ABSTRACT
Compared with the traditional anti-tumor therapy,the antibody-based therapeutic strategies have shown consider?ably higher targeting selectivity and lower side effects. Antibody drug conjugates(ADC),combining the advantage of the biological antibodies and small molecule toxins,is regarded as a new way for the future cancer therapy. Maytansines are one of the cytotoxins widely used in ADC and the postmarketing ADC ado-trastuzumab emtansine(Kadcyla,ATE)which use such toxins successfully has expanded the indications from leukemia to other solid tumors. Currently,the clinical research progress in such ADC goes smoothly. This paper reviews the characteristics,metabolic characteristics,preparation of each component and the latest clinical research prog?ress in the maytansine class ADC.
ABSTRACT
Antibody drug conjugates(ADC) are a novel biological targeted anti-cancer agents that have the specificity target of monoclonal antibody and the significant cytotoxicity of the drug. It can not only improve the curative effect of the antibody but also expand the scope of clinical application of the small molecule toxins. Auristatins have been widely used in ADC and has achieved great success because of their powerful biological activity. The structure feature of auristatins is different from that of other cytotoxins , which determine the design of this kind of ADC′ linker is different from others′. We review the progress in each component and the latest clinical research of the auristatin class ADC, which may benefit to the further development of ADC.
ABSTRACT
A series of phthalazine ketone compounds were synthesized and the structures were confirmed by H NMR and HR-MS spectrum. All target compounds were obtained through 7 steps, including selective reduction, nitration, bromination, ring enlargement, reduction, Knoevenagel and acylated reaction. The compounds were evaluated for their immunosuppressive effects of T-cell proliferation and inhibitory activity of IMPDH type II in vitro, as well as their structure-activity relationship were assessed. Several compounds exhibited strong immunosuppressive properties, especially compounds 7f and 7h, with IC50 values of 0.093 micromol x L(-1) and 0.14 micromol x L(-1) respectively, which were superior to mycophenolic acid. The information obtained from the studies may be useful for further research on the immunosuppressive agents.