Multifunctional linker technology containing an N4 group
In some aspects, the present disclosure provides compositions comprising an N4-based MMC ligand, a cell targeting group, and a fluorophore or a therapeutic compound comprising a formula: wherein the variables are as defined herein. In some embodiments, these compositions may be used in the imaging techniques or in the treatment of a disease or disorder such as cancer.
1. A compound of the formula:
wherein:
L 1 is a covalent bond, —CH 2 C(O)—, or a thiol reactive group;
L 2 is a covalent bond or —CH 2 C(O)—;
M is a metal atom of any oxidation state or absent;
R 1 and R 3 are each independently -A-COR 5 , wherein:
A is alkanediyl (C≤8) or substituted alkanediyl (C≤8) ; and
R 5 is hydroxy, alkoxy (C≤8) , or substituted alkoxy (C≤8) ;
R 2 is a cell-targeting moiety, wherein the cell-targeting moiety is a peptide or an antibody; and
R 4 is a fluorophore group or a chemotherapeutic group, wherein the fluorophore group emits light from about 675 nm to about 2500 nm;
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein R 1 and R 3 are both -A-COR 5 , wherein: A is alkanediyl (C≤8) or substituted alkanediyl (C≤8) ; and R 5 is hydroxy, alkoxy (C≤8) , or substituted alkoxy (C≤8) .
3. The compound of claim 2 , wherein A is alkanediyl (C≤8) .
4. The compound of claim 3 , wherein A is —CH 2 —.
5. The compound of claim 1 , wherein the cell-targeting moiety is a peptide.
6. The compound of claim 5 , wherein the peptide comprises from 2 to 100 amino acids.
7. The compound of claim 6 , wherein the peptide is of the formula:
8. The compounds of claim 1 , wherein the cell-targeting moiety targets PSMA.
9. The compound of claim 1 , wherein the cell-targeting moiety is an antibody.
10. The compound of claim 9 , wherein the antibody targets CD20, CD22, CD30, CD52, HER2, VEGF, VEGFR2, EGFR, PD-1, PD-L1, EpCAM, AR, or PSMA.
11. The compound of claim 1 , wherein the chemotherapeutic group is selected from a nucleoside analog, an alkylating agent, a topoisomerase inhibitor, a mitotic inhibitor, duocarmycin or duocarmycin analogs, maitansine or maitansine analogs, dolostatin or dolostatin analogs.
12. The compound of claim 1 , wherein the fluorophore group further comprises a linker which joins the fluorophore to formula I, further wherein the linker comprises a triazole group.
13. The compound of claim 1 , wherein M is a transition metal atom radionuclide.
14. The compound of claim 1 , wherein M is a transition metal atom radionuclide, further wherein the radionuclide is 45 Ti, 59 Fe, 60 Cu, 61 Cu, 62 Cu, 64 Cu, 67 Cu, 67 Ga, 68 Ga, 89 Sr, 90 Y, 94m Tc, 99m Tc, 111 In, 149 Pm, 153 Gd, 153 Sm, 166 Ho, 177 Lu, 186 Re, 188 Re, 211 At, 212 Bi, or 225 AC.
15. The compound of claim 14 , wherein the radionuclide is 64 Cu or 68 Ga.
16. The compound of claim 15 , wherein the radionuclide is 64 Cu.
17. The compound of claim 15 , wherein the radionuclide is 68 Ga.
18. The compound of claim 1 further defined as:
wherein:
R a is a peptide comprising from 2 amino acids to 100 amino acids;
or a pharmaceutically acceptable salt thereof.
19. The compound of claim 18 , wherein the peptide is of the formula: