US 11,883,459 B2
Thiol isomerases inhibitors for the treatment and prevention of food allergies, allergic diseases, and inflammatory diseases
Daniel Kennedy, Longmeadow, MA (US); and Clinton Mathias, Wilbraham, MA (US)
Assigned to WESTERN NEW ENGLAND UNIVERSITY, Springfield, MA (US)
Appl. No. 16/971,186
Filed by WESTERN NEW ENGLAND UNIVERSITY, Springfield, MA (US)
PCT Filed Feb. 20, 2019, PCT No. PCT/US2019/018679
§ 371(c)(1), (2) Date Aug. 19, 2020,
PCT Pub. No. WO2019/164874, PCT Pub. Date Aug. 29, 2019.
Claims priority of provisional application 62/632,717, filed on Feb. 20, 2018.
Prior Publication US 2021/0128679 A1, May 6, 2021
Int. Cl. A61K 38/00 (2006.01); A61K 38/12 (2006.01); A61P 37/08 (2006.01); A61K 31/381 (2006.01); A61K 31/7048 (2006.01); A61K 45/06 (2006.01)
CPC A61K 38/12 (2013.01) [A61K 31/381 (2013.01); A61K 31/7048 (2013.01); A61K 45/06 (2013.01); A61P 37/08 (2018.01)] 9 Claims
 
1. A method of treating, inhibiting, or preventing the development of a food allergy in a patient, comprising: administering a therapeutically effective amount of two thiol isomerase inhibitors to a patient in need thereof;
wherein the thiol isomerase inhibitor is a protein disulfide isomerase inhibitor; and wherein the thiol isomerase inhibitor is a compound in the class of propynoic acid carbamoyl methyl amides (PACMAs) selected from the group consisting of PACMA 31 (N-(2,4-dimethoxypheny 1)-N-(1-oxo-2- propyn-1-yl)-2-(2-thienyl)glycylglycine ethyl ester); juniferdin; juniferdin epoxide; phenylarsine oxide; LOC 14 (2-1 14-(cyclopropylcarbonyl)-1-piperazinyllmethy 11-1,2-benzisothiazol-3(2H)-one); CCF 642 (3-(4-methoxypheny 1)-5- 1(5-nitro-2- thienyl)methylene 1-2-thioxo-4-thiazolidinone); P1 (N- 1(1,1-dimethylethoxy)carbonyll-L - phenylalanyl1-O -(ethenylsulfonyl1)-N-4-pentyn-1-yl-L-tyrosinamide); 1 6F1 6 (2-(2- chloroacety 1)-2,3 ,4,9-tetrahydro-1-methyl-1H-pyrido13,4-blindole-1-carboxylic acid methyl ester); ML359 (ethyl 1- (3-chloro-4-hydroxybenzy 1)-4-(2-phenoxyethyl)piperidine-4- carboxylate); zafirlukast; CGP -13501; CGP-7930; alosetron; balsalazide; benserazide; butaclamol; oxcarbazepine; or combination thereof, or a protein disulfide isomerase inhibitor targeting antibody, selected from the group consisting of protein disulfide isomerase inhibitor antibody RL90, or MA3-0 19 and wherein the therapeutically effective amount of the two thiol isomerase inhibitors are formulated as a pharmaceutical composition suitable for administration orally, parenterally, or transdermally.