem. Lett., 2021, 38, 127829.
[http://dx.doi.org/10.1016/j.bmcl.2021.127829] [PMID: 33685790]
[12]
Skok, Ž.; Zidar, N.; Kikelj, D.; Ilaš, J. Dual inhibitors of human DNA topoisomerase II and other cancer-related targets. J. Med. Chem., 2020, 63(3), 884-904.
[http://dx.doi.org/10.1021/acs.jmedchem.9b00726] [PMID: 31592646]
[13]
Werth, E.G.; Rajbhandari, P.; Stockwell, B.R.; Brown, L.M. Time course of changes in sorafenib-treated hepatocellular carcinoma cells suggests involvement of phospho-regulated signaling in ferroptosis induction. Proteomics, 2020, 20(10), 2000006.
[http://dx.doi.org/10.1002/pmic.202000006] [PMID: 32336023]
[14]
Du, G.; Rao, S.; Gurbani, D.; Henning, N.J.; Jiang, J.; Che, J.; Yang, A.; Ficarro, S.B.; Marto, J.A.; Aguirre, A.J.; Sorger, P.K.; Westover, K.D.; Zhang, T.; Gray, N.S. Structure-based design of a potent and selective covalent inhibitor for SRC kinase that targets a p-loop cysteine. J. Med. Chem., 2020, 63(4), 1624-1641.
[http://dx.doi.org/10.1021/acs.jmedchem.9b01502] [PMID: 31935084]
[15]
Conlon, N.T.; Kooijman, J.J.; van Gerwen, S.J.C.; Mulder, W.R.; Zaman, G.J.R.; Diala, I.; Eli, L.D.; Lalani, A.S.; Crown, J.; Collins, D.M. Comparative analysis of drug response and gene profiling of HER2-targeted tyrosine kinase inhibitors. Br. J. Cancer, 2021, 124(7), 1249-1259.
[http://dx.doi.org/10.1038/s41416-020-01257-x] [PMID: 33473169]
[16]
Yang, J.; Li, Y.; Qiu, Q.; Wang, R.; Yan, W.; Yu, Y.; Niu, L.; Pei, H.; Wei, H.; Ouyang, L.; Ye, H.; Xu, D.; Wei, Y.; Chen, Q.; Chen, L. Small molecules promote selective denaturation and degradation of tubulin heterodimers through a low-barrier hydrogen bond. J. Med. Chem., 2022, 65(13), 9159-9173.
[http://dx.doi.org/10.1021/acs.jmedchem.2c00379] [PMID: 35762925]
[17]
Schummel, P.H.; Gao, M.; Winter, R. Modulation of the polymerization kinetics of α/β-tubulin by osmolytes and macromolecular crowding. ChemPhysChem, 2017, 18(2), 189-197.
[http://dx.doi.org/10.1002/cphc.201601032] [PMID: 27813294]
[18]
Cantero, M.R.; Perez, P.L.; Scarinci, N.; Cantiello, H.F. Two-dimensional brain microtubule structures behave as memristive devices. Sci. Rep., 2019, 9(1), 12398.
[http://dx.doi.org/10.1038/s41598-019-48677-1] [PMID: 31455820]
[19]
Janke, C. The tubulin code: Molecular components, readout mechanisms, and functions. J. Cell Biol., 2014, 206(4), 461-472.
[http://dx.doi.org/10.1083/jcb.201406055] [PMID: 25135932]
[20]
Liang, Y.J.; Yang, W.X. Kinesins in MAPK cascade: How kinesin motors are involved in the MAPK pathway? Gene, 2019, 684, 1-9.
[http://dx.doi.org/10.1016/j.gene.2018.10.042] [PMID: 30342167]
[21]
Kalous, J.; Tetkova, A.; Kubelka, M.; Susor, A. Importance of ERK1/2 in regulation of protein translation during oocyte meiosis. Int. J. Mol. Sci., 2018, 19(3), 698.
[http://dx.doi.org/10.3390/ijms19030698] [PMID: 29494492]
[22]
Laflamme, G.; Sim, S.; Leary, A.; Pascariu, M.; Vogel, J.; D’Amours, D. Interphase microtubules safeguard mitotic progression by suppressing an Aurora B-dependent arrest induced by DNA replication stress. Cell Rep., 2019, 26(11), 2875-2889.e3.
[http://dx.doi.org/10.1016/j.celrep.2019.02.051] [PMID: 30865880]
[23]
Steinmetz, M.O.; Prota, A.E. Microtubule-targeting agents: Strategies to hijack the cytoskeleton. Trends Cell Biol., 2018, 28(10), 776-792.
[http://dx.doi.org/10.1016/j.tcb.2018.05.001] [PMID: 29871823]
[24]
Bennett, M.J.; Barakat, K.; Huzil, J.T.; Tuszynski, J.; Schriemer, D.C. Discovery and characterization of the laulimalide-microtubule binding mode by mass shift perturbation mapping. Chem. Biol., 2010, 17(7), 725-734.
[http://dx.doi.org/10.1016/j.chembiol.2010.05.019] [PMID: 20659685]
[25]
Shuai, W.; Li, X.; Li, W.; Xu, F.; Lu, L.; Yao, H.; Yang, L.; Zhu, H.; Xu, S.; Zhu, Z.; Xu, J. Design, synthesis and anticancer properties of isocombretapyridines as potent colchicine binding site inhibitors. Eur. J. Med. Chem., 2020, 197, 112308.
[http://dx.doi.org/10.1016/j.ejmech.2020.112308] [PMID: 32339853]
[26]
Lobert, S.; Correia, J.J. Energetics of vinca alkaloid interactions with tubulin. Methods Enzymol., 2000, 323, 77-103.
