1. Benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone (Z-VAD.FMK) inhibits apoptosis by blocking the processing of CPP32
E A Slee, H Zhu, S C Chow, M MacFarlane, D W Nicholson, G M Cohen Biochem J. 1996 Apr 1;315 ( Pt 1)(Pt 1):21-4. doi: 10.1042/bj3150021.
Interleukin-1 beta converting enzyme (ICE)-like proteases, which are synthesized as inactive precursors, play a key role in the induction of apoptosis. We now demonstrate that benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone (Z-VAD.FMK), an ICE-like protease inhibitor, inhibits apoptosis by preventing the processing of CPP32 to its active form. These results suggest that novel inhibitors of apoptosis can be developed which prevent processing of proforms of ICE-like proteases.
2. Caspase-3 inhibitor inhibits enterovirus D68 production
Wenbo Huo, et al. J Microbiol. 2020 Sep;58(9):812-820. doi: 10.1007/s12275-020-0241-y. Epub 2020 Sep 1.
Enterovirus D68 (EVD68) is an emerging pathogen that recently caused a large worldwide outbreak of severe respiratory disease in children. However, the relationship between EVD68 and host cells remains unclear. Caspases are involved in cell death, immune response, and even viral production. We found that caspase-3 was activated during EVD68 replication to induce apoptosis. Caspase-3 inhibitor (Z-DEVD-FMK) inhibited viral production, protected host cells from the cytopathic effects of EVD68 infection, and prevented EVD68 from regulating the host cell cycle at G0/G1. Meanwhile, caspase-3 activator (PAC-1) increased EVD68 production. EVD68 infection therefore activates caspase-3 for virus production. This knowledge provides a potential direction for the prevention and treatment of disease related to EVD68.
3. PET Radiopharmaceuticals for Personalized Medicine
Sushil Sharma Curr Drug Targets. 2016;17(16):1894-1907. doi: 10.2174/1389450117666160720091233.
Recent advances in the self-shielded cyclotrons, improved targets, videomonitored hot cells design, and automated PET radiopharmaceutical (RPs) synthesis modules, utilizing computer-controlled graphic user interphase (GUI) has revolutionized PET molecular imaging technology for basic biomedical research and theranostics to accomplish the ultimate goal of evidence-based personalized medicine. Particularly, [18F]HX4: (3-[18F]fluoro-2-(4-((2-nitro-1Himidazol-1-yl)methyl)-1H-1,2,3,-triazol-1- yl)-propan-1-ol), 18F-FAZA: 1-(5-[18F]Fluoro-5-deoxy-α-D-arabinofuranosyl)-2- nitroimidazole, and 18F-FMSIO: 18F-Ffluoromisonidazole to assess tumor hypoxia, [18F]FB-VAD-FMK: [18F]4-fluorobenzylcarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone to determine in vivo apoptosis, 64Cu-PTSM: 64Cu-Pyrualdehyde Bis-NMethylthiosemicarbazone for brain and myocardial perfusion imaging, and 68Ga-DOTATOC: 68Ga- DOTAD-Phy1-Tyr3-octreotide and 68Ga-DOTANOC: 68Ga-(1,4,7,10-tetraazacyclododecane- N,N',N'',N'''-tetraacetic acid)-1-NaI3-octreotide for neuroendocrine and neural crest tumors have demonstrated great promise in personalized theranostics. Furthermore, multimodality imaging with 124IPET/ CT and 18FDG-PET/CT rationalizes 131I treatment in thyroid cancer patients to prevent cost and morbid toxicity. In addition to 18F-labeled PET-RPs used in clinical practice, novel discoveries of chemical reactions including transition metal-mediated cross-coupling of carbon-carbon, carbonheterocarbon, and click chemistry at ambient temperature with significantly reduced synthesis times, labeled even with short-lived radionuclides such as 11C, has facilitated development of novel PET-RPs. These innovative approaches to synthesize PET-RPs and efficient image acquisition capabilities have improved the resolution of multimodality imaging and significantly reduced the radiation exposure to patients as well as healthcare professionals. Future developments in novel PET-RPs, utilizing automated microfluidic synthesis modules and multifunctional nanoparticles, will improve biomarker discovery, internal dosimetry, pharmacokinetics, immunotherapy, and stem cell tracking in regenerative medicine. This review provides recent developments in the synthesis of clinically-significant cyclotron and generator- based PET-RPs with potential applications in cardiovascular diseases, neurodegenerative diseases, and cancer to accomplish the ultimate goal of evidence-based personalized theranostics.
