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Tubacin

Tubacin is a highly potent and selective, reversible, cell-permeable HDAC6 inhibitor with an IC50 of 4 nM. The IC50 for other HDACs is 1000-fold higher, making tubacin both more selective and more potent than Tubastatin A, which also inhibits HDAC8. Tubacin inhibits alpha-tubulin deacetylation in mammalian cells. Unlike trichostatin A (TSA), which is a broad spectrum HDAC inhibitor, tubacin is specific for the tubulin deacetylase activity of HDAC6. Tubacin is a synthetic small molecule with chemical formula C41H43N3O7S and molecular weight: 721.86. It's chemical name is N1-(4-((2R,4R,6S)-4-(((4,5-diphenyloxazol-2-yl)thio)methyl)-6-(4-(hydroxymethyl)phenyl)-1,3-dioxan-2-yl)phenyl)-N8-hydroxyoctanediamide.  The total synthesis of tubacin was described by Hong et al [Letters in Organic Chemistry (2010), 7(1), 50-53].

Current developer:   Dana-Farber and The Broad Institute

Tubacin was originally discovered by scientists at the Broad Institute after performing a cell-based screen of a library of over 7000 small molecules. Tubacin is a highly potent, selective, reversible, cell-permeable HDAC6 inhibitor with an IC50 of 4 nM. The IC50 for other HDACs is 1000-fold higher, making tubacin both more selective and more potent than Tubastatin A.

According to Aldana-Masangkay et al's recent publication (Leuk Lymphoma. 2011 Aug;52(8):1544-55.)  tubacin showed a higher antiproliferative effect in acute lymphoblastic leukemia (ALL) cells than in normal hematopoietic cells. Treatment with tubacin led to the induction of apoptotic pathways in both pre-B and T cell ALL cells at a 50% inhibitory concentration (IC(50)) of low micromolar concentrations. Acetylation of α-tubulin increases within the first 30 min following treatment of ALL cells with tubacin. It was also observed an accumulation of polyubiquitinated proteins and poly(ADP-ribose) polymerase (PARP) cleavage. Furthermore, the signaling pathways activated by tubacin appear to be distinct from those observed in multiple myeloma. The results suggest that targeting HDAC6 alone or in combination with chemotherapy could provide a novel approach to treat ALL.

1: Aldana-Masangkay GI, Rodriguez-Gonzalez A, Lin T, Ikeda AK, Hsieh YT, Kim YM, Lomenick B, Okemoto K, Landaw EM, Wang D, Mazitschek R, Bradner JE, Sakamoto KM. Tubacin suppresses proliferation and induces apoptosis of acute lymphoblastic leukemia cells. Leuk Lymphoma. 2011 Aug;52(8):1544-55. Epub 2011 Jun 23. PubMed PMID: 21699378.

2: Kawada J, Zou P, Mazitschek R, Bradner JE, Cohen JI. Tubacin kills Epstein-Barr virus (EBV)-Burkitt lymphoma cells by inducing reactive oxygen species and EBV lymphoblastoid cells by inducing apoptosis. J Biol Chem. 2009 Jun 19;284(25):17102-9. Epub 2009 Apr 22. PubMed PMID: 19386607; PubMed Central PMCID: PMC2719348.

3. Particles for multiple drug delivery By Farokhzad, Omid C.; Kolishetti, Nagesh; Dhar, Shanta; Lippard, Stephen J.; Langer, Robert S. From PCT Int. Appl. (2011), WO 2011084620 A2 20110714.

4. p21Cip1 regulates cell-substrate adhesion and interphase microtubule dynamics in untransformed human mammary epithelial cells By Bouchet, Benjamin Pierre; Fauvet, Frederique; Grelier, Gael; Galmarini, Carlos Maria; Puisieux, Alain From European Journal of Cell Biology (2011), 90(8), 631-641.