[http://dx.doi.org/10.1016/S0076-6879(00)23362-4] [PMID: 10944748]
[27]
Prota, A.E.; Bargsten, K.; Diaz, J.F.; Marsh, M.; Cuevas, C.; Liniger, M.; Neuhaus, C.; Andreu, J.M.; Altmann, K.H.; Steinmetz, M.O. A new tubulin-binding site and pharmacophore for microtubule-destabilizing anticancer drugs. Proc. Natl. Acad. Sci. USA, 2014, 111(38), 13817-13821.
[http://dx.doi.org/10.1073/pnas.1408124111] [PMID: 25114240]
[28]
Prota, A.E.; Setter, J.; Waight, A.B.; Bargsten, K.; Murga, J.; Diaz, J.F.; Steinmetz, M.O. Pironetin binds covalently to αCys316 and perturbs a major loop and helix of α-tubulin to inhibit microtubule formation. J. Mol. Biol., 2016, 428(15), 2981-2988.
[http://dx.doi.org/10.1016/j.jmb.2016.06.023] [PMID: 27395016]
[29]
Canta, A.; Chiorazzi, A.; Cavaletti, G. Tubulin: a target for antineoplastic drugs into the cancer cells but also in the peripheral nervous system. Curr. Med. Chem., 2009, 16(11), 1315-1324.
[http://dx.doi.org/10.2174/092986709787846488] [PMID: 19355888]
[30]
Komatsu, M.; Wheeler, H.E.; Chung, S.; Low, S.K.; Wing, C.; Delaney, S.M.; Gorsic, L.K.; Takahashi, A.; Kubo, M.; Kroetz, D.L.; Zhang, W.; Nakamura, Y.; Dolan, M.E. Pharmacoethnicity in paclitaxel-induced sensory peripheral neuropathy. Clin. Cancer Res., 2015, 21(19), 4337-4346.
[http://dx.doi.org/10.1158/1078-0432.CCR-15-0133] [PMID: 26015512]
[31]
Eckford, P.D.W.; Sharom, F.J. ABC efflux pump-based resistance to chemotherapy drugs. Chem. Rev., 2009, 109(7), 2989-3011.
[http://dx.doi.org/10.1021/cr9000226] [PMID: 19583429]
[32]
Verma, S.; Miles, D.; Gianni, L.; Krop, I.E.; Welslau, M.; Baselga, J.; Pegram, M.; Oh, D.Y.; Diéras, V.; Guardino, E.; Fang, L.; Lu, M.W.; Olsen, S.; Blackwell, K. Trastuzumab emtansine for HER2-positive advanced breast cancer. N. Engl. J. Med., 2012, 367(19), 1783-1791.
[http://dx.doi.org/10.1056/NEJMoa1209124] [PMID: 23020162]
[33]
Schmitt, F.; Gosch, L.; Dittmer, A.; Rothemund, M.; Mueller, T.; Schobert, R.; Biersack, B.; Volkamer, A.; Höpfner, M. Oxazole-bridged combretastatin A-4 derivatives with tethered hydroxamic acids: Structure(-)activity relations of new inhibitors of HDAC and/or tubulin function. Int. J. Mol. Sci., 2019, 20(2), 383.
[http://dx.doi.org/10.3390/ijms20020383] [PMID: 30658435]
[34]
Wang, B.; Chen, X.; Gao, J.; Su, L.; Zhang, L.; Xu, H.; Luan, Y. Anti-tumor activity evaluation of novel tubulin and HDAC dual-targeting inhibitors. Bioorg. Med. Chem. Lett., 2019, 29(18), 2638-2645.
[http://dx.doi.org/10.1016/j.bmcl.2019.07.045] [PMID: 31400938]
[35]
Zhang, X.; Zhang, J.; Tong, L.; Luo, Y.; Su, M.; Zang, Y.; Li, J.; Lu, W.; Chen, Y. The discovery of colchicine-SAHA hybrids as a new class of antitumor agents. Bioorg. Med. Chem., 2013, 21(11), 3240-3244.
[http://dx.doi.org/10.1016/j.bmc.2013.03.049] [PMID: 23602523]
[36]
Thaler, F. Current trends in the development of histone deacetylase inhibitors: a review of recent patent applications. Pharm. Pat. Anal., 2012, 1(1), 75-90.
[http://dx.doi.org/10.4155/ppa.11.3] [PMID: 24236715]
[37]
Zhang, X.; Kong, Y.; Zhang, J.; Su, M.; Zhou, Y.; Zang, Y.; Li, J.; Chen, Y.; Fang, Y.; Zhang, X.; Lu, W. Design, synthesis and biological evaluation of colchicine derivatives as novel tubulin and histone deacetylase dual inhibitors. Eur. J. Med. Chem., 2015, 95, 127-135.
[http://dx.doi.org/10.1016/j.ejmech.2015.03.035] [PMID: 25805446]
[38]
Lee, H.Y.; Lee, J.F.; Kumar, S.; Wu, Y.W. HuangFu, W.C.; Lai, M.J.; Li, Y.H.; Huang, H.L.; Kuo, F.C.; Hsiao, C.J.; Cheng, C.C.; Yang, C.R.; Liou, J.P. 3-Aroylindoles display antitumor activity in vitro and in vivo: Effects of N1-substituents on biological activity. Eur. J. Med. Chem., 2017, 125, 1268-1278.
