tubulin modulators


Summary: Agents that interact with TUBULIN to inhibit or promote polymerization of MICROTUBULES.

Top Publications

  1. Zaninetti R, Cortese S, Aprile S, Massarotti A, Canonico P, Sorba G, et al. A concise synthesis of pyrazole analogues of combretastatin A1 as potent anti-tubulin agents. ChemMedChem. 2013;8:633-43 pubmed publisher
  2. Zheng Z, Wan Q, Liu J, Zhu H, Chu X, Du Q. Evidence for dynein and astral microtubule-mediated cortical release and transport of G?i/LGN/NuMA complex in mitotic cells. Mol Biol Cell. 2013;24:901-13 pubmed publisher
    ..We propose that regulated cortical release and transport of LGN complex along astral microtubules may contribute to spindle positioning in mammalian cells. ..
  3. Ehteda A, Galettis P, Chu S, Pillai K, Morris D. Complexation of albendazole with hydroxypropyl-?-cyclodextrin significantly improves its pharmacokinetic profile, cell cytotoxicity and antitumor efficacy in nude mice. Anticancer Res. 2012;32:3659-66 pubmed
    ..Therefore, the aim of this study was to formulate ABZ with acetic acid/2-hydroxypropyl-?-cyclodextrin (HP?CD) with the view of improving its aqueous solubility and therefore, its antitumor efficacy...
  4. Prota A, Bargsten K, Zurwerra D, Field J, Díaz J, Altmann K, et al. Molecular mechanism of action of microtubule-stabilizing anticancer agents. Science. 2013;339:587-90 pubmed publisher
    ..Further, our results offer fundamental structural insights into the control mechanisms of microtubule dynamics. ..
  5. Romagnoli R, Baraldi P, Salvador M, Preti D, Aghazadeh Tabrizi M, Brancale A, et al. Discovery and optimization of a series of 2-aryl-4-amino-5-(3',4',5'-trimethoxybenzoyl)thiazoles as novel anticancer agents. J Med Chem. 2012;55:5433-45 pubmed publisher
    ..Furthermore, compound 3b significantly reduced the growth of the HT-29 xenograft in a nude mouse model, suggesting that 3b is a promising new antimitotic agent with clinical potential. ..
  6. Barten D, Fanara P, Andorfer C, Hoque N, Wong P, Husted K, et al. Hyperdynamic microtubules, cognitive deficits, and pathology are improved in tau transgenic mice with low doses of the microtubule-stabilizing agent BMS-241027. J Neurosci. 2012;32:7137-45 pubmed publisher
    ..Together, these data suggest that tau-mediated loss of MT stability may contribute to disease progression and that very low doses of BMS-241027 may be useful in the treatment of AD and other tauopathies...
  7. Matson D, Demirel P, Stukenberg P, Burke D. A conserved role for COMA/CENP-H/I/N kinetochore proteins in the spindle checkpoint. Genes Dev. 2012;26:542-7 pubmed publisher
    ..We propose a model to explain the differential response of human cells to nocodazole and paclitaxel...
  8. Zhang B, Carroll J, Trojanowski J, Yao Y, Iba M, Potuzak J, et al. The microtubule-stabilizing agent, epothilone D, reduces axonal dysfunction, neurotoxicity, cognitive deficits, and Alzheimer-like pathology in an interventional study with aged tau transgenic mice. J Neurosci. 2012;32:3601-11 pubmed publisher
    ..These data reveal that brain-penetrant MT-stabilizing drugs hold promise for the treatment of AD and related tauopathies, and that EpoD could be a candidate for clinical testing. ..
  9. Lu Y, Chen J, Xiao M, Li W, Miller D. An overview of tubulin inhibitors that interact with the colchicine binding site. Pharm Res. 2012;29:2943-71 pubmed publisher
    ..The present review is a synopsis of compounds that have been reported in the past decade that have provided an increase in our understanding of the actions of CBSIs. ..

