Tubulins are a family of intracellular proteins most commonly associated with microtubules, part of the cytoskeleton. They are exploited for therapeutic gain in cancer chemotherapy as targets for agents derived from a variety of natural products: taxanes, colchicine and vinca alkaloids. These are thought to act primarily through β-tubulin, thereby interfering with the normal processes of tubulin polymer formation and disassembly.

* Key recommended reading is highlighted with an asterisk

* Arnst KE, Banerjee S, Chen H, Deng S, Hwang DJ, Li W, Miller DD. (2019) Current advances of tubulin inhibitors as dual acting small molecules for cancer therapy. Med Res Rev, 39 (4): 1398-1426. [PMID:30746734]

Barisic M, Maiato H. (2016) The Tubulin Code: A Navigation System for Chromosomes during Mitosis. Trends Cell Biol, 26 (10): 766-775. [PMID:27344407]

Bates D, Eastman A. (2017) Microtubule destabilising agents: far more than just antimitotic anticancer drugs. Br J Clin Pharmacol, 83 (2): 255-268. [PMID:27620987]

* Boiarska Z, Passarella D. (2021) Microtubule-targeting agents and neurodegeneration. Drug Discov Today, 26 (2): 604-615. [PMID:33279455]

Borisy G, Heald R, Howard J, Janke C, Musacchio A, Nogales E. (2016) Microtubules: 50 years on from the discovery of tubulin. Nat Rev Mol Cell Biol, 17 (5): 322-8. [PMID:27103327]

* Eshun-Wilson L, Zhang R, Portran D, Nachury MV, Toso DB, Löhr T, Vendruscolo M, Bonomi M, Fraser JS, Nogales E. (2019) Effects of α-tubulin acetylation on microtubule structure and stability. Proc Natl Acad Sci USA, 116 (21): 10366-10371. [PMID:31072936]

Gadadhar S, Bodakuntla S, Natarajan K, Janke C. (2017) The tubulin code at a glance. J Cell Sci, 130 (8): 1347-1353. [PMID:28325758]

Kaur R, Kaur G, Gill RK, Soni R, Bariwal J. (2014) Recent developments in tubulin polymerization inhibitors: An overview. Eur J Med Chem, 87: 89-124. [PMID:25240869]

Lu Y, Chen J, Xiao M, Li W, Miller DD. (2012) An overview of tubulin inhibitors that interact with the colchicine binding site. Pharm Res, 29 (11): 2943-71. [PMID:22814904]

* Magiera MM, Singh P, Gadadhar S, Janke C. (2018) Tubulin Posttranslational Modifications and Emerging Links to Human Disease. Cell, 173 (6): 1323-1327. [PMID:29856952]

* Penna LS, Henriques JAP, Bonatto D. (2017) Anti-mitotic agents: Are they emerging molecules for cancer treatment?. Pharmacol Ther, 173: 67-82. [PMID:28174095]

Perdiz D, Mackeh R, Poüs C, Baillet A. (2011) The ins and outs of tubulin acetylation: more than just a post-translational modification?. Cell Signal, 23 (5): 763-71. [PMID:20940043]

Schappi JM, Krbanjevic A, Rasenick MM. (2014) Tubulin, actin and heterotrimeric G proteins: coordination of signaling and structure. Biochim Biophys Acta, 1838 (2): 674-81. [PMID:24071592]

Song Y, Brady ST. (2015) Post-translational modifications of tubulin: pathways to functional diversity of microtubules. Trends Cell Biol, 25 (3): 125-36. [PMID:25468068]

Yu I, Garnham CP, Roll-Mecak A. (2015) Writing and Reading the Tubulin Code. J Biol Chem, 290 (28): 17163-72. [PMID:25957412]

* Zhang YF, Huang J, Zhang WX, Liu YH, Wang X, Song J, Jin CY, Zhang SY. (2023) Tubulin degradation: Principles, agents, and applications. Bioorg Chem, 139: 106684. [PMID:37356337]

1. Cifuentes M, Schilling B, Ravindra R, Winter J, Janik ME. (2006) Synthesis and biological evaluation of B-ring modified colchicine and isocolchicine analogs. Bioorg Med Chem Lett, 16 (10): 2761-4. [PMID:16504507]

2. Gangjee A, Zhao Y, Raghavan S, Rohena CC, Mooberry SL, Hamel E. (2013) Structure-activity relationship and in vitro and in vivo evaluation of the potent cytotoxic anti-microtubule agent N-(4-methoxyphenyl)-N,2,6-trimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-aminium chloride and its analogues as antitumor agents. J Med Chem, 56 (17): 6829-44. [PMID:23895532]

3. Narayan S, Carlson EM, Cheng H, Condon K, Du H, Eckley S, Hu Y, Jiang Y, Kumar V, Lewis BM et al.. (2011) Novel second generation analogs of eribulin. Part III: Blood-brain barrier permeability and in vivo activity in a brain tumor model. Bioorg Med Chem Lett, 21 (6): 1639-43. [PMID:21324687]

4. Ouyang X, Piatnitski EL, Pattaropong V, Chen X, He HY, Kiselyov AS, Velankar A, Kawakami J, Labelle M, Smith 2nd L et al.. (2006) Oxadiazole derivatives as a novel class of antimitotic agents: Synthesis, inhibition of tubulin polymerization, and activity in tumor cell lines. Bioorg Med Chem Lett, 16 (5): 1191-6. [PMID:16377187]