[http://dx.doi.org/10.1016/j.ejmech.2016.11.033] [PMID: 27886544]
[39]
Wu, Y.W.; Hsu, K.C.; Lee, H.Y.; Huang, T.C.; Lin, T.E.; Chen, Y.L.; Sung, T.Y.; Liou, J.P.; Hwang-Verslues, W.W.; Pan, S.L. HuangFu, W.C. HuangFu, W.C. A novel dual HDAC6 and tubulin inhibitor, MPT0B451, displays anti-tumor ability in human cancer cells in vitro and in vivo. Front. Pharmacol., 2018, 9, 205.
[http://dx.doi.org/10.3389/fphar.2018.00205] [PMID: 29593536]
[40]
Lamaa, D.; Lin, H.P.; Zig, L.; Bauvais, C.; Bollot, G.; Bignon, J.; Levaique, H.; Pamlard, O.; Dubois, J.; Ouaissi, M.; Souce, M.; Kasselouri, A.; Saller, F.; Borgel, D.; Jayat-Vignoles, C.; Al-Mouhammad, H.; Feuillard, J.; Benihoud, K.; Alami, M.; Hamze, A. Design and synthesis of tubulin and histone deacetylase inhibitor based on iso-combretastatin A-4. J. Med. Chem., 2018, 61(15), 6574-6591.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00050] [PMID: 30004697]
[41]
Aboeldahab, A.M.A.; Beshr, E.A.M.; Shoman, M.E.; Rabea, S.M.; Aly, O.M. Spirohydantoins and 1,2,4-triazole-3-carboxamide derivatives as inhibitors of histone deacetylase: Design, synthesis, and biological evaluation. Eur. J. Med. Chem., 2018, 146, 79-92.
[http://dx.doi.org/10.1016/j.ejmech.2018.01.021] [PMID: 29396364]
[42]
Mourad, A.A.E.; Mourad, M.A.E.; Jones, P.G. Novel HDAC/tubulin dual inhibitor: Design, synthesis and docking studies of alpha-phthalimido-chalcone hybrids as potential anticancer agents with apoptosis-inducing activity. Drug Des. Devel. Ther., 2020, 14, 3111-3130.
[http://dx.doi.org/10.2147/DDDT.S256756] [PMID: 32848361]
[43]
Lai, M.J.; Ojha, R.; Lin, M.H.; Liu, Y.M.; Lee, H.Y.; Lin, T.E.; Hsu, K.C.; Chang, C.Y.; Chen, M.C.; Nepali, K.; Chang, J.Y.; Liou, J.P. 1-arylsulfonyl indoline-benzamides as a new antitubulin agents, with inhibition of histone deacetylase. Eur. J. Med. Chem., 2019, 162, 612-630.
[http://dx.doi.org/10.1016/j.ejmech.2018.10.066] [PMID: 30476825]
[44]
Talukdar, S.; Emdad, L.; Das, S.K.; Fisher, P.B. EGFR: An essential receptor tyrosine kinase-regulator of cancer stem cells. Adv. Cancer Res., 2020, 147, 161-188.
[http://dx.doi.org/10.1016/bs.acr.2020.04.003] [PMID: 32593400]
[45]
Sun, W.X.; Han, H.W.; Yang, M.K.; Wen, Z.L.; Wang, Y.S.; Fu, J.Y.; Lu, Y.T.; Wang, M.Y.; Bao, J.X.; Lu, G.H.; Qi, J.L.; Wang, X.M.; Lin, H.Y.; Yang, Y.H. Design, synthesis and biological evaluation of benzoylacrylic acid shikonin ester derivatives as irreversible dual inhibitors of tubulin and EGFR. Bioorg. Med. Chem., 2019, 27(23), 115153.
[http://dx.doi.org/10.1016/j.bmc.2019.115153] [PMID: 31648877]
[46]
Aouad, M.R.; Al-Mohammadi, H.M.; Al-blewi, F.F.; Ihmaid, S.; Elbadawy, H.M.; Althagfan, S.S.; Rezki, N. Introducing of acyclonucleoside analogues tethered 1,2,4-triazole as anticancer agents with dual epidermal growth factor receptor kinase and microtubule inhibitors. Bioorg. Chem., 2020, 94, 103446.
[http://dx.doi.org/10.1016/j.bioorg.2019.103446] [PMID: 31791685]
[47]
Romagnoli, R.; Prencipe, F.; Oliva, P.; Baraldi, S.; Baraldi, P.G.; Schiaffino Ortega, S.; Chayah, M.; Kimatrai Salvador, M.; Lopez-Cara, L.C.; Brancale, A.; Ferla, S.; Hamel, E.; Ronca, R.; Bortolozzi, R.; Mariotto, E.; Mattiuzzo, E.; Viola, G. Design, synthesis, and biological evaluation of 6-substituted thieno[3,2-d]pyrimidine analogues as dual epidermal growth factor receptor kinase and microtubule inhibitors. J. Med. Chem., 2019, 62(3), 1274-1290.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01391] [PMID: 30633509]
[48]
Alswah, M.; Bayoumi, A.; Elgamal, K.; Elmorsy, A.; Ihmaid, S.; Ahmed, H. Design, synthesis and cytotoxic evaluation of novel chalcone derivatives bearing triazolo[4,3-a]-quinoxaline moieties as potent anticancer agents with dual EGFR kinase and tubulin polymerization inhibitory effects. Molecules, 2017, 23(1), 48.
[http://dx.doi.org/10.3390/molecules23010048] [PMID: 29280968]
[49]
Zayed, M.; Rateb, H.; Ahmed, S.; Khaled, O.; Ibrahim, S. Quinazolinone-amino acid hybrids as dual inhibitors of EGFR kinase and tubulin polymerization. Molecules, 2018, 23(7), 1699.
