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Review

Development of tubulin polymerization inhibitors as anticancer agents

, &
Pages 797-820 | Received 17 May 2023, Accepted 01 Dec 2023, Published online: 11 Dec 2023

References

  • Janke C, Magiera MM. The tubulin code and its role in controlling microtubule properties and functions. Nat Rev Mol Cell Biol. 2020;21(6):307–326. doi: 10.1038/s41580-020-0214-3
  • Rowinsky EK, Calvo E. Novel agents that target tublin and related elements. Semin Oncol. 2006;33(4):421–435. doi: 10.1053/j.seminoncol.2006.04.006
  • Peerzada MN, Hamel E, Bai R, et al. Deciphering the key heterocyclic scaffolds in targeting microtubules, kinases and carbonic anhydrases for cancer drug development. Pharmacol Ther. 2021;225:107860. doi: 10.1016/j.pharmthera.2021.107860
  • Logan CM, Menko AS. Microtubules: Evolving roles and critical cellular interactions. Exp Biol Med. 2019;244:1240–1254. doi: 10.1177/1535370219867296
  • Dumontet C, Jordan MA. Microtubule-binding agents: a dynamic field of cancer therapeutics. Nat Rev Drug Discov. 2010;9(10):790–803. doi: 10.1038/nrd3253
  • Mukhtar E, Adhami VM, Mukhtar H. Targeting microtubules by natural agents for cancer therapy. Mol Cancer Ther. 2014;13(2):275–284. doi: 10.1158/1535-7163.MCT-13-0791
  • Fojo T, Menefee M. Mechanisms of multidrug resistance: the potential role of microtubule-stabilizing agents. Ann Oncol. 2007;18:3–8. doi: 10.1093/annonc/mdm172
  • Stiller CA. International patterns of cancer incidence in adolescents. Cancer Treat Rev. 2007;33(7):631–645. doi: 10.1016/j.ctrv.2007.01.001
  • Arnst KE, Banerjee S, Chen H, et al. Current advances of tubulin inhibitors as dual acting small molecules for cancer therapy. Med Res Rev. 2019;39(4):1398–1426. doi: 10.1002/med.21568
  • Schiff PB, Fant J, Horwitz SB. Promotion of microtubule assembly in vitro by taxol. Nature. 1979;277(5698):665–667. doi: 10.1038/277665a0
  • Bollag DM, McQueney PA, Zhu J, et al. Epothilones, a new class of microtubule-stabilizing agents with a taxol-like mechanism of action. Cancer Res. 1995;55:2325–2333.
  • Nogales E, Wolf SG, Khan IA, et al. Structure of tubulin at 6.5 a and location of the taxol-binding site. Nature. 1995;375:424–427. doi: 10.1038/375424a0
  • Pryor DE, O’Brate A, Bilcer G, et al. The microtubule stabilizing agent laulimalide does not bind in the taxoid site, kills cells resistant to paclitaxel and epothilones, and may not require its epoxide moiety for activity. Biochemistry. 2002;41(29):9109–9115. doi: 10.1021/bi020211b
  • Prota AE, Bargsten K, Northcote PT, et al. Structural basis of microtubule stabilization by laulimalide and peloruside A. Angew Chem Int Ed Engl. 2014;53(6):1621–1625. doi: 10.1002/anie.201307749
  • Hamel E, Day BW, Miller JH, et al. Synergistic effects of peloruside a and laulimalide with taxoid site drugs, but not with each other, on tubulin assembly. Mol Pharmacol. 2006;70(5):1555–1564. doi: 10.1124/mol.106.027847
  • Coderch C, Morreale A, Gago F. Tubulin-based structure-affinity relationships for Antimitotic Vinca Alkaloids. Anticancer Agents Med Chem. 2012;12(3):219–225. doi: 10.2174/187152012800228841