5. Pharmacological inhibition of HDAC6 attenuates endothelial barrier dysfunction induced by thrombin By Saito, Shigeki; Lasky, Joseph A.; Guo, Weichao; Nguyen, Hong; Mai, Antonello; Danchuk, Svitlana; Sullivan, Deborah E.; Shan, Bin From Biochemical and Biophysical Research Communications (2011), 408(4), 630-634.

6. Suberoylanilide Hydroxamic Acid (Vorinostat) Up-regulates Progranulin Transcription: Rational therapeutic approach to frontotemporal dementia By Cenik, Basar; Sephton, Chantelle F.; Dewey, Colleen M.; Xian, Xun-De; Wei, Shu-Guang; Yu, Kimberley; Niu, Wen-Ze; Coppola, Giovanni; Coughlin, Sarah E.; Lee, Suzee E.; et al From Journal of Biological Chemistry (2011), 286(18), 16101-16108.

7. Microtubule-associated deacetylase HDAC6 promotes angiogenesis by regulating cell migration in an EB1-dependent manner By Li, Dengwen; Xie, Songbo; Ren, Yuan; Huo, Lihong; Gao, Jinmin; Cui, Dandan; Liu, Min; Zhou, Jun From Protein & Cell (2011), 2(2), 150-160.

8. Class- and isoform-specific HDAC inhibitors and uses thereof By Mazitschek, Ralph; Bradner, James Elliot From PCT Int. Appl. (2011), WO 2011019393 A2 20110217.

9. HDAC 6 inhibitor-based methods for treating cancer By Marks, Paul A.; Namdar, Mandana; Xu, Weisheng From PCT Int. Appl. (2011), WO 2011005688 A1 20110113.

10. Vorinostat synergises with capecitabine through upregulation of thymidine phosphorylase By Di Gennaro, E.; Piro, G.; Chianese, M. I.; Franco, R.; Di Cintio, A.; Moccia, T.; Luciano, A.; de Ruggiero, I.; Bruzzese, F.; Avallone, A.; et al From British Journal of Cancer (2010), 103(11), 1680-1691.

11. Selective inhibition of histone deacetylase 6 (HDAC6) induces DNA damage and sensitizes transformed cells to anticancer agents By Namdar, Mandana; Perez, Gisela; Ngo, Lang; Marks, Paul A. From Proceedings of the National Academy of Sciences of the United States of America (2010), 107(46), 20003-20008, S20003/1-S20003/4.

12. Selective inhibition of histone deacetylase 6 (HDAC6) induces DNA damage and sensitizes transformed cells to anticancer agents By Namdar, Mandana; Perez, Gisela; Ngo, Lang; Marks, Paul A. From Proceedings of the National Academy of Sciences of the United States of America, Early Edition (2010), (Oct 29 2010), 1-6, 6 pp..

13. Impaired function of HDAC6 slows down axonal growth and interferes with axon initial segment development By Tapia, Monica; Wandosell, Francisco; Garrido, Juan Jose From PLoS One (2010), 5(9), No pp. given.

14. ER sliding dynamics and ER-mitochondrial contacts occur on acetylated microtubules By Friedman, Jonathan R.; Webster, Brant M.; Mastronarde, David N.; Verhey, Kristen J.; Voeltz, Gia K. From Journal of Cell Biology (2010), 190(3), 363-375.

15. Histone/protein deacetylase inhibitors increase suppressive functions of human FOXP3+ Tregs By Akimova, Tatiana; Ge, Guanghui; Golovina, Tatiana; Mikheeva, Tatiana; Wang, Liqing; Riley, James L.; Hancock, Wayne W. From Clinical Immunology (Amsterdam, Netherlands) (2010), 136(3), 348-363.

16. Rational Design and Simple Chemistry Yield a Superior, Neuroprotective HDAC6 Inhibitor, Tubastatin A By Butler, Kyle V.; Kalin, Jay; Brochier, Camille; Vistoli, Guilio; Langley, Brett; Kozikowski, Alan P. From Journal of the American Chemical Society (2010), 132(31), 10842-10846.