[http://dx.doi.org/10.3390/molecules23071699] [PMID: 30002297]
[50]
Shanbhag, S.; Ambinder, R.F. Hodgkin lymphoma: A review and update on recent progress. CA Cancer J. Clin., 2018, 68(2), 116-132.
[http://dx.doi.org/10.3322/caac.21438] [PMID: 29194581]
[51]
Nabholtz, J.M.; Riva, A. Taxane/anthracycline combinations: setting a new standard in breast cancer? Oncologist, 2001, 6(S3)(Suppl. 3), 5-12.
[http://dx.doi.org/10.1634/theoncologist.6-suppl_3-5] [PMID: 11346678]
[52]
Rudolf, E.; Cervinka, M. Topoisomerases and tubulin inhibitors: a promising combination for cancer treatment. Curr. Med. Chem. Anticancer Agents, 2003, 3(6), 421-429.
[http://dx.doi.org/10.2174/1568011033482242] [PMID: 14529450]
[53]
Yi, J.M.; Zhang, X.F.; Huan, X.J.; Song, S.S.; Wang, W.; Tian, Q.T.; Sun, Y.M.; Chen, Y.; Ding, J.; Wang, Y.Q.; Yang, C.H.; Miao, Z.H. Dual targeting of microtubule and topoisomerase II by α-carboline derivative YCH337 for tumor proliferation and growth inhibition. Oncotarget, 2015, 6(11), 8960-8973.
[http://dx.doi.org/10.18632/oncotarget.3264] [PMID: 25840421]
[54]
Wang, L.; Fang, K.; Cheng, J.; Li, Y.; Huang, Y.; Chen, S.; Dong, G.; Wu, S.; Sheng, C. Scaffold hopping of natural product evodiamine: Discovery of a novel antitumor scaffold with excellent potency against colon cancer. J. Med. Chem., 2020, 63(2), 696-713.
[http://dx.doi.org/10.1021/acs.jmedchem.9b01626] [PMID: 31880942]
[55]
Ceramella, J.; Caruso, A.; Occhiuzzi, M.A.; Iacopetta, D.; Barbarossa, A.; Rizzuti, B.; Dallemagne, P.; Rault, S.; El-Kashef, H.; Saturnino, C.; Grande, F.; Sinicropi, M.S. Benzothienoquinazolinones as new multi-target scaffolds: Dual inhibition of human Topoisomerase I and tubulin polymerization. Eur. J. Med. Chem., 2019, 181, 111583.
[http://dx.doi.org/10.1016/j.ejmech.2019.111583] [PMID: 31400710]
[56]
Podolski-Renić A.; Banković J.; Dinić J.; Ríos-Luci, C.; Fernandes, M.X.; Ortega, N.; Kovačević-Grujičić N.; Martín, V.S.; Padrón, J.M.; Pešić M. DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells. Eur. J. Pharm. Sci., 2017, 105, 159-168.
[http://dx.doi.org/10.1016/j.ejps.2017.05.011] [PMID: 28502672]
[57]
Feng, J.; Zhang, X.; Shan, C.; Xia, J.; Zhang, Z.; Shi, H.; Leng, K.; Wu, Y.; Ji, C.; Zhong, T. Src family kinases involved in the differentiation of human preadipocytes. Mol. Cell. Endocrinol., 2021, 533, 111323.
[http://dx.doi.org/10.1016/j.mce.2021.111323] [PMID: 34000351]
[58]
Smolinski, M.P.; Bu, Y.; Clements, J.; Gelman, I.H.; Hegab, T.; Cutler, D.L.; Fang, J.W.S.; Fetterly, G.; Kwan, R.; Barnett, A.; Lau, J.Y.N.; Hangauer, D.G. Discovery of novel dual mechanism of action Src signaling and tubulin polymerization inhibitors (KX2-391 and KX2-361). J. Med. Chem., 2018, 61(11), 4704-4719.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00164] [PMID: 29617135]
[59]
Kim, S.; Min, A.; Lee, K.H.; Yang, Y.; Kim, T.Y.; Lim, J.M.; Park, S.J.; Nam, H.J.; Kim, J.E.; Song, S.H.; Han, S.W.; Oh, D.Y.; Kim, J.H.; Kim, T.Y.; Hangauer, D.; Lau, J.Y.N. Im, K.; Lee, D.S.; Bang, Y.J.; Im, S.A. Im, K.; Lee, D.S.; Bang, Y.J.; Im, S.A. Antitumor effect of KX-01 through inhibiting Src family kinases and mitosis. Cancer Res. Treat., 2017, 49(3), 643-655.
[http://dx.doi.org/10.4143/crt.2016.168] [PMID: 27737538]
[60]
Ciesielski, M.J.; Bu, Y.; Munich, S.A.; Teegarden, P.; Smolinski, M.P.; Clements, J.L.; Lau, J.Y.N.; Hangauer, D.G.; Fenstermaker, R.A. KX2-361: a novel orally bioavailable small molecule dual Src/tubulin inhibitor that provides long term survival in a murine model of glioblastoma. J. Neurooncol., 2018, 140(3), 519-527.
[http://dx.doi.org/10.1007/s11060-018-2992-4] [PMID: 30238350]
[61]
Burster, T.; Gärtner, F.; Bulach, C.; Zhanapiya, A.; Gihring, A.; Knippschild, U. Regulation of MHC I molecules in glioblastoma cells and the sensitizing of NK cells. Pharmaceuticals (Basel), 2021, 14(3), 236.
