US 11,730,750 B2
Drugs for GRP78 cell surface translocation and Par-4 secretion
Vivek M. Rangnekar, Nicholasville, KY (US); Ravshan Burikhanov, Lexington, KY (US); and David S. Watt, Lexington, KY (US)
Assigned to University of Kentucky Research Foundation, Lexington, KY (US)
Filed by University of Kentucky Research Foundation, Lexington, KY (US)
Filed on Feb. 17, 2021, as Appl. No. 17/178,096.
Claims priority of provisional application 62/977,582, filed on Feb. 17, 2020.
Prior Publication US 2021/0252032 A1, Aug. 19, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/7048 (2006.01); A61K 45/06 (2006.01); A61K 31/4706 (2006.01); A61K 31/704 (2006.01); A61K 31/55 (2006.01); A61K 31/4545 (2006.01); A61K 31/675 (2006.01); A61K 31/497 (2006.01); A61K 31/517 (2006.01); A61K 31/4745 (2006.01)
CPC A61K 31/7048 (2013.01) [A61K 31/4545 (2013.01); A61K 31/4706 (2013.01); A61K 31/4745 (2013.01); A61K 31/497 (2013.01); A61K 31/517 (2013.01); A61K 31/55 (2013.01); A61K 31/675 (2013.01); A61K 31/704 (2013.01); A61K 45/06 (2013.01)] 7 Claims
 
1. A method of treating lung cancer in an individual, comprising: administering to the individual a pharmaceutically effective amount of (a) a first active agent adapted for producing secretion of prostate apoptosis response-4 (Par-4) from normal cells and (b) a second active agent adapted for elevating GRP78 receptors for Par-4 on a surface of a cancer cell in the individual wherein the the first active agent is selected from a first group of agents consisting of chloroquine, hydroxychloroquine, etoposide, doxorubicin, Nutlin, irinotecan and combinations thereof and the second active agent is selected from a second group of agents consisting of crizotinib, brigatinib, lorlatinib, alectinib, sepantronium bromide (YM155), afatinib, gefitinib, erlotinib, osimertinib, alisertib, barasertib, danusertib, 1-Cyclopropyl-3-[3-(5-morpholin-4-ylmethyl-1H-benzoimidazol-2-yl)-1H-pyrazol-4-yl]-urea (AT9283), N-(2-((1S,4R)-6-((4-(Cyclobutylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1,2,3,4-tetrahydro-1,4-epiminonaphthalen-9- yl)-2- oxoethyl)acetamide (PF-03814735), N-[4-[3-(2-aminopyrimidin-4-yl)pyridin-2-yl]oxyphenyl]-4-(4-methylthiophen-2-yl)phthalazin-1-amine (AMG900) and combinations thereof and the second active agent is administered at a dosage rate of 400 mg/day.