17. Method for killing tumor by photosensitization treatment under conditions where histone is highly acetylated By Toyooka, Tatsushi; Ibuki, Yuko From PCT Int. Appl. (2010), WO 2010064422 A1 20100610.

18. HDAC6 regulates mitochondrial transport in hippocampal neurons By Chen, Sigeng; Owens, Geoffrey C.; Makarenkova, Helen; Edelman, David B. From PLoS One (2010), 5(5), No pp. given.

19. Compositions and methods for the treatment of diseases associated with aberrant cilia assembly and regulation By Plotnikova, Olga V.; Pugacheva, Elena N.; Golemis, Erica A. From U.S. Pat. Appl. Publ. (2010), US 20100137409 A1 20100603.

20. Selective inhibition of histone deacetylase 6 for ocular neuroprotection or for treatment or control of glaucoma By Bartels, Stephen P. From U.S. Pat. Appl. Publ. (2010), US 20100136024 A1 20100603.

21. On the inhibition of histone deacetylase 8 By Estiu, Guillermina; West, Nathan; Mazitschek, Ralph; Greenberg, Edward; Bradner, James E.; Wiest, Olaf From Bioorganic & Medicinal Chemistry (2010), 18(11), 4103-4110.

22. The influence of mediators of intracellular trafficking on transgene expression efficacy of polymer-plasmid DNA complexes By Barua, Sutapa; Rege, Kaushal From Biomaterials (2010), 31(22), 5894-5902.

23. Methods of inhibiting cancer cell growth with HDAC inhibitors and methods of screening for HDAC10 inhibitors By Yao, Tso-Pang; Sasajima, Hitoshi; Kawaguchi, Yoshiharu; Cui, Kai; Lai, Chun-Hsiang From PCT Int. Appl. (2010), WO 2010056677 A1 20100520.

24. A new approach to tubacin By Hong, Jian; Xu, Xin; Das, Debasis; Yang, Pengyu; Chen, Shu-Hui; Li, Ge From Letters in Organic Chemistry (2010), 7(1), 50-53.

25. Chemical phylogenetics of histone deacetylases By Bradner, James E.; West, Nathan; Grachan, Melissa L.; Greenberg, Edward F.; Haggarty, Stephen J.; Warnow, Tandy; Mazitschek, Ralph From Nature Chemical Biology (2010), 6(3), 238-243.

26. Use of histone acetylation-promoting compounds for the treatment of cancers characterized by chromosomal rearrangement of the NUT gene By French, Christopher; Aster, Jon; Hofer, Matthias; Bradner, James From PCT Int. Appl. (2010), WO 2010011700 A2 20100128.

27. Deacetylase inhibitors for proliferative diseases therapy By Tang, Weiping; Bradner, James Elliot; Schreiber, Stuart L. From PCT Int. Appl. (2010), WO 2010011296 A2 20100128.

28. Regulation of microtubule dynamics by inhibition of the tubulin deacetylase HDAC6 By Zilberman, Yuliya; Ballestrem, Christoph; Carramusa, Letizia; Mazitschek, Ralph; Khochbin, Saadi; Bershadsky, Alexander From Journal of Cell Science (2009), 122(19), 3531-3541.

29. Tubacin Kills Epstein-Barr Virus (EBV)-Burkitt Lymphoma Cells by Inducing Reactive Oxygen Species and EBV Lymphoblastoid Cells by Inducing Apoptosis By Kawada, Junichi; Zou, Ping; Mazitschek, Ralph; Bradner, James E.; Cohen, Jeffrey I. From Journal of Biological Chemistry (2009), 284(25), 17102-17109.

30. HDAC6 Modulates Hsp90 Chaperone Activity and Regulates Activation of Aryl Hydrocarbon Receptor Signaling By Kekatpure, Vikram D.; Dannenberg, Andrew J.; Subbaramaiah, Kotha From Journal of Biological Chemistry (2009), 284(12), 7436-7445.

