Epothilone D


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Name: Epothilone D
Synonyms: BMS-241027
Therapy Type: Small Molecule (timeline)
Target Type: Tau (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Discontinued)
Company: Bristol-Myers Squibb


BMS-241027 is a small-molecule microtubule stabilizer for the treatment of Alzheimer's disease. One of tau's physiological cellular functions is to bind and stabilize microtubules. This function is lost in tauopathies as hyperphosphorylated and otherwise aberrant tau dissociates from microtubules, leading to neurodegeneration and subsequent cognitive decline. The rationale of BMS-241027 is that stabilizing microtubules may be beneficial in Alzheimer's and other tauopathies.

Unlike other Epothilone D compounds that have been studied in oncology, BMS-241027 is comparably safe and crosses the blood-brain barrier. Epothilone D was shown to be effective at low concentrations (see Brunden et al., 2010).

In rTg4510 mice expressing mutant human tau, BMS-241027 restored a spatial memory deficit. It also reduced hippocampal neuronal loss and various types of histological neuropathology (see Aug 2008 news story). ). In both young and old animals of the (P301S)PS19 tauopathy model, in which tau pathology is developing or well established, respectively, BMS-241027 reversed behavioral and cognitive deficits, cleared tau pathology, and curbed neuron loss (see Hurtado et al., 2010Mar 2012 news storyZhang et al., 2012). Dosing young versus old mice serves to model preventive and intervention treatment, respectively.


In February 2012, Bristol-Myers Squibb started a Phase 1 trial to evaluate the tolerability and pharmacology of BMS-241027 in 40 patients with mild Alzheimer's disease whose MMSE at screening was between 20 and 26. The trial compares 0.003, 0.01, and 0.03 mg/kg infused once a week for nine weeks to placebo. It monitors adverse effects and measures whether the drug changes cerebrospinal fluid (CSF) concentrations of the N-terminal fragment of tau. Secondary endpoints include CSF concentration of the mid-domain tau fragment, cognitive performance on computerized cognitive tests, connectivity MRI, and various pharmacodynamic measures of the drug in plasma. The study ended in October 2013, and evaluation of epothilone D for Alzheimer's disease was subsequently discontinued.

Last Updated: 05 Aug 2014


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Research Models Citations

  1. rTg(tauP301L)4510
  2. Tau P301S (Line PS19)

News Citations

  1. Chicago: Brain-Penetrant Microtubule Stabilizer in Tauopathy Mice
  2. Paper Alert: Microtubule Stabilizer Improves Tauopathy in Mice

Paper Citations

  1. . Epothilone D improves microtubule density, axonal integrity, and cognition in a transgenic mouse model of tauopathy. J Neurosci. 2010 Oct 13;30(41):13861-6. PubMed.
  2. . A{beta} accelerates the spatiotemporal progression of tau pathology and augments tau amyloidosis in an Alzheimer mouse model. Am J Pathol. 2010 Oct;177(4):1977-88. PubMed.
  3. . 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 Mar 14;32(11):3601-11. PubMed.

Further Reading


  1. . Brain-penetrant microtubule-stabilizing compounds as potential therapeutic agents for tauopathies. Biochem Soc Trans. 2012 Aug;40(4):661-6. PubMed.
  2. . The characterization of microtubule-stabilizing drugs as possible therapeutic agents for Alzheimer's disease and related tauopathies. Pharmacol Res. 2011 Apr;63(4):341-51. PubMed.