Hans-Georg LERCHEN,Anne-Sophie REBSTOCK,Leo MARX,Sarah Anna Liesa JOHANNES,Beatrix STELTE-LUDWIG,Lisa DIETZ,Hannah JOERISSEN,Christoph MAHLERT,Simone GREVEN,Anette SOMMER
申请号：
US16472634
公开号：
US20190351066A1
申请日:
2017.12.18
申请国别(地区):
US
年份:
2019
代理人:
摘要：
The invention relates to novel prodrugs or conjugates of the general formula (Ia)in which La, n, R and D have the definitions given in the description and which have a structural motif reduced to an asparagine derivative as cleavage site for tumour-associated proteases such as legumain, in which cytotoxic drugs, for example kinesin spindle protein inhibitors, are released by legumain cleavage, and to the use of these prodrugs or conjugates for treatment and/or prevention of diseases, and to the use of these prodrugs or conjugates for production of medicaments for treatment and/or prevention of diseases, especially of hyperproliferative and/or angiogenic disorders, for example cancers. Reduction of the legumain-cleavable substrate peptide sequence to an asparagine derivative as structural motif, as a result of slowed legumain cleavage, achieves an increase in stability in the lysosomes of healthy organs while simultaneously maintaining the high anti-tumour effect.