31. HDAC inhibition upregulates the expression of angiostatic ADAMTS1. [Erratum to document cited in CA150:159578] By Chou, Chia-Wei; Chen, Ching-Chow From FEBS Letters (2009), 583(3), 596.

32. Methods and compositions for regulating histone deacetylase 4 (HDAC4) activity, and use of HDAC4 inhibitors for the treatment of muscle atrophy and/or inflammation By Yao, Tso-Pang; Cohen, Todd; Barrientos de Renshaw, Tomasa From U.S. Pat. Appl. Publ. (2008), US 20080312175 A1 20081218.

33. HDAC inhibition upregulates the expression of angiostatic ADAMTS1 By Chou, Chia-Wei; Chen, Ching-Chow From FEBS Letters (2008), 582(29), 4059-4065.

34. Ghrelin modulating compounds and combinations thereof By Watson, Alan; Distefano, Peter; Geesaman, Bard J. From PCT Int. Appl. (2008), WO 2008141189 A1 20081120.

35. Ubiquitin Proteasome System Stress Underlies Synergistic Killing of Ovarian Cancer Cells by Bortezomib and a Novel HDAC6 Inhibitor By Bazzaro, Martina; Lin, Zhenhua; Santillan, Antonio; Lee, Michael K.; Wang, Mei-Cheng; Chan, Kwun C.; Bristow, Robert E.; Mazitschek, Ralph; Bradner, James; Roden, Richard B. S. From Clinical Cancer Research (2008), 14(22), 7340-7347.

36. Preparation of salinosporamide A and analogous [3.2.0] bicyclic β-lactones for therapeutic use as proteasome inhibitors in combination with histone deacetylase inhibitors in the treatment of cancer By Palladino, Michael; Anderson, Kenneth C.; Chauhan, Dharminder; Chandra, Joya; Mcconkey, David From PCT Int. Appl. (2008), WO 2008124699 A1 20081016.

37. Histone deacetylase 6 interacts with the microtubule-associated protein tau By Ding, Huiping; Dolan, Philip J.; Johnson, Gail V. W. From Journal of Neurochemistry (2008), 106(5), 2119-2130.

38. HDAC6 inhibition enhances 17-AAG-mediated abrogation of hsp90 chaperone function in human leukemia cells By Rao, Rekha; Fiskus, Warren; Yang, Yonghua; Lee, Pearl; Joshi, Rajeshree; Fernandez, Pravina; Mandawat, Aditya; Atadja, Peter; Bradner, James E.; Bhalla, Kapil From Blood (2008), 112(5), 1886-1893.

39. Methods and compositions using histone deacetylase inhibitors for inhibition of excessive weight gain, reduction of inappropriate eating behaviors and inhibition of binge eating for the treatment of obesity By Regan, Claran M.; Foley, Andrew G. From PCT Int. Appl. (2008), WO 2008090534 A1 20080731.

40. Requirement of HDAC6 for transforming growth factor-β1-induced epithelial-mesenchymal transition By Shan, Bin; Yao, Tso-pang; Nguyen, Hong T.; Zhuo, Ying; Levy, Dawn R.; Klingsberg, Ross C.; Tao, Hui; Palmer, Michael L.; Holder, Kevin N.; Lasky, Joseph A. From Journal of Biological Chemistry (2008), 283(30), 21065-21073.

41. The aggresome pathway as a target for therapy in hematologic malignancies By Simms-Waldrip, Tiffany; Rodriguez-Gonzalez, Agustin; Lin, Tara; Ikeda, Alan K.; Fu, Cecilia; Sakamoto, Kathleen M. From Molecular Genetics and Metabolism (2008), 94(3), 283-286.

