Claims for Patent: 8,877,795

Summary for Patent: 8,877,795

Title:	Identification of stabilizers of multimeric proteins
Abstract:	Disclosed herein are compounds and compositions thereof which find use in increasing stability of TTR tetramers reducing its tendency to misfold and form aggregates. Also provided herein are methods for using these compounds and compositions for increasing stability of TTR and thereby decreasing aggregate formation by TTR. Also disclosed herein are methods to screen for candidate compounds that increase stability of TTR. Also disclosed herein are heterobifunctional compounds that include a TTR binding compound connected to a targeting moiety via a linker, for use in disrupting PPIs of a target protein.
Inventor(s):	Isabella A. Graef, Mamoun Alhamadsheh
Assignee:	Leland Stanford Junior University
Application Number:	US13/696,505
Patent Claims:	1. A pharmaceutical composition comprising a compound of formula (XVII): wherein L is a linker of about 1 to 8 atoms in length; R51 and R52 are selected from an alkyl, an aryl, an alkoxy, an aryloxy, a hydroxyl, a heterocyclic group, a halo, a nitro and a cyano; R53 is selected from hydrogen, an alkyl, an aryl and a heterocyclic group; and R54 is an aryl group. 2. The pharmaceutical composition of claim 1, wherein the composition further comprises at least one of a pharmaceutically acceptable carrier, a pharmaceutically acceptable diluent, a pharmaceutically acceptable excipient and a pharmaceutically acceptable adjuvant. 3. The pharmaceutical composition of claim 1, wherein the composition does not contain detectable dimethyl sulfoxide. 4. The pharmaceutical composition of claim 1, wherein the compound is of the structure of Formula XVIII: wherein n is 1, 2, 3 or 4; R55, R56, and R57 are as defined above for R51, R52, and R53; and R58 is selected from an aryl, an aryloxy and a heterocyclic group. 5. The pharmaceutical composition of claim 4, wherein R58 has the structure: 6. The pharmaceutical composition of claim 4, wherein: n is 2 or 3; R55 and R56 are methyl; R57 is hydrogen; and R58 is selected from an aryl, an aryloxy and a heterocyclic group. 7. The pharmaceutical composition of claim 1, wherein the compound is of the structure of one of formulas XIX and XX: wherein L is a linker of about 1 to 8 atoms in length; n is 1, 2, 3 or 4; R61 and R62 are selected from hydrogen, an alkyl, an aryl, an alkoxy, an aryloxy, a hydroxyl, a heterocyclic group, a halo, a nitro and a cyano; R63 is selected from hydrogen, an alkyl, an aryl and a heterocyclic group; and R64 and R68 are independently one or more groups, each R64 and R68 independently selected from an alkyl, an aryl, an alkoxy, an aryloxy, an acetyl, a carboxy, a formyl, an amido, a hydroxyl, a heterocyclic group, a halo, a nitro and a cyano, wherein optionally two or more R64 or R68 groups may be cyclically linked. 8. The pharmaceutical composition of claim 7, wherein n is 2 or 3; R61, R62, R65 and R66 are methyl; R63 is R67 are hydrogen; and R64 and R67 are independently selected from an aryl, an aryloxy and a heterocyclic group.