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 having the formula B-L-IA, wherein
B is a ligand having the structure
wherein R is selected from the group consisting of —C(O)—, —CH 2 C(O)—, and —S— and R is the point of attachment to L,
L is a linker selected from the group consisting of ethylene-diamine, ethylene-diamine-glutamic acid, aminocaproyl-phenylalanine-phenylalanine-diaminopropionic acid-aspartic acid-cysteine, and a peptide of two or more amino acids, and
IA is an optical imaging agent selected from the group consisting of fluorescein, OREGON GREEN fluorescent agents, ALEXAFLUOR fluorescent agents, fluorescein, BODIPY fluorescent agents, rhodamine fluorescent agents, DYLIGHT fluorescent agents, IRDye 800CW, TEXAS RED, and phycoerythrin.
2. The compound of claim 1 , wherein L has a length of at least 7 atoms.
3. The compound of claim 1 , wherein L has a length of at least 10 Angstrom.
4. The compound of claim 1 , wherein the OREGON GREEN fluorescent agent selected from the group consisting of OREGON GREEN 488 and OREGON GREEN 514.
5. The compound of claim 1 , wherein the ALEXAFLUOR fluorescent agent selected from the group consisting of ALEXAFLUOR 488 and ALEXAFLUOR 647.
6. The compound of claim 1 , wherein the BODIPY fluorescent age selected from the group consisting of BODIPY F1 and BODIPY 505.
7. The compound of claim 1 , wherein the rhodamine fluorescent agent is tetramethylrhodamine.
8. The compound of claim 1 , wherein the DYLIGHT fluorescent agent is DYLIGHT 680.
9. The compound of claim 1 , wherein the compound is capable of or adapted to fluoresce after distribution thereof in tissue.
10. The compound of claim 9 , wherein the tissue is a tumor or a lymph node.
11. The compound of claim 1 wherein the compound is selective for targeting to a tumor cell.
12. A composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier, excipient or diluent.