US 11,739,326 B2
RUNX1 inhibition for treatment of proliferative vitreoretinopathy and conditions associated with epithelial to mesenchymal transition
Leo A. Kim, Brookline, MA (US); Joseph F. Arboleda-Velasquez, Newtown, MA (US); Dhanesh Amarnani, Allston, MA (US); and Dean Eliott, Carlsbad, CA (US)
Assigned to Massachusetts Eye and Ear Infirmary, Boston, MA (US); and The Schepens Eye Research Institute, Inc., Boston, MA (US)
Appl. No. 16/763,880
Filed by The Schepens Eye Research Institute, Inc., Boston, MA (US); and Massachusetts Eye and Ear Infirmary, Boston, MA (US)
PCT Filed Nov. 14, 2018, PCT No. PCT/US2018/061110
§ 371(c)(1), (2) Date May 13, 2020,
PCT Pub. No. WO2019/099560, PCT Pub. Date May 23, 2019.
Claims priority of provisional application 62/586,067, filed on Nov. 14, 2017.
Prior Publication US 2020/0377888 A1, Dec. 3, 2020
Int. Cl. C12N 15/113 (2010.01); A61P 27/02 (2006.01); A61K 9/00 (2006.01); A61K 31/4025 (2006.01); A61K 31/5513 (2006.01); A61K 31/7105 (2006.01); A61K 45/06 (2006.01); G01N 33/68 (2006.01)
CPC C12N 15/113 (2013.01) [A61K 9/0048 (2013.01); A61K 31/4025 (2013.01); A61K 31/5513 (2013.01); A61K 31/7105 (2013.01); A61K 45/06 (2013.01); A61P 27/02 (2018.01); G01N 33/6893 (2013.01); C12N 2310/14 (2013.01); G01N 2333/4706 (2013.01); G01N 2800/164 (2013.01)] 33 Claims
 
1. A method for preventing or reducing proliferation or migration of retinal pigment epithelial (RPE) cells in a subject who has not been diagnosed with aberrant angiogenesis or small vessel disease and who comprises a retinal hole or retinal tear, the method comprising administering to the subject a composition comprising a small molecule selected from the group consisting of:
a small molecule comprising the structure of Formula I:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt or ester thereof, wherein
each R1 is individually selected from halogen, alkyl, aryl, heteroaryl, or alkoxy,
and R1 is selected from aryl or heteroaryl, and
a is 0 to 4; or
a small molecule comprising the structure of Formula III:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt or ester thereof, wherein
each R1 is individually selected from halogen, alkyl, aryl, heteroaryl, or alkoxy,
R2 is selected from aryl or heteroaryl;
R3 is alkyl or aryl, and
a is 0 to 4; or
a small molecule comprising the structure of Formula V:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt or ester thereof, wherein
R1 is H3, NH2, or NHC(O)CH3, and
X is CH2 or C(O).