Cross-linkers and their uses
Charged or pro-charged cross-linking moieties and conjugates of cell binding agents and drugs comprising the charged or pro-charged cross-linking moieties and method of making the same.
1. A compound of formula (IV):
wherein:
Y′ represents a functional group that enables reaction with a cell-binding agent, wherein Y′ is N-hydroxysuccinimide ester;
D represents a cytotoxic drug linked to the cell-binding agent by a disulfide, thioether, thioester, peptide, hydrazone, ester, ether, carbamate, or amide bond;
one of R 1 , R 2 , R 3 , R 4 , R 9 , and R 10 is a charged substituent selected from SO 3 − or X-SO 3 , and the rest are H;
l and m are each 0;
n is 1; and
Z is absent.
2. The compound of claim 1 , wherein the cytotoxic drug is a maytansinoid.
3. The compound of claim 2 , wherein the cytotoxic drug is DM1 or DM4.
4. The compound of claim 2 , wherein the cytotoxic drug is DM4.
5. The compound of claim 1 , wherein D represents a maytansinoid drug linked to the cell-binding agent by a disulfide bond.
6. The compound of claim 5 , wherein the maytansinoid drug is DM1 or DM4.
7. The compound of claim 5 , wherein the maytansinoid drug is DM4.