42. Structural Origin of Selectivity in Class II-Selective Histone Deacetylase Inhibitors By Estiu, Guillermina; Greenberg, Edward; Harrison, Christopher B.; Kwiatkowski, Nicholas P.; Mazitschek, Ralph; Bradner, James E.; Wiest, Olaf From Journal of Medicinal Chemistry (2008), 51(10), 2898-2906.

43. Compositions and methods for the treatment of diseases associated with aberrant cilia assembly and regulation By Golemis, Erica A.; Pugacheva, Elena A. From PCT Int. Appl. (2008), WO 2008011430 A2 20080124.

44. Solid oral dosage form containing deacetylase inhibitor and an enhancer By Leonard, Thomas W.; O'Toole, Edel; Feeney, Orlagh From U.S. Pat. Appl. Publ. (2007), US 20070292512 A1 20071220.

45. Isotubacin and isoisotubacin compound histone deacetylase and tubulin deacetylase inhibitors and aggresome inhibitors, and their therapeutic use By Mazitschek, Ralph; Kwiatkowski, Nicholas Paul; Bradner, James Elliott From PCT Int. Appl. (2007), WO 2007130429 A2 20071115.

46. The "Epigenetic Code Replication Machinery", ECREM: a promising drugable target of the epigenetic cell memory By Bronner, Christian; Chataigneau, Thierry; Schini-Kerth, Valerie B.; Landry, Yves From Current Medicinal Chemistry (2007), 14(25), 2629-2641.

47. Design, synthesis, structure-selectivity relationship, and effect on human cancer cells of a novel series of histone deacetylase 6-selective inhibitors By Itoh, Yukihiro; Suzuki, Takayoshi; Kouketsu, Akiyasu; Suzuki, Nobuaki; Maeda, Satoko; Yoshida, Minoru; Nakagawa, Hidehiko; Miyata, Naoki From Journal of Medicinal Chemistry (2007), 50(22), 5425-5438.

48. Methods and compositions for regulating HDAC6 activity By Yao, Tso-Pang; Kovacs, Jeffrey J.; Hubbert, Charlotte; Lee, Yi-Shan; Gao, Ya-Sheng; Wu, June-Tai From U.S. Pat. Appl. Publ. (2007), US 20070207950 A1 20070906.

49. Controlled release solid oral dosage form containing a histone deacetylase inhibitor and a medium chain fatty acid derivative as an absorption enhancer By Cumming, Kenneth I.; Ramtoola, Zebunnissa; Leonard, Thomas Waymond From U.S. Pat. Appl. Publ. (2007), US 20070148228 A1 20070628.

50. HDAC6 deacetylation of tubulin modulates dynamics of cellular adhesions By Tran, Andy Dong-Anh; Marmo, Timothy P.; Salam, Ambar A.; Che, Sally; Finkelstein, Erik; Kabarriti, Rafi; Xenias, Harry S.; Mazitschek, Ralph; Hubbert, Charlotte; Kawaguchi, Yoshiharu; et al From Journal of Cell Science (2007), 120(8), 1469-1479.

51. Design of class selective HDAC inhibitors By Estiu, Guillermina; Harrison, Chris; Wiest, Olaf; Mazitschek, Ralph; Bradner, James From Abstracts of Papers, 233rd ACS National Meeting, Chicago, IL, United States, March 25-29, 2007 (2007), MEDI-447.

52. Multicyclic sulfonamide compounds as inhibitors of histone deacetylase for the treatment of disease and their preparation By Malecha, James W.; Noble, Stewart A.; Wiley, Brandon M.; Hoffman, Timothy Z.; Bonnefous, Celine; Sertic, Michael; Wash, Paul L.; Smith, Nicholas D.; Hassig, Christian A.; Scranton, Shawn A.; et al From U.S. Pat. Appl. Publ. (2007), US 20070027184 A1 20070201.