[http://dx.doi.org/10.3390/ph14030236] [PMID: 33800301]
[62]
Wells, G.; Kennedy, P.T.; Dahal, L.N. Investigating the role of indoleamine 2,3-dioxygenase in acute myeloid leukemia: A systematic review. Front. Immunol., 2021, 12, 651687.
[http://dx.doi.org/10.3389/fimmu.2021.651687] [PMID: 33777052]
[63]
Moreno, A.C.R.; Clara, R.O.; Coimbra, J.B.; Júlio, A.R.; Albuquerque, R.C.; Oliveira, E.M.; Maria-Engler, S.S.; Campa, A. The expanding roles of 1-methyl-tryptophan (1-MT): in addition to inhibiting kynurenine production, 1-MT activates the synthesis of melatonin in skin cells. FEBS J., 2013, 280(19), 4782-4792.
[http://dx.doi.org/10.1111/febs.12444] [PMID: 23879623]
[64]
Yue, E.W.; Douty, B.; Wayland, B.; Bower, M.; Liu, X.; Leffet, L.; Wang, Q.; Bowman, K.J.; Hansbury, M.J.; Liu, C.; Wei, M.; Li, Y.; Wynn, R.; Burn, T.C.; Koblish, H.K.; Fridman, J.S.; Metcalf, B.; Scherle, P.A.; Combs, A.P. Discovery of potent competitive inhibitors of indoleamine 2,3-dioxygenase with in vivo pharmacodynamic activity and efficacy in a mouse melanoma model. J. Med. Chem., 2009, 52(23), 7364-7367.
[http://dx.doi.org/10.1021/jm900518f] [PMID: 19507862]
[65]
Zhai, L.; Spranger, S.; Binder, D.C.; Gritsina, G.; Lauing, K.L.; Giles, F.J.; Wainwright, D.A. Molecular pathways: targeting IDO1 and other tryptophan dioxygenases for cancer immunotherapy. Clin. Cancer Res., 2015, 21(24), 5427-5433.
[http://dx.doi.org/10.1158/1078-0432.CCR-15-0420] [PMID: 26519060]
[66]
Crosignani, S.; Bingham, P.; Bottemanne, P.; Cannelle, H.; Cauwenberghs, S.; Cordonnier, M.; Dalvie, D.; Deroose, F.; Feng, J.L.; Gomes, B.; Greasley, S.; Kaiser, S.E.; Kraus, M.; Négrerie, M.; Maegley, K.; Miller, N.; Murray, B.W.; Schneider, M.; Soloweij, J.; Stewart, A.E.; Tumang, J.; Torti, V.R.; Van Den Eynde, B.; Wythes, M. Discovery of a novel and selective indoleamine 2,3-dioxygenase (IDO-1) inhibitor 3-(5-fluoro-1H-indol-3-yl)pyrrolidine-2,5-dione (EOS200271/PF-06840003) and its characterization as a potential clinical candidate. J. Med. Chem., 2017, 60(23), 9617-9629.
[http://dx.doi.org/10.1021/acs.jmedchem.7b00974] [PMID: 29111717]
[67]
Lu, K.; He, C.; Guo, N.; Chan, C.; Ni, K.; Weichselbaum, R.R.; Lin, W. Chlorin-based nanoscale metal-organic framework systemically rejects colorectal cancers via synergistic photodynamic therapy and checkpoint blockade immunotherapy. J. Am. Chem. Soc., 2016, 138(38), 12502-12510.
[http://dx.doi.org/10.1021/jacs.6b06663] [PMID: 27575718]
[68]
Chen, Y.; Xia, R.; Huang, Y.; Zhao, W.; Li, J.; Zhang, X.; Wang, P.; Venkataramanan, R.; Fan, J.; Xie, W.; Ma, X.; Lu, B.; Li, S. An immunostimulatory dual-functional nanocarrier that improves cancer immunochemotherapy. Nat. Commun., 2016, 7(1), 13443.
[http://dx.doi.org/10.1038/ncomms13443] [PMID: 27819653]
[69]
Muller, A.J.; DuHadaway, J.B.; Donover, P.S.; Sutanto-Ward, E.; Prendergast, G.C. Inhibition of indoleamine 2,3-dioxygenase, an immunoregulatory target of the cancer suppression gene Bin1, potentiates cancer chemotherapy. Nat. Med., 2005, 11(3), 312-319.
[http://dx.doi.org/10.1038/nm1196] [PMID: 15711557]
[70]
Li, M.; Bolduc, A.R.; Hoda, M.; Gamble, D.N.; Dolisca, S.B.; Bolduc, A.K.; Hoang, K.; Ashley, C.; McCall, D.; Rojiani, A.M.; Maria, B.L.; Rixe, O.; MacDonald, T.J.; Heeger, P.S.; Mellor, A.L.; Munn, D.H.; Johnson, T.S. The indoleamine 2,3-dioxygenase pathway controls complement-dependent enhancement of chemo-radiation therapy against murine glioblastoma. J. Immunother. Cancer, 2014, 2(1), 21-35.
[http://dx.doi.org/10.1186/2051-1426-2-21] [PMID: 25054064]
[71]
Uyttenhove, C.; Pilotte, L.; Théate, I.; Stroobant, V.; Colau, D.; Parmentier, N.; Boon, T.; Van den Eynde, B.J. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat. Med., 2003, 9(10), 1269-1274.
[http://dx.doi.org/10.1038/nm934] [PMID: 14502282]
[72]
Wang, N.; Wang, Z.; Xu, Z.; Chen, X.; Zhu, G. A cisplatin-loaded immunochemotherapeutic nanohybrid bearing immune checkpoint inhibitors for enhanced cervical cancer therapy. Angew. Chem. Int. Ed., 2018, 57(13), 3426-3430.