  • Bai R, Nguyen TL, Burnett JC, et al. Interactions of halichondrin B and Eribulin with tubulin. J Chem Inf Model. 2011;51(6):1393–1404. doi: 10.1021/ci200077t
  • Avendaño C, Menéndez JC. Anticancer Drugs Targeting Tubulin and Microtubules. Med Chem Anticancer Drugs Elsevier. 2015;359–390. doi: 10.1016/B978-0-444-62649-3.00009-0
  • Gigant B, Wang C, Ravelli RBG, et al. Structural basis for the regulation of tubulin by vinblastine. Nature. 2005;435(7041):519–522. doi: 10.1038/nature03566
  • Svoboda G, Johnson I, Gorman M, et al. Current status of research on the alkaloids of vinca rosea Linn. (catharanthus roseus G Don). J Pharm Sci. 1962;51:707–720. doi: 10.1002/jps.2600510802
  • Chen S-H, Hong J. Novel tubulin interacting agents: a tale of Taxus brevifolia and Catharanthus roseus-based drug discovery. Drugs Future. 2006;31:123. doi: 10.1358/dof.2006.031.02.953585
  • Cruz-Monserrate Z, Vervoort HC, Bai R, et al. Diazonamide a and a synthetic structural analog: disruptive effects on mitosis and cellular microtubules and analysis of their interactions with tubulin. Mol Pharmacol. 2003;63(6):1273–1280. doi: 10.1124/mol.63.6.1273
  • Pera B, Barasoain I, Pantazopoulou A, et al. New interfacial microtubule inhibitors of marine origin, PM050489/PM060184, with potent antitumor activity and a distinct mechanism. ACS Chem Biol. 2013;8(9):2084–2094. doi: 10.1021/cb400461j
  • Cormier A, Marchand M, Ravelli RBG, et al. Structural insight into the inhibition of tubulin by vinca domain peptide ligands. EMBO Rep. 2008;9:1101–1106. doi: 10.1038/embor.2008.171
  • Wang Y, Benz FW, Wu Y, et al. Structural insights into the pharmacophore of vinca domain inhibitors of microtubules. Mol Pharmacol. 2016;89(2):233–242. doi: 10.1124/mol.115.100149
  • Waight AB, Bargsten K, Doronina S, et al. Structural Basis of Microtubule Destabilization by Potent Auristatin Anti-Mitotics. PLoS One. 2016;11(8):0160890. doi: 10.1371/journal.pone.0160890
  • Bai R, Edler MC, Bonate PL, et al. Intracellular activation and deactivation of tasidotin, an analog of dolastatin 15: correlation with cytotoxicity. Mol Pharmacol. 2009;75(1):218–226. doi: 10.1124/mol.108.051110
  • Cruz-Monserrate Z, Mullaney JT, Harran PG, et al. Dolastatin 15 binds in the vinca domain of tubulin as demonstrated by Hummel-Dreyer chromatography. Eur J Biochem. 2003;270:3822–3828. doi: 10.1046/j.1432-1033.2003.03776.x
  • Wieczorek M, Tcherkezian J, Bernier C, et al. The synthetic diazonamide DZ-2384 has distinct effects on microtubule curvature and dynamics without neurotoxicity. Sci Transl Med. 2016;8(365):365. doi: 10.1126/scitranslmed.aag1093
  • Bai R, Cruz-Monserrate Z, Fenical W, et al. Interaction of diazonamide a with tubulin. Arch Biochem Biophys. 2020;680:108217. doi: 10.1016/j.abb.2019.108217
  • Dabydeen DA, Burnett JC, Bai R, et al. Comparison of the activities of the truncated halichondrin B analog NSC 707389 (E7389) with those of the parent compound and a proposed binding site on tubulin. Mol Pharmacol. 2006;70(6):1866–1875. doi: 10.1124/mol.106.026641
