PSMA binding ligand-linker conjugates and methods for using
Described herein are prostate specific membrane antigen (PSMA) binding conjugates that are useful for delivering therapeutic, diagnostic and imaging agents. Also described herein are pharmaceutical composition containing them and methods of using the conjugates and compositions. Also described are processes for manufacture of the conjugates and the compositions containing them.
1. A compound of the formula:
B-L-D
or a salt thereof, wherein
B comprises a urea of two amino acids, wherein each amino acid is independently an aminoalkylcarboxylate substituted with alkyl, hydroxyalkyl, sulfhydrylalkyl, aminoalkyl, or carboxyalkyl;
L comprises at least one hydrophobic side chain group that is arylalkyl comprising a naphthyl group and is 14 to 24 atoms in length; and
D is a radioisotope.
2. The compound of claim 1 or a salt thereof, wherein B is of the formula
wherein R 1 is hydrogen and R 2 is a substituted carboxylic acid, wherein the substituted carboxylic acid is covalently hound to the linker.
3. The compound of claim 1 or a salt thereof, wherein L comprises one or more Arg, Lys, Asp, Glu, and Gln.
4. The compound of claim 3 or a salt thereof, wherein L comprises Glu.
5. The compound of claim 2 or a salt thereof, wherein L comprises one or more Arg, Lys, Asp, Glu, and Gln.
6. The compound of claim 5 or a salt thereof, wherein L comprises Glu.
7. A pharmaceutical composition comprising a compound of claim 1 or a salt thereof and at least one pharmaceutically acceptable carrier, excipient, or a combination thereof.
8. The compound of claim 1 or a salt thereof, wherein the linker comprises an alkane, alkene, alkyne, cycloalkane, arylene, or imide.
9. The compound of claim 1 or a salt thereof, wherein the linker comprises an arylene.
10. The compound of claim 1 or a salt thereof, wherein the linker is covalently bound to B via an amide bond.
11. The compound of claim 1 or a salt thereof, wherein the linker is covalently bound to D via an amide bond.
12. A reconstitutable lyophilizate comprising a compound of claim 1 or a salt thereof.
13. The reconstitutable lyophilizate of claim 12 wherein the lyophilizate comprises a dose of the compound of claim 1 or a salt thereof.
14. A kit comprising the reconstitutable lyophilizate of claim 12 .