53. Tubulin must be acetylated in order to form a complex with membrane Na+,K+-ATPase and to inhibit its enzyme activity By Santander, Veronica S.; Bisig, C. Gaston; Purro, Silvia A.; Casale, Cesar H.; Arce, Carlos A.; Barra, Hector S. From Molecular and Cellular Biochemistry (2006), 291(1&2), 167-174.

54. Treatment of protein degradation disorders By Anderson, Kenneth C.; Bradner, James Elliott; Greenberg, Edward Franklin; Hideshima, Teru; Kwiatkowski, Nicholas Paul; Mazitschek, Ralph; Schreiber, Stuart L.; Shaw, Jared From PCT Int. Appl. (2006), WO 2006102557 A2 20060928.

55. Lymphocyte chemotaxis is regulated by histone deacetylase 6, independently of its deacetylase activity By Cabrero, J. Roman; Serrador, Juan M.; Barreiro, Olga; Mittelbrunn, Maria; Naranjo-Suarez, Salvador; Martin-Cofreces, Noa; Vicente-Manzanares, Miguel; Mazitschek, Ralph; Bradner, James E.; Avila, Jesus; et al From Molecular Biology of the Cell (2006), 17(8), 3435-3445.

56. Method to treat bone disease by promoting bone formation activity of BMP by enhancing RUNX2 acetylation By Bae, Suk-Chul; Ryoo, Hyun-Mo From PCT Int. Appl. (2006), WO 2006065075 A1 20060622.

57. Substrate and inhibitor specificity of class 1 and class 2 histone deacetylases By Hildmann, Christian; Wegener, Dennis; Riester, Daniel; Hempel, Rene; Schober, Andreas; Merana, Joachim; Giurato, Laura; Guccione, Salvatore; Nielsen, Tine Kragh; Ficner, Ralf; et al From Journal of Biotechnology (2006), 124(1), 258-270.

58. Effect of histone deacetylase inhibitors on tubulin acetylation and development in Volvox carteri (Volvocales) By Cheng, Qian; Balzer, Eric; Miller, Stephen M.; Yoshida, Minoru; Wong, Jason C. From Journal of Phycology (2006), 42(2), 417-422.

59. Small-molecular inhibition of proteasome and aggresome function induces synergic antitumor activity in multiple myeloma By Hideshima, Teru From Jikken Igaku (2005), 23(16), 2475-2478.

60. Method for identifying HDAC6 tubulin deacetylase-modulating compounds and their use in treatment of immunological diseases By Serador Peiro, Juan Manuel; Cabrero Garcia, J. Roman; Sancho Madrid, David; Mittlebrunn Herrero, Maria; Urzainqui Mayayo, Ana; Sanchez Madrid, Francisco From PCT Int. Appl. (2005), WO 2005078081 A1 20050825.

61. Significance of HDAC6 regulation via estrogen signaling for cell motility and prognosis in estrogen receptor-positive breast cancer By Saji, Shigehira; Kawakami, Masayo; Hayashi, Shin-ichi; Yoshida, Nobuyuki; Hirose, Makiko; Horiguchi, Shin-ichiro; Itoh, Akihiro; Funata, Nobuaki; Schreiber, Stuart L.; Yoshida, Minoru; et al From Oncogene (2005), 24(28), 4531-4539.

62. Small-molecule inhibition of proteasome and aggresome function induces synergistic antitumor activity in multiple myeloma By Hideshima, Teru; Bradner, James E.; Wong, Jason; Chauhan, Dharminder; Richardson, Paul; Schreiber, Stuart L.; Anderson, Kenneth C. From Proceedings of the National Academy of Sciences of the United States of America (2005), 102(24), 8567-8572.

63. The synergistic combination of the farnesyl transferase inhibitor lonafarnib and paclitaxel enhances tubulin acetylation and requires a functional tubulin deacetylase By Marcus, Adam I.; Zhou, Jun; O'Brate, Aurora; Hamel, Ernest; Wong, Jason; Nivens, Michael; El-Naggar, Adel; Yao, Tso-Pang; Khuri, Fadlo R.; Giannakakou, Paraskevi From Cancer Research (2005), 65(9), 3883-3893.