  • Doodhi H, Prota AE, Rodríguez-García R, et al. Termination of protofilament elongation by Eribulin induces lattice defects that promote microtubule catastrophes. Curr Biol. 2016;26(13):1713–1721. doi: 10.1016/j.cub.2016.04.053
  • Beyer CF, Zhang N, Hernandez R, et al. TTI-237: a novel microtubule-active compound with in vivo antitumor activity. Cancer Res. 2008;68(7):2292–2300. doi: 10.1158/0008-5472.CAN-07-1420
  • Sáez-Calvo G, Sharma A, de Asís Balaguer F, et al. Triazolopyrimidines Are Microtubule-Stabilizing Agents that Bind the Vinca Inhibitor Site of Tubulin. Cell Chem Biol. 2017;24:737–750. doi: 10.1016/j.chembiol.2017.05.016
  • Prota AE, Bargsten K, Diaz JF, et al. A new tubulin-binding site and pharmacophore for microtubule-destabilizing anticancer drugs. Proc Natl Acad Sci U S A. 2014;111(38):13817–13821. doi: 10.1073/pnas.1408124111
  • Yang J, Wang Y, Wang T, et al. Pironetin reacts covalently with cysteine-316 of α-tubulin to destabilize microtubule. Nat Commun. 2016;7(1):12103. doi: 10.1038/ncomms12103
  • Prota AE, Setter J, Waight AB, et al. 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. doi: 10.1016/j.jmb.2016.06.023
  • Lu Y, Chen J, Xiao M, et al. An overview of tubulin inhibitors that interact with the colchicine binding site. Pharm Res. 2012;29(11):2943–2971. doi: 10.1007/s11095-012-0828-z
  • Aubin JE, Carlsen SA, Ling V. Colchicine permeation is required for inhibition of concanavalin a capping in Chinese hamster ovary cells. Proc Natl Acad Sci. 1975;72(11):4516–4520. doi: 10.1073/pnas.72.11.4516
  • Pettit GR, Singh SB, Hamel E, et al. Isolation and structure of the strong cell growth and tubulin inhibitor combretastatin A-4. Experientia. 1989;45(2):209–211. doi: 10.1007/BF01954881
  • Dark GG, Hill SA, Prise VE, et al. Combretastatin A-4, an agent that displays potent and selective toxicity toward tumor vasculature. Cancer Res. 1997;57:1829–1834.
  • Gaspari R, Prota AE, Bargsten K, et al. Structural basis of cis- and trans-combretastatin binding to tubulin. Chem. 2017;2(1):102–113. doi: 10.1016/j.chempr.2016.12.005
  • Meleti VR, Esperandim VR, Flauzino LGB, et al. (±)-licarin a and its semi-synthetic derivatives: in vitro and in silico evaluation of trypanocidal and schistosomicidal activities. Acta Trop. 2020;202:105248. doi: 10.1016/j.actatropica.2019.105248
  • Sosa JA, Elisei R, Jarzab B, et al. A randomized phase II/III trial of a tumor vascular disrupting agent fosbretabulin tromethamine (CA4P) with carboplatin (C) and paclitaxel (P) in anaplastic thyroid cancer (ATC): final survival analysis for the FACT trial. J Clin Oncol. 2011;29(15_suppl):5502–5502. doi: 10.1200/jco.2011.29.15_suppl.5502
  • Chase DM, Chaplin DJ, Monk BJ. The development and use of vascular targeted therapy in ovarian cancer. Gynecol Oncol. 2017;145(2):393–406. doi: 10.1016/j.ygyno.2017.01.031
  • Blay J-Y, Pápai Z, Tolcher AW, et al. Ombrabulin plus cisplatin versus placebo plus cisplatin in patients with advanced soft-tissue sarcomas after failure of anthracycline and ifosfamide chemotherapy: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2015;16(5):531–540. doi: 10.1016/S1470-2045(15)70102-6
