This technology is for fast acting molecular probes made from a fluorescent quencher molecule, a fluorophore, an enzyme cleavable oligopeptide (for example targeted by protease) and FDA-approved polyethylene glycol (PEG) as well as associated methods to identify cell activity with these probes. Proteases regulate many cell processes such as inflammation as well as pathological processes in cancer and cardiovascular disease. High protease activity is associated with metastatic cancers. Proteases are also active in apoptosis, and tissue remodeling in cardiovascular disease. Although highly useful in vitro, conventional probes are unstable, nonspecific or slow activating in vivo. This new probe is faster than standard probes (30 min vs. 24 hrs) and has enhanced target-to background ratios. It enables quick screening of animals in an array of applications related to protease-associated diseases and other diseases. It may detect specific biological targets and monitor in vivo therapeutic efficacy in real time. Most drug candidates identified by in vitro screening fail in vivo. Failures are costly. Identifying in vivo drug efficacy sooner would reduce waste and increase successful drug development.