[http://dx.doi.org/10.1002/anie.201800422] [PMID: 29405579]
[73]
Hua, S.; Chen, F.; Wang, X.; Gou, S. Dual-functional conjugates improving cancer immunochemotherapy by inhibiting tubulin polymerization and indoleamine-2,3-dioxygenase. Eur. J. Med. Chem., 2020, 189, 112041.
[http://dx.doi.org/10.1016/j.ejmech.2020.112041] [PMID: 31954880]
[74]
Darnell, J.E. Jr. STATs and gene regulation. Science, 1997, 277(5332), 1630-1635.
[http://dx.doi.org/10.1126/science.277.5332.1630] [PMID: 9287210]
[75]
Gelain, A.; Mori, M.; Meneghetti, F.; Villa, S. Signal transducer and activator of transcription protein 3 (STAT3): an update on its direct inhibitors as promising anticancer agents. Curr. Med. Chem., 2019, 26(27), 5165-5206.
[http://dx.doi.org/10.2174/0929867325666180719122729] [PMID: 30027840]
[76]
Lai, P.S.; Rosa, D.A.; Magdy Ali, A.; Gómez-Biagi, R.F.; Ball, D.P.; Shouksmith, A.E.; Gunning, P.T. A STAT inhibitor patent review: progress since 2011. Expert Opin. Ther. Pat., 2015, 25(12), 1397-1421.
[http://dx.doi.org/10.1517/13543776.2015.1086749] [PMID: 26394986]
[77]
Zhao, E.; Shen, Y.; Amir, M.; Farris, A.B.; Czaja, M.J. Stathmin 1 induces murine hepatocyte proliferation and increased liver mass. Hepatol. Commun., 2020, 4(1), 38-49.
[http://dx.doi.org/10.1002/hep4.1447] [PMID: 31909354]
[78]
Morris, E.J.; Kawamura, E.; Gillespie, J.A.; Balgi, A.; Kannan, N.; Muller, W.J.; Roberge, M.; Dedhar, S. Stat3 regulates centrosome clustering in cancer cells via Stathmin/PLK1. Nat. Commun., 2017, 8(1), 15289.
[http://dx.doi.org/10.1038/ncomms15289] [PMID: 28474672]
[79]
Zhou, Q.; Zhu, J.; Chen, J.; Ji, P.; Qiao, C. N-arylsulfonylsubstituted-1H indole derivatives as small molecule dual inhibitors of signal transducer and activator of transcription 3 (STAT3) and tubulin. Bioorg. Med. Chem., 2018, 26(1), 96-106.
[http://dx.doi.org/10.1016/j.bmc.2017.11.023] [PMID: 29174507]
[80]
Glover, D.M.; Leibowitz, M.H.; McLean, D.A.; Parry, H. Mutations in aurora prevent centrosome separation leading to the formation of monopolar spindles. Cell, 1995, 81(1), 95-105.
[http://dx.doi.org/10.1016/0092-8674(95)90374-7] [PMID: 7720077]
[81]
Fu, J.; Bian, M.; Jiang, Q.; Zhang, C. Roles of Aurora kinases in mitosis and tumorigenesis. Mol. Cancer Res., 2007, 5(1), 1-10.
[http://dx.doi.org/10.1158/1541-7786.MCR-06-0208] [PMID: 17259342]
[82]
Lin, Y.S.; Su, L.J.; Yu, C.T.R.; Wong, F.H.; Yeh, H.H.; Chen, S.L.; Wu, J.C.; Lin, W.J.; Shiue, Y.L.; Liu, H.S.; Hsu, S.L.; Lai, J.M.; Huang, C.Y.F. Gene expression profiles of the aurora family kinases. Gene Expr., 2006, 13(1), 15-26.
[http://dx.doi.org/10.3727/000000006783991962] [PMID: 16572587]
[83]
Pollard, J.R.; Mortimore, M. Discovery and development of aurora kinase inhibitors as anticancer agents. J. Med. Chem., 2009, 52(9), 2629-2651.
[http://dx.doi.org/10.1021/jm8012129] [PMID: 19320489]
[84]
Morioka, M. 3-Cyano-6-(5-methyl-3-pyrazoloamino) pyridines (Part 2): A dual inhibitor of Aurora kinase and tubulin polymerization. Bioorg. Med. Chem. Lett., 2016, 26(24), 5860-5862.
[http://dx.doi.org/10.1016/j.bmcl.2016.11.020] [PMID: 27884697]
[85]
Devedjiev, Y.; Steussy, C.N.; Vassylyev, D.G. Crystal structure of an asymmetric complex of pyruvate dehydrogenase kinase 3 with lipoyl domain 2 and its biological implications. J. Mol. Biol., 2007, 370(3), 407-416.
[http://dx.doi.org/10.1016/j.jmb.2007.04.083] [PMID: 17532006]
[86]
Zhou, Z.H.; McCarthy, D.B.; O’Connor, C.M.; Reed, L.J.; Stoops, J.K. The remarkable structural and functional organization of the eukaryotic pyruvate dehydrogenase complexes. Proc. Natl. Acad. Sci. USA, 2001, 98(26), 14802-14807.
[http://dx.doi.org/10.1073/pnas.011597698] [PMID: 11752427]
[87]
Fujiwara, S.; Kawano, Y.; Yuki, H.; Okuno, Y.; Nosaka, K.; Mitsuya, H.; Hata, H. PDK1 inhibition is a novel therapeutic target in multiple myeloma. Br. J. Cancer, 2013, 108(1), 170-178.