  • Deng S, Krutilina RI, Hartman KL, et al. Colchicine-binding site agent CH-2-77 as a potent tubulin inhibitor suppressing triple-negative breast cancer. Mol Cancer Ther. 2022;21(7):1103–1114. doi: 10.1158/1535-7163.MCT-21-0899
  • Sekar P, Ravitchandirane R, Khanam S, et al. Novel molecules as the emerging trends in cancer treatment: an update. Med Oncol. 2022;39(2):20. doi: 10.1007/s12032-021-01615-6
  • Stengel C, Newman SP, Leese MP, et al. Class III β-tubulin expression and in vitro resistance to microtubule targeting agents. Br J Cancer. 2010;102(2):316–324. doi: 10.1038/sj.bjc.6605489
  • Waghray D, Zhang Q. Inhibit or Evade Multidrug Resistance P-Glycoprotein in Cancer Treatment. J Med Chem. 2018;61(12):5108–5121. doi: 10.1021/acs.jmedchem.7b01457
  • McLoughlin EC, O’Boyle NM. Colchicine-binding site inhibitors from chemistry to clinic: a review. Pharmaceuticals. 2020;13(1):8. doi: 10.3390/ph13010008
  • Sharom FJ. Complex Interplay between the P-Glycoprotein Multidrug Efflux Pump and the Membrane: Its Role in Modulating Protein Function. Front Oncol. 2014;4:4. doi: 10.3389/fonc.2014.00041
  • Deng S, Banerjee S, Chen H, et al. SB226, an inhibitor of tubulin polymerization, inhibits paclitaxel-resistant melanoma growth and spontaneous metastasis. Cancer Lett. 2023;555:216046. doi: 10.1016/j.canlet.2022.216046
  • Kang Y, Pei Y, Qin J, et al. Design, synthesis, and biological activity evaluation of novel tubulin polymerization inhibitors based on pyrimidine ring skeletons. Bioorg Med Chem Lett. 2023;84:129195. doi: 10.1016/j.bmcl.2023.129195
  • Laxmikeshav K, Sharma P, Palepu M, et al. Benzimidazole based bis-carboxamide derivatives as promising cytotoxic agents: design, synthesis, in silico and tubulin polymerization inhibition. J Mol Struct. 2023;1271:134078. doi: 10.1016/j.molstruc.2022.134078
  • Pochampally S, Hartman KL, Wang R, et al. Design, synthesis, and biological evaluation of pyrimidine dihydroquinoxalinone derivatives as tubulin colchicine site-binding agents that displayed potent anticancer activity both in vitro and in vivo. ACS Pharmacol Transl Sci. 2023;6(4):526–545. doi: 10.1021/acsptsci.2c00108
  • Amin MM, Abuo-Rahma G-D, Shaykoon MSA, et al. Design, synthesis, cytotoxic activities, and molecular docking of chalcone hybrids bearing 8-hydroxyquinoline moiety with dual tubulin/EGFR kinase inhibition. Bioorg Chem. 2023;134:106444. doi: 10.1016/j.bioorg.2023.106444
  • Li G, Wu J-Q, Cai X, et al. Design, synthesis, and biological evaluation of diaryl heterocyclic derivatives targeting tubulin polymerization with potent anticancer activities. Eur J Med Chem. 2023;252:115284. doi: 10.1016/j.ejmech.2023.115284
  • Abdul Hussein SA, Razzak Mahmood AA, Tahtamouni LH, et al. New combretastatin analogs as anticancer agents: design, synthesis, microtubules polymerization inhibition, and molecular docking studies. Chem Biodivers. 2023;20(4):202201206. doi: 10.1002/cbdv.202201206
  • John SE, Sharma A, Gulati S, et al. Synthesis of cis -stilbene-based 1,2,4-triazole/1,3,4-oxadiazole conjugates as potential cytotoxic and tubulin polymerization inhibitors. New J Chem. 2023;(47):4687–4697. doi: 10.1039/D2NJ04955D
