Invention Grant
- Patent Title: Small molecules that covalently modify transthyretin
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Application No.: US14252251Application Date: 2014-04-14
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Publication No.: US09771321B2Publication Date: 2017-09-26
- Inventor: Jeffery W Kelly , Sungwook Choi
- Applicant: Jeffery W Kelly , Sungwook Choi
- Applicant Address: US CA La Jolla
- Assignee: THE SCRIPPS RESEARCH INSTITUTE
- Current Assignee: THE SCRIPPS RESEARCH INSTITUTE
- Current Assignee Address: US CA La Jolla
- Agency: Husch Blackwell LLP
- Main IPC: A61K31/21
- IPC: A61K31/21 ; C07C327/26 ; A61K31/136 ; C07C39/21 ; C07C65/19 ; C07C69/94 ; C07C205/43 ; C07C229/64 ; C07C237/30 ; C07C245/08 ; C09B23/14 ; C09B29/01 ; C09B29/036 ; C09B29/033 ; C09B29/10 ; C09B29/12 ; G01N33/68 ; G01N33/74

Abstract:
A family of covalent kinetic stabilizer compounds that selectively and covalently react with the prominent plasma protein transthyretin in preference to more than 4000 other human plasma proteins is disclosed. A contemplated compound corresponds in structure to Formula I, below, where the various substituents are defined within, and reacts chemoselectively with one or two of four Lys-15 ε-amino groups within the transthyretin tetramer. The crystal structure confirms the binding orientation of the compound substructure and the conjugating amide bond. A covalent transthyretin kinetic stabilizer exhibits superior amyloid inhibition potency, compared to a non-covalent counterpart, and inhibits cytotoxicity associated with amyloidogenesis.
Public/Granted literature
- US20170190660A9 Small Molecules That Covalently Modify Transthyretin Public/Granted day:2017-07-06
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