[http://dx.doi.org/10.1038/bjc.2012.527] [PMID: 23321518]
[88]
Patel, M.S.; Korotchkina, L.G.; Sidhu, S. Interaction of E1 and E3 components with the core proteins of the human pyruvate dehydrogenase complex. J. Mol. Catal., B Enzym., 2009, 61(1-2), 2-6.
[http://dx.doi.org/10.1016/j.molcatb.2009.05.001] [PMID: 20160912]
[89]
Zhang, W.; Zhang, S.L.; Hu, X.; Tam, K.Y. Targeting tumor metabolism for cancer treatment: is pyruvate dehydrogenase kinases (PDKs) a viable anticancer target? Int. J. Biol. Sci., 2015, 11(12), 1390-1400.
[http://dx.doi.org/10.7150/ijbs.13325] [PMID: 26681918]
[90]
Lin, H.Y.; Han, H.W.; Sun, W.X.; Yang, Y.S.; Tang, C.Y.; Lu, G.H.; Qi, J.L.; Wang, X.M.; Yang, Y.H. Design and characterization of α-lipoic acyl shikonin ester twin drugs as tubulin and PDK1 dual inhibitors. Eur. J. Med. Chem., 2018, 144, 137-150.
[http://dx.doi.org/10.1016/j.ejmech.2017.12.019] [PMID: 29268130]
[91]
Han, Y.; Liu, D.; Li, L. PD-1/PD-L1 pathway: current researches in cancer. Am. J. Cancer Res., 2020, 10(3), 727-742.
[PMID: 32266087]
[92]
Yang, X.; Cheng, B.; Xiao, Y.; Xue, M.; Liu, T.; Cao, H.; Chen, J. Discovery of novel CA-4 analogs as dual inhibitors of tubulin polymerization and PD-1/PD-L1 interaction for cancer treatment. Eur. J. Med. Chem., 2021, 213, 113058.
[http://dx.doi.org/10.1016/j.ejmech.2020.113058] [PMID: 33280898]
[93]
Datta, S.R.; Brunet, A.; Greenberg, M.E. Cellular survival: a play in three Akts. Genes Dev., 1999, 13(22), 2905-2927.
[http://dx.doi.org/10.1101/gad.13.22.2905] [PMID: 10579998]
[94]
Altomare, D.A.; Testa, J.R. Perturbations of the AKT signaling pathway in human cancer. Oncogene, 2005, 24(50), 7455-7464.
[http://dx.doi.org/10.1038/sj.onc.1209085] [PMID: 16288292]
[95]
Revathidevi, S.; Munirajan, A.K. Akt in cancer: Mediator and more. Semin. Cancer Biol., 2019, 59, 80-91.
[http://dx.doi.org/10.1016/j.semcancer.2019.06.002] [PMID: 31173856]
[96]
Krishnegowda, G.; Prakasha Gowda, A.S.; Tagaram, H.R.S.; Carroll, K.F.S.O.; Irby, R.B.; Sharma, A.K.; Amin, S. Synthesis and biological evaluation of a novel class of isatin analogs as dual inhibitors of tubulin polymerization and Akt pathway. Bioorg. Med. Chem., 2011, 19(20), 6006-6014.
[http://dx.doi.org/10.1016/j.bmc.2011.08.044] [PMID: 21920762]
[97]
Birbo, B.; Madu, E.E.; Madu, C.O.; Jain, A.; Lu, Y. Role of HSP90 in Cancer. Int. J. Mol. Sci., 2021, 22(19), 10317.
[http://dx.doi.org/10.3390/ijms221910317] [PMID: 34638658]
[98]
Zhang, Q.; Zhai, S.; Li, L.; Li, X.; Zhou, H.; Liu, A.; Su, G.; Mu, Q.; Du, Y.; Yan, B. Anti-tumor selectivity of a novel Tubulin and HSP90 dual-targeting inhibitor in non-small cell lung cancer models. Biochem. Pharmacol., 2013, 86(3), 351-360.
[http://dx.doi.org/10.1016/j.bcp.2013.05.019] [PMID: 23743233]
[99]
Zhang, Q.; Zhai, S.; Li, L.; Li, X.; Jiang, C.; Zhang, C.; Yan, B. P-glycoprotein-evading anti-tumor activity of a novel tubulin and HSP90 dual inhibitor in a non-small-cell lung cancer model. J. Pharmacol. Sci., 2014, 126(1), 66-76.
[http://dx.doi.org/10.1254/jphs.14050FP] [PMID: 25185500]
[100]
Wang, L.; Zhang, J.; Wan, L.; Zhou, X.; Wang, Z.; Wei, W. Targeting Cdc20 as a novel cancer therapeutic strategy. Pharmacol. Ther., 2015, 151, 141-151.
[http://dx.doi.org/10.1016/j.pharmthera.2015.04.002] [PMID: 25850036]
[101]
Huang, P.; Le, X.; Huang, F.; Yang, J.; Yang, H.; Ma, J.; Hu, G.; Li, Q.; Chen, Z. Discovery of adual tubulin polymerization and cell division cycle 20 homologue inhibitor via structural modification on apcin. J. Med. Chem., 2020, 63(9), 4685-4700.
[http://dx.doi.org/10.1021/acs.jmedchem.9b02097] [PMID: 32290657]
[102]
Zhao, J.C.; Agarwal, S.; Ahmad, H.; Amin, K.; Bewersdorf, J.P.; Zeidan, A.M. A review of FLT3 inhibitors in acute myeloid leukemia. Blood Rev., 2022, 52, 100905.
