Proteases are now seen as extremely important signaling molecules, which have a critical role in a number of essential physiological processes, including pathological ones. An overview of guidelines on how to develop protease inhibitors. Many drugs based on enzyme inhibition are described, including the ACE inhibitors, which regulat blood pressure. New protease inhibitors, which are still in clinical or preclinical development are also described. Definitely a new and original view on this area, which is of major importance for the development of new drugs. Cited 85 times since September 2006.
COBISS.SI-ID: 20086311
It has been demonstrated that the increased cysteine cathepsins activity is associated with angiogenic vasculature and invasive fronts of carcinomas during tumorigenesis in transgenic mouse models using activity-based chemical probes and in vivo imaging. A broad-spectrum epoxide type cysteine cathepsin inhibitor JPM-OEt was shown to effectively block several stages of tumorigenesis in the RIP1-Tag2 transgenic mouse model, offering new therapeutic opportunities in cancer treatment. This is a preview paper by invitation to the first author. Cited 40 times.
COBISS.SI-ID: 18246695
In this work we have demonstrated that selective lysosome disruption in a cellular model (HeLa) can induce apoptosis through the release of cysteine cathepsins to the cytosol and subsequent caspase activation. Bid was shown to be the target for cysteine cathepsins in this cellular model. We have further shown that multiple cathepsins can cleave Bid in vitro and induce cytochrome c release from mitochondria. This work is thus a major contribution towards understanding of the molecular mechanism of lysosomal pathways to apoptosis. Cited 128 times
COBISS.SI-ID: 18033959
Selective cell permeable activity-based probes for detection of cysteine cathepsins in cellular systems were developed by the so-called reverse-design from the existing optimized compounds in preclinical development. This offers an enormous advantage over existing probes, as such compounds have been already optimized for in vivo use. It also provides excellent basis for future work in drug discovery, focusing on in vivo imaging of proteases in various diseases such as cancer, osteoporosis and inflammatory diseases with a further goal to identify new targets and/or to monitor disease treatment.
COBISS.SI-ID: 21274663
This paper got a mark "must read" by Faculty of 1000 Biology indicating importance for a new hypothesis, new finding and a novel drug target. (http://www.f1000biology.com/article/id/1100052/evaluation)
COBISS.SI-ID: 21275175