More Information


  1. Wang X, Ohkoshi E, Wang S, Hamel E, Bastow K, Morris Natschke S, et al. Synthesis and biological evaluation of N-alkyl-N-(4-methoxyphenyl)pyridin-2-amines as a new class of tubulin polymerization inhibitors. Bioorg Med Chem. 2013;21:632-42 pubmed publisher
    ..These promising results indicate that these tertiary diarylamine derivatives represent a novel class of tubulin polymerization inhibitors targeting the colchicine binding site and showing significant anti-proliferative activity. ..
  2. Calligaris D, Verdier Pinard P, Devred F, Villard C, Braguer D, Lafitte D. Microtubule targeting agents: from biophysics to proteomics. Cell Mol Life Sci. 2010;67:1089-104 pubmed publisher
    ..This will facilitate the design of improved and/or alternative chemotherapies targeting the microtubule cytoskeleton. ..
  3. Kavallaris M. Microtubules and resistance to tubulin-binding agents. Nat Rev Cancer. 2010;10:194-204 pubmed publisher
    ..Understanding the molecular mechanisms that mediate resistance to tubulin-binding agents will be vital to improve the efficacy of these agents. ..
  4. Quinones G, Danowski B, Devaraj A, Singh V, Ligon L. The posttranslational modification of tubulin undergoes a switch from detyrosination to acetylation as epithelial cells become polarized. Mol Biol Cell. 2011;22:1045-57 pubmed publisher
    ..However, in both 2D polarized and 3D polarized cells, the modified microtubules are oriented to support vectorial cargo transport to areas of high need. ..
  5. Fogh S, Machtay M, Werner Wasik M, Curran W, Bonanni R, Axelrod R, et al. Phase I trial using patupilone (epothilone B) and concurrent radiotherapy for central nervous system malignancies. Int J Radiat Oncol Biol Phys. 2010;77:1009-16 pubmed publisher
    ..Combined with a variety of radiation doses and fractionation schedules, concurrent patupilone was well tolerated and safe, with a maximal tolerated dose of 8 mg/m(2) every 3 weeks. ..
  6. Terrano D, Upreti M, Chambers T. Cyclin-dependent kinase 1-mediated Bcl-xL/Bcl-2 phosphorylation acts as a functional link coupling mitotic arrest and apoptosis. Mol Cell Biol. 2010;30:640-56 pubmed publisher
    ..Thus, phosphorylation of antiapoptotic Bcl-2 proteins acts as a sensor for CDK1 signal duration and as a functional link coupling mitotic arrest to apoptosis. ..
  7. Rathinasamy K, Jindal B, Asthana J, Singh P, Balaji P, Panda D. Griseofulvin stabilizes microtubule dynamics, activates p53 and inhibits the proliferation of MCF-7 cells synergistically with vinblastine. BMC Cancer. 2010;10:213 pubmed publisher
    ..The results revealed the antimitotic mechanism of action of griseofulvin and provided evidence suggesting that griseofulvin alone and/or in combination with vinblastine may have promising role in breast cancer chemotherapy. ..
  8. Yang H, Ganguly A, Cabral F. Inhibition of cell migration and cell division correlates with distinct effects of microtubule inhibiting drugs. J Biol Chem. 2010;285:32242-50 pubmed publisher
    ..We conclude that drugs produce differential dose-dependent effects at microtubule plus and minus-ends to inhibit different microtubule-mediated functions. ..
  9. Khrapunovich Baine M, Menon V, Yang C, Northcote P, Miller J, Angeletti R, et al. Hallmarks of molecular action of microtubule stabilizing agents: effects of epothilone B, ixabepilone, peloruside A, and laulimalide on microtubule conformation. J Biol Chem. 2011;286:11765-78 pubmed publisher
  10. Li C, Lu Y, Ahn S, Narayanan R, Miller D, Dalton J. Competitive mass spectrometry binding assay for characterization of three binding sites of tubulin. J Mass Spectrom. 2010;45:1160-6 pubmed publisher
    ..This new non-radioligand binding method to determine the binding site on tubulin will function as a useful tool to study the binding sites of tubulin inhibitors. ..
