Methods and compositions related to a retinoid receptor-selective pathway
Provided herein are methods and compositions related to a retinoid receptor-selective pathway. As described herein, this pathway can be targeted to manipulate a tumor microenvironment. For example, the methods and compositions described herein can be used to induce apoptosis in a cancer cell. Further, the compositions described herein, including Sulindac and analogs thereof, can be used to target this pathway for the treatment or prevention of cancer in human patients.
1. A compound of formula (I), or a sodium salt thereof, having the structure:
wherein A is a phenyl, and wherein A is substituted by one or two substituents independently selected from the group consisting of C2-3 alkyl, n-butyl, iso-butyl, sec-butyl, —CF 3 , a C3-C4 cycloalkyl, and a C4-C5 cycloalkylalkyl;
wherein B is a fused phenyl, and wherein B is substituted by a fluoro;
wherein R 1 is —(CR 5 R 6 ) n COOH;
wherein R 2 is CH 3 ;
wherein R 5 and R 6 are H; and
wherein n is 1 or 2.
2. A compound of formula (II), or a sodium salt thereof, having the structure:
wherein R 1 is selected from the group consisting of CH 2 COOH and CH 2 CH 2 COOH;
wherein R 2 is CH 3 ; and
wherein R 3 is selected from the group consisting of 4-CH 2 CH 3 , and 4-CH(CH 3 ) 2 .
3. The compound of claim 2 , or a sodium salt thereof, selected from the group consisting of:
4. The compound of claim 2 , or a sodium salt thereof, selected from the group consisting of:
5. The compound of claim 2 , or a sodium salt thereof, having the structure:
6. A compound, or a sodium salt thereof, having the structure:
7. A pharmaceutical composition comprising a compound of claim 1 , or a sodium salt thereof, and a pharmaceutically acceptable excipient.
8. A pharmaceutical composition comprising a compound of claim 2 , or a sodium salt thereof, and a pharmaceutically acceptable excipient.
9. A pharmaceutical composition comprising a compound of claim 6 , or a sodium salt thereof, and a pharmaceutically acceptable excipient.