  • Huo X-S, Jian X-E, Ou-Yang J, et al. Discovery of highly potent tubulin polymerization inhibitors: design, synthesis, and structure-activity relationships of novel 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidines. Eur J Med Chem. 2021;220(220):113449. doi: 10.1016/j.ejmech.2021.113449
  • Sun Y-X, Song J, Kong L-J, et al. Design, synthesis and evaluation of novel bis-substituted aromatic amide dithiocarbamate derivatives as colchicine site tubulin polymerization inhibitors with potent anticancer activities. Eur J Med Chem. 2022;229:114069. doi: 10.1016/j.ejmech.2021.114069
  • Wang G, Liu W, Gong Z, et al. Design, synthesis, biological evaluation and molecular docking studies of new chalcone derivatives containing diaryl ether moiety as potential anticancer agents and tubulin polymerization inhibitors. Bioorg Chem. 2020;95:103565. doi: 10.1016/j.bioorg.2019.103565
  • Kode J, Kovvuri J, Nagaraju B, et al. Synthesis, biological evaluation, and molecular docking analysis of phenstatin based indole linked chalcones as anticancer agents and tubulin polymerization inhibitors. Bioorg Chem. 2020;105:104447. doi: 10.1016/j.bioorg.2020.104447
  • Rahimzadeh Oskuei S, Mirzaei S, Jafari-Nik MR, et al. Design, synthesis and biological evaluation of novel imidazole-chalcone derivatives as potential anticancer agents and tubulin polymerization inhibitors. Bioorg Chem. 2021;112:104904. doi: 10.1016/j.bioorg.2021.104904
  • Li G, Wang Y, Li L, et al. Design, synthesis, and bioevaluation of pyrazolo[1,5-a]pyrimidine derivatives as tubulin polymerization inhibitors targeting the colchicine binding site with potent anticancer activities. Eur J Med Chem. 2020;202:112519. doi: 10.1016/j.ejmech.2020.112519
  • Sana S, Tokala R, Bajaj DM, et al. Design and synthesis of substituted dihydropyrimidinone derivatives as cytotoxic and tubulin polymerization inhibitors. Bioorg Chem. 2019;93:103317. doi: 10.1016/j.bioorg.2019.103317
  • Diao P-C, Jian X-E, Chen P, et al. Design, synthesis and biological evaluation of novel indole-based oxalamide and aminoacetamide derivatives as tubulin polymerization inhibitors. Bioorg Med Chem Lett. 2020;30(2):126816. doi: 10.1016/j.bmcl.2019.126816
  • Perin N, Hok L, Beč A, et al. N-substituted benzimidazole acrylonitriles as in vitro tubulin polymerization inhibitors: synthesis, biological activity and computational analysis. Eur J Med Chem. 2021;211:113003. doi: 10.1016/j.ejmech.2020.113003
  • Romagnoli R, Oliva P, Prencipe F, et al. Design, synthesis and biological investigation of 2-anilino Triazolopyrimidines as tubulin polymerization inhibitors with anticancer activities. Pharmaceuticals. 2022;15(8):1031. doi: 10.3390/ph15081031
  • Oliva P, Romagnoli R, Manfredini S, et al. Design, synthesis, in vitro and in vivo biological evaluation of 2-amino-3-aroylbenzo[b]furan derivatives as highly potent tubulin polymerization inhibitors. Eur J Med Chem. 2020;200:112448. doi: 10.1016/j.ejmech.2020.112448
  • Romagnoli R, Oliva P, Salvador MK, et al. Design, synthesis and biological evaluation of novel vicinal diaryl-substituted 1H-Pyrazole analogues of combretastatin A-4 as highly potent tubulin polymerization inhibitors. Eur J Med Chem. 2019;181:111577. doi: 10.1016/j.ejmech.2019.111577.