  11. Rohrer Bley C, Orlowski K, Furmanova P, McSheehy P, Pruschy M. Regulation of VEGF-expression by patupilone and ionizing radiation in lung adenocarcinoma cells. Lung Cancer. 2011;73:294-301 pubmed publisher
    ..These results demonstrate that patupilone and ionizing radiation dysregulate hypoxia-induced stress responses, which might contribute to the potency of this promising, combined treatment modality. ..
  12. Sengottuvel V, Leibinger M, Pfreimer M, Andreadaki A, Fischer D. Taxol facilitates axon regeneration in the mature CNS. J Neurosci. 2011;31:2688-99 pubmed publisher
  13. Yang H, Ganguly A, Yin S, Cabral F. Megakaryocyte lineage-specific class VI ?-tubulin suppresses microtubule dynamics, fragments microtubules, and blocks cell division. Cytoskeleton (Hoboken). 2011;68:175-87 pubmed publisher
    ..The results indicate that many of the morphological features of megakaryocyte differentiation can be recapitulated in non-hematopoietic cells by ?6 expression and they provide a mechanistic basis for understanding these changes. ..
  14. Guagliumi G, Costa M, Sirbu V, Musumeci G, Bezerra H, Suzuki N, et al. Strut coverage and late malapposition with paclitaxel-eluting stents compared with bare metal stents in acute myocardial infarction: optical coherence tomography substudy of the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardi. Circulation. 2011;123:274-81 pubmed publisher
    ..Further studies are required to determine the clinical significance of these findings. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00433966. ..
  15. Yoder A, Guo J, Yu D, Cui Z, Zhang X, Wu Y. Effects of microtubule modulators on HIV-1 infection of transformed and resting CD4 T cells. J Virol. 2011;85:3020-4 pubmed publisher
    ..Although these drugs disrupted microtubule integrity, almost no inhibition of HIV-1 infection was observed. Our results do not appear to support an essential role for microtubules in the initiation of HIV infection of CD4 T cells. ..
  16. Chatterji B, Jindal B, Srivastava S, Panda D. Microtubules as antifungal and antiparasitic drug targets. Expert Opin Ther Pat. 2011;21:167-86 pubmed publisher
  17. Ganguly A, Yang H, Cabral F. Paclitaxel-dependent cell lines reveal a novel drug activity. Mol Cancer Ther. 2010;9:2914-23 pubmed publisher
    ..We conclude that paclitaxel rescues mutant cell division by inhibiting the detachment of microtubule minus ends from centrosomes rather than by altering plus-end microtubule dynamics. ..
  18. Brunden K, Zhang B, Carroll J, Yao Y, Potuzak J, Hogan A, et al. Epothilone D improves microtubule density, axonal integrity, and cognition in a transgenic mouse model of tauopathy. J Neurosci. 2010;30:13861-6 pubmed publisher
    ..These results suggest that certain brain-penetrant MT-stabilizing agents might provide a viable therapeutic strategy for the treatment of AD and FTDs...
  19. Hammond J, Huang C, Kaech S, Jacobson C, Banker G, Verhey K. Posttranslational modifications of tubulin and the polarized transport of kinesin-1 in neurons. Mol Biol Cell. 2010;21:572-83 pubmed publisher
  20. Cortes J, Vidal M. Beyond taxanes: the next generation of microtubule-targeting agents. Breast Cancer Res Treat. 2012;133:821-30 pubmed publisher
    ..The development of new microtubule-targeting agents helps to address the need for additional effective regimens for patients progressing after standard treatment with anthracycline- and taxane-containing regimens. ..
  21. Chu S, Badar S, Morris D, Pourgholami M. Potent inhibition of tubulin polymerisation and proliferation of paclitaxel-resistant 1A9PTX22 human ovarian cancer cells by albendazole. Anticancer Res. 2009;29:3791-6 pubmed
    ..Data from this study suggest that ABZ is effective in suppressing growth of PTX-resistant ovarian tumour cells. ..
