Easton Center - Pilot Project 13.1: Examination of a Novel Drug Candidate for Alzheimer’s Disease in a Translational Animal Model


  • S Sinha, DHJ Lopes, Z Du, ES Pang, A Shanmugam, A Lomakin, P Talbiersky, A Tennstaedt, K McDaniel, R Bakshi, P-Y Kuo, M Ehrmann, GB Benedek, JA Loo, F-G Klärner, T Schrader, C Wang, and G Bitan. Lysine-specific molecular tweezers are broad-spectrum inhibitor of aggregation and toxicity of amyloid proteins. J. Am. Chem. Soc2011; 133(42): 16958–16969.
  • S Sinha, Z Du, P Maiti, F-G Klärner, T Schrader, C Wang, and G Bitan. Comparison of Three Amyloid Assembly Inhibitors: The Sugar scyllo-Inositol, the Polyphenol Epigallocatechin Gallate, and the Molecular Tweezer CLR01. ACS Chem. Neurosci2012; 3(6): 451-458.
  • S Sinha, DHJ Lopes, and G Bitan. A Key Role for Lysine Residues in Amyloid β-Protein Folding, Assembly, and Toxicity. ACS Chem. Neurosci2012; 3(6): 473-481.
  • T Liu and G Bitan. Modulating Self-Assembly of Amyloidogenic Proteins as a Therapeutic Approach for Neurodegenerative Diseases: Strategies and Mechanisms. ChemMedChem2012; 7: 359-374.
  • A Attar, C Ripoli, E Riccardi, P Maiti, DD Li Puma, T Liu, J Hayes, MR Jones, K Lichti-Kaiser, F Yang, GD Gale, C-h Tseng, M Tan, C-W Xie, JL Straudinger, F-G Klärner, T Schrader, SA Frautschy, C Grassi and G Bitan. Protection of primary neurons and mouse brain from Alzheimer’s pathology by molecular tweezers. Brain2012; 135(Pt 12): 3735-3748.
  • A Attar, F Rahimi, and G Bitan. Modulators of amyloid protein aggregation and toxicity: EGCG and CLR01. Translational Neuroscience2013; 4(4): 385-409.
  • A Attar, W-TC Chan, F-G Klärner, T Schrader, and G Bitan. Safety and pharmacological characterization of the molecular tweezer CLR01 – a broad-spectrum inhibitor of amyloid proteins’ toxicity. BMC Pharm. Tox2014; 15(23): doi:10.1186/2050-6511-15-23.
  • A Attar and G Bitan. Disrupting self-assembly and toxicity of amyloidogenic protein oligomers by ” molecular tweezers” – from the test tube to animal models, Curr. Pharm. Des. 2014; 20: 2469-2483.
  • X Zheng, D-Y Liu, F-G Klärner, T Schrader, G Bitan, and MT Bowers. Amyloid β-protein Assembly: The Effect of Molecular Tweezer CLR01 and CLR03. J. Phys. Chem. B2015; 119: 4831-4841.
  • R Malishev, S Nandi, S Kolusheva, Y Levi-Kalisman, F-G Klärner, T Schrader, G Bitan*, and R Jelinek*, Toxicity inhibitors protect lipid membranes from disruption by Aβ42, ACS Chem. Neurosci. 2015; 6: 1860-1869.
  • T Schrader, G Bitan, and F-G Klärner, Molecular Tweezers for Lysine and Arginine – Powerful Inhibitors of Pathologic Protein Aggregation, Chem. Commun. 2016; 52: 11318-11334.
  • R Malik, J Di, G Nair, A Attar, K Taylor, E Teng, F-G Klärner, T Schrader, and G Bitan, Using molecular tweezers to remodel abnormal protein self-assembly and inhibit the toxicity of amyloidogenic proteins.Methods Mol. Biol. 2018, 1777: 369-386.
  • M Nshanian, C Lantz, P Wongkongkathep, T Schrader, F-G Klärner, A Blümke, C Despres, M Ehrmann, C Smet-Nocca, G Bitan, and JA Loo,  Native Top-Down Mass Spectrometry and Ion Mobility Spectrometry of the Interaction of Tau Protein with a Molecular Tweezer Assembly Modulator J. Am. Soc. Mass Spectrom2018,DOI: 10.1007/s13361-018-2027-6.
  • C Despres, J Di, F-X Cantrelle, Z Li, I Huvent, B Chambraud, J Zhao, J Chen, S Chen, G Lippens, F Zhang, R Linhardt, C Wang, F-G Klärner, T Schrader, I Landrieu, G Bitan, and Caroline Smet-Nocca (2019) Major differences between the self-assembly and seeding behavior of heparin-induced- and in-vitro-phosphorylated tau and their modulation by potential inhibitors. ACS Chem. Biol., 14: 1363-1379.
  • I Hadrovic, P Rebmann, F-G Klärner, G Bitan, and T Schrader (2019) Molecular Lysine Tweezers Counteract Aberrant Protein Aggregation. Front. Chem. 7: 657.
  • AJ Mason, I Hurst, R Malik, I Siddique, I Solomonov, I Sagi, F-G Klärner, T Schrader, and G Bitan (2020) Different Inhibitors of Aβ42-Induced Toxicity Have Distinct Metal-Ion Dependency. ACS Chem. Neurosci. 11: 2243–2255.
  • J Di, I Siddique, Z Li, G Malki, S Hornung, S Dutta, I Hurst, E Ishaaya, A Wang, S Tu, A Boghos, I Ericsson, F-G Klärner, T Schrader, and G Bitan (2021) The molecular tweezer CLR01 improves behavioral deficits and reduces tau pathology in P301S-tau transgenic mice. Alz. Res. Ther., 13: 6.


  • 2011-2012 Cure Alzheimer’s Fund “Molecular tweezers – novel inhibitors of amyloidogenic proteins and promising drug candidates for Alzheimer’s disease”
  • 2012 NIH/NCRR UL1 TR000124 – UCLA Clinical and Translational Science Institute (CTSI) Voucher “A mouse toxicity study of a novel drug candidate”
  • 2015-2016 Cure Alzheimer’s Fund 20152631 “Optimization of pharmacologic properties of molecular tweezers”
  • 2015-2017 CurePSP Foundation 600-6-15 “Small-molecule modulation of tau clearance and aggregation”
  • 2015-2020 NIH/NIA R01AG050721 “Misfolded protein clearance enhancers for Alzheimer’s therapy”

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