  • Romagnoli R, Prencipe F, Oliva P, et al. Design, synthesis and biological evaluation of 2-alkoxycarbonyl-3-anilinoindoles as a new class of potent inhibitors of tubulin polymerization. Bioorg Chem. 2020;97:103665. doi: 10.1016/j.bioorg.2020.103665
  • Kazan F, Yagci ZB, Bai R, et al. Synthesis and biological evaluation of indole-2-carbohydrazides and thiazolidinyl-indole-2-carboxamides as potent tubulin polymerization inhibitors. Comput Biol Chem. 2019;80:512–523. doi: 10.1016/j.compbiolchem.2019.05.002
  • Hawash M, Kahraman DC, Olgac A, et al. Design and synthesis of novel substituted indole-acrylamide derivatives and evaluation of their anti-cancer activity as potential tubulin-targeting agents. J Mol Struct. 2022;1254:132345. doi: 10.1016/j.molstruc.2022.132345
  • Spanò V, Barreca M, Rocca R, et al. Insight on [1,3]thiazolo[4,5-e]isoindoles as tubulin polymerization inhibitors. Eur J Med Chem. 2021;212:113122. doi: 10.1016/j.ejmech.2020.113122
  • Romagnoli R, Prencipe F, Oliva P, et al. 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. doi: 10.1021/acs.jmedchem.8b01391
  • Islam F, Quadery TM, Bai R, et al. Novel pyrazolo[4,3-d]pyrimidine microtubule targeting agents (MTAs): synthesis, structure–activity relationship, in vitro and in vivo evaluation as antitumor agents. Bioorg Med Chem Lett. 2021;41:127923. doi: 10.1016/j.bmcl.2021.127923
  • Oliva P, Romagnoli R, Cacciari B, et al. Synthesis and Biological Evaluation of Highly Active 7-Anilino Triazolopyrimidines as Potent Antimicrotubule Agents. Pharmaceutics. 2022;14(6):1191. doi: 10.3390/pharmaceutics14061191
  • Hawash M, Ergun SG, Kahraman DC, et al. Novel indole-pyrazole hybrids as potential tubulin-targeting agents; synthesis, antiproliferative evaluation, and molecular modeling studies. J Mol Struct. 2023;1285:135477. doi: 10.1016/j.molstruc.2023.135477
  • Khodyuk RGD, Bai R, Hamel E, et al. Diaryl disulfides and thiosulfonates as combretastatin A-4 analogues: synthesis, cytotoxicity and antitubulin activity. Bioorg Chem. 2020;101:104017. doi: 10.1016/j.bioorg.2020.104017
  • Romagnoli R, Prencipe F, Oliva P, et al. Synthesis and biological evaluation of new antitubulin agents containing 2-(3′,4′,5′-trimethoxyanilino)-3,6-disubstituted-4,5,6,7-tetrahydrothieno[2,3-c]pyridine scaffold. Molecules. 2020;25:1690. doi: 10.3390/molecules25071690
  • Romagnoli R, Oliva P, Salvador MK, et al. A facile synthesis of diaryl pyrroles led to the discovery of potent colchicine site antimitotic agents. Eur J Med Chem. 2021;214:113229. doi: 10.1016/j.ejmech.2021.113229
  • Puxeddu M, Wu J, Bai R, et al. Induction of ferroptosis in Glioblastoma and ovarian cancers by a new pyrrole tubulin assembly inhibitor. J Med Chem. 2022;65(23):15805–15818. Internet. doi: 10.1021/acs.jmedchem.2c01457
  • Spanò V, Rocca R, Barreca M, et al. Pyrrolo[2′,3′: 3,4]cyclohepta[1,2- d][1,2]oxazoles, a new class of antimitotic agents active against multiple malignant cell types. J Med Chem. 2020;63:12023–12042. doi: 10.1021/acs.jmedchem.0c01315
  • Chen L, Ji T-Y, Huo X-S, et al. Rational design, synthesis and biological evaluation of novel 2-(substituted amino)-[1,2,4]triazolo[1,5-a]pyrimidines as novel tubulin polymerization inhibitors. Eur J Med Chem. 2022;244:114864. doi: 10.1016/j.ejmech.2022.114864
  • Sebastiani J, Puxeddu M, Nalli M, et al. RS6077 induces mitotic arrest and selectively activates cell death in human cancer cell lines and in a lymphoma tumor in vivo. Eur J Med Chem. 2023;246:114997. doi: 10.1016/j.ejmech.2022.114997
  • Li W, Xu F, Shuai W, et al. Discovery of novel quinoline–chalcone derivatives as potent antitumor agents with microtubule polymerization inhibitory activity. J Med Chem. 2019;62(2):993–1013. doi: 10.1021/acs.jmedchem.8b01755
  • Zhu H, Li W, Shuai W, et al. Discovery of novel N-benzylbenzamide derivatives as tubulin polymerization inhibitors with potent antitumor activities. Eur J Med Chem. 2021;216:113316. doi: 10.1016/j.ejmech.2021.113316
  • Zhu H, Tan Y, He C, et al. Discovery of a novel vascular disrupting agent inhibiting tubulin polymerization and HDACs with potent antitumor effects. J Med Chem. 2022;65(16):11187–11213. doi: 10.1021/acs.jmedchem.2c00681
  • Ogitani Y, Ishii C, Kamai Y, et al. Combination of antibody–drug conjugate and tubulin inhibitor. Tokyo (JP). 2021. (US2021/0290775A1).
