Structure-based design of a novel class of drugs for neurodegenerative disease
AssigneeThe Regents of the University of California
InventorsDavid S. Eisenberg, Paul M. Seidler, Kevin A. Murray, David R. Boyer, Jiahui Lu
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Abstract
The invention provides pharmaceutical compositions comprising molecules capable of disassembling tau amyloid fibrils or alpha-synuclein amyloid fibrils, as well as methods for making compositions comprising these molecules. Embodiments of the invention also include methods for using these molecules to facilitate the disassembling of tau amyloid fibrils or alpha-synuclein amyloid fibrils.
Claims20
A composition of matter comprising at least one of:
- CNS-2;
- CNS-11;
- CNS-11G;
- CNS-12;
- CNS-17;
- MOL01;
- MOL06;
- MOL18;
- or
- 1541;
- and
- a pharmaceutically acceptable carrier.
A method of making a pharmaceutical composition comprising combining at least one of:
- CNS-2;
- CNS-11;
- CNS-11G;
- CNS-12;
- CNS-17;
- MOL01;
- MOL06;
- MOL18;
- or
- 1541;
- with a pharmaceutically acceptable excipient such that the pharmaceutical composition is made.
A method of identifying agents capable of binding amyloid fibrils comprising;
- disposing fibrils in an aqueous solution in a container;
- combining the fibrils with one or more test agents;
- and
- observing the ability of the one or more test agents to bind the fibrils;
- wherein the method includes:
- observing binding of the one or more agents to a pharmacophore on fibrils that is bound by epigallocatechin gallate (EGCG) such as site 1 binding clefts.
A method of inhibiting the aggregation of and/or facilitating disaggregating fibrils of tau or alpha-synuclein proteins comprising combining the fibrils of tau or alpha-synuclein proteins with at least one of CNS-2;
- CNS-11;
- CNS-11G;
- CNS-12;
- CNS-17;
- MOL01;
- MOL06;
- MOL18;
- or 1541 such that the aggregation of and/or facilitating the disaggregating fibrils of tau or alpha-synuclein proteins is inhibited.
A method for treating a subject having an amyloid disease characterized by aggregation of tau amyloid fibrils or aggregation of alpha-synuclein amyloid fibrils, comprising administering to the subject an effective amount of a pharmaceutical composition comprising at least one of:
- CNS-2;
- CNS-11;
- CNS-11G;
- CNS-12;
- CNS-17;
- MOL01;
- MOL06;
- MOL18;
- or
- 1541;
- and
- a pharmaceutically acceptable excipient.
A method of inhibiting formation of tau fibrils comprising:
- combining tau with a composition at least one of:
- CNS-2;
- CNS-11;
- CNS-12;
- CNS-17;
- MOL18 and 1541;
- and
- a pharmaceutically acceptable carrier;
- and
- allowing the CNS-2;
- CNS-11;
- CNS-12;
- CNS-17;
- MOL18 and 1541 to bind to tau;
- so that Tau fibril formation is inhibited.
Dependencies are inferred from the claim text.