Drug-conjugates, conjugation methods, and uses thereof
View Patent ↗In one aspect, an active agent-conjugate, methods of preparing the active agent-conjugate, and uses thereof is provided.
1. An active agent-conjugate composition comprising Formula 1a:
or a pharmaceutically acceptable salt thereof,
wherein:
the A-component is an antibody or an antibody fragment comprising a heavy and light chain;
the E-component is selected from the group consisting of:
L 3 is an optionally substituted C 1 -C 6 alkyl, or L 3 is null, when L 3 is null the sulfur is directly connected to the E-component;
L 4 is an optionally substituted C 1 -C 6 alkyl, or L 4 is null, when L 4 is null the sulfur is directly connected to the E-component;
B is a monoclonal antibody or peptide;
each D is independently selected, wherein each D includes an active agent;
each L 2 is independently a linker, wherein L 2 links to E; and
n is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.
2. The active agent-conjugate of claim 1 , wherein L 3 is —(CH 2 )—; and L 4 is —(CH 2 )—.
3. The active agent-conjugate of claim 1 , wherein L 3 is null; and L 4 is null.
4. The active agent-conjugate of claim 1 , wherein:
is selected from the group consisting of:
5. The active agent-conjugate of claim 1 , wherein said active agent is independently selected from the group consisting of tubulin binders, DNA alkylators, DNA intercalators, enzyme inhibitors, and immune modulators.
6. The active agent-conjugate of claim 1 , wherein the structure of Formula Ia has a structure selected from the group consisting of:
7. The active agent-conjugate of claim 1 , wherein L 2 is a peptide or an oligosaccharide.
8. The active agent-conjugate of claim 1 , wherein the A component comprises at least one modified L-Alanine residue.
9. The active agent-conjugate of claim 1 , wherein said active agent is independently selected from peptides and nucleotides.
10. The active agent-conjugate of claim 1 , wherein L 2 is selected from the group consisting of —(CH 2 ) n —, —(CH 2 CH 2 O) n —, Val-Cit-PAB, Val-Ala-PAB, Val-Lys(Ac)-PAB, Phe-Lys-PAB, Phe-Lys(Ac)-PAB, D-Val-Leu-Lys, Gly-Gly-Arg, Ala-Ala-Asn-PAB, Ala-PAB, and PAB.