Dual acting prodrugs
A prodrug is provided which includes at least two different pharmaceutically and/or diagnostically active compounds independently bound by cleavable linkers and a protein-binding moiety which is capable of binding to carrier a molecule.
1. A prodrug comprising
(i) at least a first pharmaceutically and/or diagnostically active compound, the first pharmaceutically and/or diagnostically active compound is a cytokine;
(ii) at least a second pharmaceutically and/or diagnostically active compound;
(iii) two or more cleavable linkers; and
(iv) a protein-binding moiety, the protein-binding moiety is a maleinimide group that binds in situ to cysteine-34 of albumin;
wherein the first and the second pharmaceutically and/or diagnostically active compounds are each bound to a cleavable linker,
wherein the first and the second pharmaceutically and/or diagnostically active compounds are different from each other, and
wherein the two or more cleavable linkers can independently be cleaved hydrolytically and/or enzymatically and/or pH-dependently.
2. The prodrug according to claim 1 , wherein the second pharmaceutically and/or diagnostically active compound is selected from the group consisting of a cytostatic agent, a cytokine, an immunosuppressant, an antirheumatic, an antiphlogistic, an antibiotic, an analgesic, a virostatic, or an antimycotic agent, a transcription factor inhibitor, a cell cycle modulator, a multidrug resistance (MDR) modulator, a proteasome or protease inhibitor, an apoptosis modulator, an enzyme inhibitor, an angiogenesis inhibitor, a hormone or hormone derivative, a radioactive substance, a light emitting substance, or a light absorbing substance.
3. The prodrug according to claim 1 , wherein the cleavable linker is a p-aminobenzyloxycarbonyl (PABC) linker.
4. A pharmaceutical composition comprising the prodrug according to claim 1 , and optionally a pharmaceutically acceptable carrier and/or a pharmaceutically acceptable adjuvent and/or a diluent.