Cell internalizing compounds
View Patent ↗Provided herein are cell penetrating compounds having the Formula I: where, generally, each T is a thiol reactive group (e.g., a phosphorothioate), each L is a linker (e.g., a linear alkyl), and Y is a biologic (e.g., an antibody). Also provided are pharmaceutical compositions including the cell penetrating compounds, and methods of delivering the compound into a cell.
1. A compound having the Formula II:
or a pharmaceutically acceptable salt thereof, wherein:
each R is CH 3 or H;
each L is independently a polyethylene glycol (PEG), a linear alkyl, or a cyclic alkyl;
Y is a protein, an antibody, a peptide, or a nucleic acid; and
n is an integer from 5 to 25.
2. The compound of claim 1 , wherein n is an integer from 12 to 20.
3. The compound of claim 1 , wherein n is 15, 16 or 17.
4. The compound claim 1 , wherein each L is a linear alkyl.
5. The compound of claim 1 , wherein each L is independently a linear (C 2 -C 6 )alkyl, or a cyclic (C 5 -C 6 )alkyl, or —(O—CH 2 —CH 2 ) p —, wherein p is an integer from 1 to 5.
6. The compound of claim 1 , wherein each L is —CH 2 —.
7. The compound of claim 1 , wherein each L is —(O—CH 2 —CH 2 ) p —, wherein p is an integer from 1 to 5.
8. The compound of claim 1 , wherein each R is H, each L is —CH 2 —, n is 15, 16 or 17, and Y is an antibody.
9. The compound of claim 8 , wherein n is 16.
10. The compound of claim 1 , wherein Y is an antibody or antibody fragment.
11. The compound of claim 1 , wherein Y is a peptide.
12. The compound of claim 1 , wherein Y is a protein.
13. The compound of claim 1 , wherein Y is a nucleic acid.
14. A pharmaceutical composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.
15. A method of delivering a therapeutic agent into a cell comprising contacting a cell with a compound of claim 1 or a pharmaceutical composition comprising the compound or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, wherein the compound is internalized into the cell.
16. A pharmaceutical composition comprising the compound of claim 12 , or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.
17. A method of delivering a therapeutic agent into a cell comprising contacting a cell with a compound of claim 1 or a pharmaceutical composition comprising the compound or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, wherein the compound is internalized into the cell.