Small molecules that specifically inhibit TNF-induced NF-KB inflammation pathway
AssigneeUniversity of Pittsburgh—Of the Commonwealth System of Higher Education
InventorsCarlos Jaime Camacho, Robin E. C. Lee
Life of this patent
Estimating the term…
Abstract
Provided herein are small molecules that specifically inhibit TNF-induced nuclear factor kB (NF-kB) inflammation pathway. Also provided are methods of screening compounds to identify molecules that specifically inhibit a TNF-induced NF-kB inflammation pathway, methods of inhibiting TNF-induced NF-kB inflammation pathway, and methods of preventing formation of mature TNFR1 complex.
Claims21
A compound represented by formula (I):
- or a salt or hydrate thereof, wherein:
- A is an azinic acid;
- B is an alkyl sulfonyl;
- X1 and X3 are independently selected from O, NOH, NO-alkyl, and C(CN)2;
- X2 is selected from O, NH, and NF;
- R1 is H or alkyl and R2 is an optionally substituted alkyl or cycloalkyl, or R1 and R2 together form an optionally substituted 5- or 6-membered heterocycle;
- and
- R3 is selected from H, F, and an optionally substituted alkyl, where the compound of formula (I) is not:
A method of preventing formation of mature TNFR1 complex, comprising contacting a cell with a compound of formula (I):
- or a salt or hydrate thereof, wherein:
- A is an azinic acid;
- B is an alkyl sulfonyl;
- X1 and X3 are independently selected from O, NOH, NO-alkyl, CF3, and C(CN)2;
- X2 is selected from O, NH, and NF;
- R1 is H or alkyl and R2 is an optionally substituted alkyl or cycloalkyl, or R1 and R2 together form an optionally substituted 5- or 6-membered heterocycle.
A method of inhibiting a TNF-induced nuclear factor kB (NF-kB) inflammation pathway, comprising contacting a cell with a compound of formula (I):
- or a salt or hydrate thereof, wherein:
- A is an azinic acid;
- B is an alkyl sulfonyl;
- X1 and X3 are independently selected from O, NOH, NO-alkyl, CF3, and C(CN)2;
- X2 is selected from O, NH, and NF;
- R1 is H or alkyl and R2 is an optionally substituted alkyl or cycloalkyl, or R1 and R2 together form an optionally substituted 5- or 6-membered heterocycle.
Dependencies are inferred from the claim text.