  • Peto CJ, Jablons DM, Tsang T, et al. Phthalazine derivatives as inhibitors of parp1, parp2, and/or tubulin useful for the treatment of cancer. (US10640493B2). Oakland CA USA: The regents of the University of California, Atlasmedx, Inc; 2020.
  • Alami M, Provot O, Hamze A, et al. Compounds with tubulin polymerization inhibitory activity and immunomodulatory properties. (US2021/0230140A1). Saint Aubin (FR): Universite Paris Saclay; 2021.
  • Wang G, Zheng S, Orleans N, et al. Anti-vasculature and anti–tubulin combretastatin analogs for treatment of cancer. (US10017475B2). New Orleans LA USA: Xavier University of Louisiana; 2018.
  • Alami M, Hamze A, Brion J-D, et al. “Multi-target” compounds with inhibitory activity towards histone deacetylases and tubulin polymerization, for use in the treatment of cancer. Orsay (FR): Université Paris-Saclay; 2021.
  • Torres J, Damoiseaux R, Yeates TO, et al. Tubulin-binding compounds, compositions and uses related thereto. (US10913750B2). Oakland CA (US): The Regents of the University of California; 2021.
  • Zeqing B. Dual-target inhibitors of tubulin histone deacetylase and their uses. CN: Zhaoqing Medical College; 2022. (CN202210632565.6A).
  • Yuxi W. (2- (1H-indole-3-yl) -1H- imidazole-4-yl) phenyl ketone compound and application thereof. CN: Guangdong Chenkang Biotechnology Co ltd; 2022. (CN114751891B).
  • Xuejun Z, Yang Z, Hui Y, et al. Wuhan humanwell innovative drug res and development center limited company. “Diaryl compound as tubulin/src dual target inhibitor. CN: Wuhan Renfu Innovation Drug Res and Development Center Co Ltd; 2023. (CN116444427A).
  • Alami M, Provot O, Hamze A, et al. Compounds with tubulin polymerisation inhibitory activity and immunomodulatory properties. US: Universite Paris-Saclay; 2023. (US20230203005A1).
  • Huang L, Khedkar SA, Steinmetz MO, et al. Tubulin binding compounds and therapeutic use thereof. (NY) (US): BeyondSpring Pharmaceuticals, Inc; 2023. (US11633393B2).
  • Krutilina KLH, Oluwalana D, Playa HC, et al. Sabizabulin, a potent orally bioavailable colchicine binding site agent, suppresses HER2+ breast cancer and metastasis. Cancers (Basel). 2022;14:5336. doi: 10.3390/cancers14215336
  • Dhasmana AKM, Khoja UB, Mishra S. Molecular structure, spectral analysis and chemical activity of sabizabulin: A computational study. J Mol Graph Model. 2023;125:108618. doi: 10.1016/j.jmgm.2023.108618
  • Bissonnette RP, Carlsbad AR, Goodenow R, et al. Combination therapies of hdac inhibitors and tubulin inhibitors. San Diego, CA, USA: HUYA BIOSCIENCE INT LLC; 2019. (US2019/0046513A1)
  • Gangjee A. Substituted bicyclic pyrimidine compounds with tubulin an multiple receptor inhibition. (US10906910B2). Pittsburgh PA US A: Duquesne University of the Holy Spirit; 2021.
  • Liu Z, Liu Y, Shi Y, et al. Design, synthesis, and biological evaluation of 1-methyl-1,4-dihyrdoindeno [1,2-c] pyrazole analogues as potential anticaner agents targeting tubulin colchicine binding site. (US10906910B2). Jinan Shandong CN: Act Pharma CO., LTD; 2021.

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