[http://dx.doi.org/10.1016/j.blre.2021.100905] [PMID: 34774343]
[103]
Daver, N.; Schlenk, R.F.; Russell, N.H.; Levis, M.J. Targeting FLT3 mutations in AML: review of current knowledge and evidence. Leukemia, 2019, 33(2), 299-312.
[http://dx.doi.org/10.1038/s41375-018-0357-9] [PMID: 30651634]
[104]
Malik, H.S.; Bilal, A.; Ullah, R.; Iqbal, M.; Khan, S.; Ahmed, I.; Krohn, K.; Saleem, R.S.Z.; Hussain, H.; Faisal, A. Natural and semisynthetic chalcones as dual FLT3 andmicrotubule polymerization inhibitors. J. Nat. Prod., 2020, 83(10), 3111-3121.
[http://dx.doi.org/10.1021/acs.jnatprod.0c00699] [PMID: 32975953]
[105]
Pandey, K.; An, H.J.; Kim, S.K.; Lee, S.A.; Kim, S.; Lim, S.M.; Kim, G.M.; Sohn, J.; Moon, Y.W. Molecular mechanisms of resistance to CDK4/6 inhibitors in breast cancer: A review. Int. J. Cancer, 2019, 145(5), 1179-1188.
[http://dx.doi.org/10.1002/ijc.32020] [PMID: 30478914]
[106]
Sonawane, V.; Mohd Siddique, M.U.; Jadav, S.S.; Sinha, B.N.; Jayaprakash, V.; Chaudhuri, B. Cink4T, a quinazolinone-based dual inhibitor of Cdk4 and tubulin polymerization, identified via ligand-based virtual screening, for efficient anticancer therapy. Eur. J. Med. Chem., 2019, 165, 115-132.
[http://dx.doi.org/10.1016/j.ejmech.2019.01.011] [PMID: 30665142]
[107]
Mahale, S.; Bharate, S.B.; Manda, S.; Joshi, P.; Jenkins, P.R.; Vishwakarma, R.A.; Chaudhuri, B. Antitumour potential of BPT: a dual inhibitor of cdk4 and tubulin polymerization. Cell Death Dis., 2015, 6(5), e1743.
[http://dx.doi.org/10.1038/cddis.2015.96] [PMID: 25950473]
[108]
Mahale, S.; Bharate, S.B.; Manda, S.; Joshi, P.; Bharate, S.S.; Jenkins, P.R.; Vishwakarma, R.A.; Chaudhuri, B. Biphenyl-4-carboxylic acid [2-(1H-indol-3-yl)-ethyl]-methylamide (CA224), a nonplanar analogue of fascaplysin, inhibits Cdk4 and tubulin polymerization: evaluation of in vitro and in vivo anticancer activity. J. Med. Chem., 2014, 57(22), 9658-9672.
[http://dx.doi.org/10.1021/jm5014743] [PMID: 25368960]
[109]
Mahale, S.; Aubry, C.; Jenkins, P.R.; Maréchal, J.D.; Sutcliffe, M.J.; Chaudhuri, B. Inhibition of cancer cell growth by cyclin dependent kinase 4 inhibitors synthesized based on the structure of fascaplysin. Bioorg. Chem., 2006, 34(5), 287-297.
[http://dx.doi.org/10.1016/j.bioorg.2006.06.004] [PMID: 16904725]
[110]
Mi, L.; Gan, N.; Cheema, A.; Dakshanamurthy, S.; Wang, X.; Yang, D.C.H.; Chung, F.L. Cancer preventive isothiocyanates induce selective degradation of cellular alpha- and beta-tubulins by proteasomes. J. Biol. Chem., 2009, 284(25), 17039-17051.
[http://dx.doi.org/10.1074/jbc.M901789200] [PMID: 19339240]
[111]
Harris, G.; Schaefer, K.L. The microtubule-targeting agent T0070907 induces proteasomal degradation of tubulin. Biochem. Biophys. Res. Commun., 2009, 388(2), 345-349.
[http://dx.doi.org/10.1016/j.bbrc.2009.08.009] [PMID: 19665001]
[112]
Yang, J.; Li, Y.; Yan, W.; Li, W.; Qiu, Q.; Ye, H.; Chen, L. Covalent modification of Cys-239 in β-tubulin by small molecules as a strategy to promote tubulin heterodimer degradation. J. Biol. Chem., 2019, 294(20), 8161-8170.
[http://dx.doi.org/10.1074/jbc.RA118.006325] [PMID: 30940730]
[113]
Alhosin, M.; Ibrahim, A.; Boukhari, A.; Sharif, T.; Gies, J.P.; Auger, C.; Schini-Kerth, V.B. Anti-neoplastic agent thymoquinone induces degradation of α and β tubulin proteins in human cancer cells without affecting their level in normal human fibroblasts. Invest. New Drugs, 2012, 30(5), 1813-1819.
[http://dx.doi.org/10.1007/s10637-011-9734-1] [PMID: 21881916]
[114]
Gasic, I.; Groendyke, B.J.; Nowak, R.P.; Yuan, J.C.; Kalabathula, J.; Fischer, E.S.; Gray, N.S.; Mitchison, T.J. Tubulin resists degradation by cereblon-recruiting PROTACs. Cells, 2020, 9(5), 1083.
[http://dx.doi.org/10.3390/cells9051083] [PMID: 32349222]

Rights & Permissions Print Cite
Article Metrics
43
2
Wayfinder Image
Open Access Journals Promotions
World Antimicrobial Awareness Week
© 2024 Bentham Science Publishers | Privacy Policy