  22. Hayashi S, Yamamoto A, You F, Yamashita K, Ikegame Y, Tawada M, et al. The stent-eluting drugs sirolimus and paclitaxel suppress healing of the endothelium by induction of autophagy. Am J Pathol. 2009;175:2226-34 pubmed publisher
    ..These results suggest that phenotypic alteration in the endothelium by sirolimus or paclitaxel might affect the rates of late stent thrombosis, myocardial infarction, and mortality. ..
  23. Yang Z, Kenny A, Brito D, Rieder C. Cells satisfy the mitotic checkpoint in Taxol, and do so faster in concentrations that stabilize syntelic attachments. J Cell Biol. 2009;186:675-84 pubmed publisher
    ..They also offer an explanation for why some cells are more sensitive to lower versus higher Taxol concentrations. ..
  24. Bhattacharyya B, Kapoor S, Panda D. Fluorescence spectroscopic methods to analyze drug-tubulin interactions. Methods Cell Biol. 2010;95:301-29 pubmed publisher
    ..This will also help in developing molecules that have higher binding affinity to tubulin and can serve as potent anticancer agents. ..
  25. Von Dassow G, Verbrugghe K, Miller A, Sider J, Bement W. Action at a distance during cytokinesis. J Cell Biol. 2009;187:831-45 pubmed publisher
    ..We conclude that the asters confer accuracy and precision to a primary furrow-inducing signal that can reach the cell surface from the spindle without transport on microtubules...
  26. Gan P, McCarroll J, Po uha S, Kamath K, Jordan M, Kavallaris M. Microtubule dynamics, mitotic arrest, and apoptosis: drug-induced differential effects of betaIII-tubulin. Mol Cancer Ther. 2010;9:1339-48 pubmed publisher
  27. Nien C, Chen Y, Kuo C, Hsieh H, Chang C, Wu J, et al. 5-Amino-2-aroylquinolines as highly potent tubulin polymerization inhibitors. J Med Chem. 2010;53:2309-13 pubmed publisher
    ..Compound 15 (IC(50) = 1.6 microM) exhibited more potent inhibition of tubulin polymerization than 1a (IC(50) = 2.1 microM) and showed strong binding property to the colchicine binding site of microtubules. ..
  28. Zhang D, Sun L, Xian W, Liu F, Ling G, Xiao L, et al. Low-dose paclitaxel ameliorates renal fibrosis in rat UUO model by inhibition of TGF-beta/Smad activity. Lab Invest. 2010;90:436-47 pubmed publisher
    ..These data indicate that the low-dose paclitaxel ameliorates renal tubulointerstitial fibrosis by modulating TGF-beta signaling, and thus, the paclitaxel may have some therapeutic value in humans...
  29. Stengel C, Newman S, Leese M, Potter B, Reed M, Purohit A. Class III beta-tubulin expression and in vitro resistance to microtubule targeting agents. Br J Cancer. 2010;102:316-24 pubmed publisher
    ..Therefore, this study highlights for the first time the potential key role of targeting the colchicine-binding site, to develop new treatment modalities for taxane-refractory breast cancer. ..
  30. Perez E. Microtubule inhibitors: Differentiating tubulin-inhibiting agents based on mechanisms of action, clinical activity, and resistance. Mol Cancer Ther. 2009;8:2086-95 pubmed publisher
    ..This review will focus on the different mechanisms of action of MTIs, potential factors related to resistance and tolerability, and will discuss the recent approval as well as the development of new antineoplastic agents. ..
  31. Hirai S, Banba Y, Satake T, Ohno S. Axon formation in neocortical neurons depends on stage-specific regulation of microtubule stability by the dual leucine zipper kinase-c-Jun N-terminal kinase pathway. J Neurosci. 2011;31:6468-80 pubmed publisher
    ..Together, these in vivo and in vitro observations indicate that the DLK-JNK pathway facilitates axon formation in neocortical neurons via stage-specific regulation of microtubule stability. ..