64. Mapping chemical space using molecular descriptors and chemical genetics: Deacetylase inhibitors By Haggarty, Stephen J.; Clemons, Paul A.; Wong, Jason C.; Schreiber, Stuart L. From Combinatorial Chemistry and High Throughput Screening (2004), 7(7), 669-676.

65. Preparation of trisubstituted dioxanes as histone deacetylase inhibitors. By Schreiber, Stuart L.; Sternson, Scott M.; Wong, Jason C.; Grozinger, Christina M.; Haggarty, Stephen J.; Koeller, Kathryn M. From U.S. Pat. Appl. Publ. (2004), US 20040072849 A1 20040415.

66. Multidimensional Chemical Genetic Analysis of Diversity-Oriented Synthesis-Derived Deacetylase Inhibitors Using Cell-Based Assays By Haggarty, Stephen J.; Koeller, Kathryn M.; Wong, Jason C.; Butcher, Rebecca A.; Schreiber, Stuart L. From Chemistry & Biology (2003), 10(5), 383-396.

67. Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation By Haggarty, Stephen J.; Koeller, Kathryn M.; Wong, Jason C.; Grozinger, Christina M.; Schreiber, Stuart L. From Proceedings of the National Academy of Sciences of the United States of America (2003), 100(8), 4389-4394.

68. Structural Biasing Elements for In-Cell Histone Deacetylase Paralog Selectivity By Wong, Jason C.; Hong, Roger; Schreiber, Stuart L. From Journal of the American Chemical Society (2003), 125(19), 5586-5587.

69. Histone deacetylase 6 and heat shock protein 90 control the functions of Foxp3(+) T-regulatory cells By de Zoeten Edwin F; Wang Liqing; Butler Kyle; Beier Ulf H; Akimova Tatiana; Sai Hong; Bradner James E; Mazitschek Ralph; Kozikowski Alan P; Matthias Patrick; et al From Molecular and cellular biology (2011), 31(10), 2066-78.

70. Selective inhibition of histone deacetylase 6 (HDAC6) induces DNA damage and sensitizes transformed cells to anticancer agents By Namdar Mandana; Perez Gisela; Ngo Lang; Marks Paul A From Proceedings of the National Academy of Sciences of the United States of America (2010), 107(46), 20003-8.

71. Impaired function of HDAC6 slows down axonal growth and interferes with axon initial segment development By Tapia Monica; Wandosell Francisco; Garrido Juan Jose From PloS one (2010), 5(9), e12908.

72. HDAC6 regulates mitochondrial transport in hippocampal neurons By Chen Sigeng; Owens Geoffrey C; Makarenkova Helen; Edelman David B From PloS one (2010), 5(5), e10848.

73. Acetylation of microtubules influences their sensitivity to severing by katanin in neurons and fibroblasts By Sudo Haruka; Baas Peter W From The Journal of neuroscience : the official journal of the Society for Neuroscience (2010), 30(21), 7215-26.

74. Expansion of the trans-Golgi network following activated collagen secretion is supported by a coiled-coil microtubule-bundling protein, p180, on the ER By Ueno Tomonori; Kaneko Keiko; Katano Harutaka; Sato Yuko; Mazitschek Ralph; Tanaka Keisuke; Hattori Shunji; Irie Shinkichi; Sata Tetsutaro; Ogawa-Goto Kiyoko From Experimental cell research (2010), 316(3), 329-40.

75. The NIMA-family kinase Nek3 regulates microtubule acetylation in neurons By Chang Jufang; Baloh Robert H; Milbrandt Jeffrey From Journal of cell science (2009), 122(Pt 13), 2274-82.

76. Fold up or perish: unfolded protein response and chemotherapy By Strasser A; Puthalakath H From Cell death and differentiation (2008), 15(2), 223-5.