  32. De Geest K, Blessing J, Morris R, Yamada S, Monk B, Zweizig S, et al. Phase II clinical trial of ixabepilone in patients with recurrent or persistent platinum- and taxane-resistant ovarian or primary peritoneal cancer: a gynecologic oncology group study. J Clin Oncol. 2010;28:149-53 pubmed publisher
  33. Hortobagyi G, Gomez H, Li R, Chung H, Fein L, Chan V, et al. Analysis of overall survival from a phase III study of ixabepilone plus capecitabine versus capecitabine in patients with MBC resistant to anthracyclines and taxanes. Breast Cancer Res Treat. 2010;122:409-18 pubmed publisher
    ..The observed differences in survival favored the combination arm. A clinical benefit was also seen in patients in the KPS 70-80 subgroup. ..
  34. Bounoutas A, O HAGAN R, Chalfie M. The multipurpose 15-protofilament microtubules in C. elegans have specific roles in mechanosensation. Curr Biol. 2009;19:1362-7 pubmed publisher
    ..Touching e1605 animals produces a reduced mechanoreceptor current that inactivates more rapidly than in wild-type, suggesting a specific role of the microtubules in mechanotransduction. ..
  35. Barlis P, Regar E, Serruys P, Dimopoulos K, van der Giessen W, van Geuns R, et al. An optical coherence tomography study of a biodegradable vs. durable polymer-coated limus-eluting stent: a LEADERS trial sub-study. Eur Heart J. 2010;31:165-76 pubmed publisher
    ..The impact of this difference on clinical outcome and, in particular, on the risk of late stent thrombosis is yet to be determined. ..
  36. White E. Mechanical modulation of cardiac microtubules. Pflugers Arch. 2011;462:177-84 pubmed publisher
    ..Microtubules certainly play a role in the response of cardiac myocytes to mechanical stimulation, the exact nature and significance of this role is still to be fully determined. ..
  37. Jeong K, Kwon H, Lee J, Jang D, Hwang E, Park J, et al. Rab6-mediated retrograde transport regulates inner nuclear membrane targeting of caveolin-2 in response to insulin. Traffic. 2012;13:1218-33 pubmed publisher
  38. Ma Y, Fang S, Li H, Han C, Lu Y, Zhao Y, et al. Biological evaluation and molecular modelling study of podophyllotoxin derivatives as potent inhibitors of tubulin polymerization. Chem Biol Drug Des. 2013;82:12-21 pubmed publisher
    ..Our results helped us understand the nature of tubulin binding and determine the core design of a new series of potent inhibitors of tubulin polymerization. ..
  39. Peltan A, Briggs L, Matthews G, Sweeney S, Smith D. Identification of Drosophila gene products required for phagocytosis of Leishmania donovani. PLoS ONE. 2012;7:e51831 pubmed publisher
    ..These observations suggest that this experimental approach has the potential to identify a large number of host effectors required for efficient parasite uptake and maintenance. ..
  40. Bajwah S, Ross J, Peacock J, Higginson I, Wells A, Patel A, et al. Interventions to improve symptoms and quality of life of patients with fibrotic interstitial lung disease: a systematic review of the literature. Thorax. 2013;68:867-79 pubmed publisher
    ..Future recommendations for research would include careful consideration of the dichotomy of radical and palliative treatments when deciding on how symptom and QoL outcome measures are used and data presented. ..
  41. Aziz J, Brachet E, Hamze A, Peyrat J, Bernadat G, Morvan E, et al. Synthesis, biological evaluation, and structure-activity relationships of tri- and tetrasubstituted olefins related to isocombretastatin A-4 as new tubulin inhibitors. Org Biomol Chem. 2013;11:430-42 pubmed publisher
    ..Docking studies in the colchicine binding site of tubulin allowed identification of residues most likely to interact with these inhibitors and explain their potent anti-tubulin activity. ..
  42. Chakraborti S, Chakravarty D, Gupta S, Chatterji B, Dhar G, Poddar A, et al. Discrimination of ligands with different flexibilities resulting from the plasticity of the binding site in tubulin. Biochemistry. 2012;51:7138-48 pubmed
    ..This analysis provides lessons for the design of new ligands that should balance between the "better fit" and "flexibility"', instead of focusing only on the receptor-ligand interactions. ..
  43. Entwistle R, Rizk R, Cheng D, Lushington G, Himes R, Gupta M. Differentiating between models of epothilone binding to microtubules using tubulin mutagenesis, cytotoxicity, and molecular modeling. ChemMedChem. 2012;7:1580-6 pubmed publisher
    ..This work establishes a system for discriminating between potential binding modes and among various compounds and/or analogues using a sensitive biological activity-based readout. ..
  44. Cartelli D, Casagrande F, Busceti C, Bucci D, Molinaro G, Traficante A, et al. Microtubule alterations occur early in experimental parkinsonism and the microtubule stabilizer epothilone D is neuroprotective. Sci Rep. 2013;3:1837 pubmed publisher
    ..These data suggest that alteration of ??s is an early event specifically associated with dopaminergic neuron degeneration. Pharmacological stabilization of MTs may be a viable strategy for the management of parkinsonism. ..
  45. Wang G, Song L, Wang H, Xing N. Quercetin synergizes with 2-methoxyestradiol inhibiting cell growth and inducing apoptosis in human prostate cancer cells. Oncol Rep. 2013;30:357-63 pubmed publisher
    ..The combination of quercetin and 2-ME is a new clinically relevant treatment regimen which has the potential of enhancing the antitumor effect on prostate cancer and lessening the side effect of either quercetin or 2-ME alone. ..
  46. Pirnik Z, Bundzikova J, Kiss A. High fat diet impact on Fos expression in ovariectomized female C57BL/6 mice: effect of colchicine and response of different neuronal phenotypes. Endocr Regul. 2012;46:91-7 pubmed
  47. van de Ree Pellikaan C, Kiewiet Kemper R, Tchetverikov I, Westerweel P. Oral ulcerations after placement of orthodontic braces and skin pustules after laser hair removal: novel inducers of pathergy reactions in new-onset Behçet's disease. BMJ Case Rep. 2016;2016: pubmed publisher
    ..Treatment with colchicine and prednisone resulted in rapid improvement of his symptoms. Pathergy reactions in response to placement of dental braces and laser hair removal are a rare first presentation of Behçet's disease. ..
  48. Lukesh J, Carney D, Dong H, Cross R, Shukla V, Duncan K, et al. Vinblastine 20' Amides: Synthetic Analogues That Maintain or Improve Potency and Simultaneously Overcome Pgp-Derived Efflux and Resistance. J Med Chem. 2017;60:7591-7604 pubmed publisher
  49. Liu J, Shimizu K, Tanaka A, Shinobu W, Ohnuki K, Nakamura T, et al. Target proteins of ganoderic acid DM provides clues to various pharmacological mechanisms. Sci Rep. 2012;2:905 pubmed publisher
    ..This study revealed multiple biological activities of 1 and may contribute to the design and development of new tubulin-inhibiting agents. ..
  50. Abuhaie C, Bîcu E, Rigo B, Gautret P, Belei D, Farce A, et al. Synthesis and anticancer activity of analogues of phenstatin, with a phenothiazine A-ring, as a new class of microtubule-targeting agents. Bioorg Med Chem Lett. 2013;23:147-52 pubmed publisher
    ..The same compound showed a better inhibition of COLO 205, A498, and MCF7 cell lines than the parent phenstatin. ..
  51. Zhang H, Liu J, Sun J, Yang X, Zhao T, Lu X, et al. Design, synthesis and biological evaluation of novel chalcone derivatives as antitubulin agents. Bioorg Med Chem. 2012;20:3212-8 pubmed publisher
    ..Based on the preliminary results, compound 3d with potent inhibitory activity in tumor growth may be a potential anticancer agent. ..
  52. Langelueddecke C, Lee W, Thevenod F. Differential transcytosis and toxicity of the hNGAL receptor ligands cadmium-metallothionein and cadmium-phytochelatin in colon-like Caco-2 cells: implications for in vivo cadmium toxicity. Toxicol Lett. 2014;226:228-35 pubmed publisher
  53. Lysko D, Putt M, Golden J. SDF1 reduces interneuron leading process branching through dual regulation of actin and microtubules. J Neurosci. 2014;34:4941-62 pubmed publisher