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Receptor interacting protein 1 ( RIP1) kinase plays an important role in necroptosis, and inhibitors of the RIP1 kinase are thought to have a potential therapeutic value in the treatment of diseases related to necrosis. Herein, we report the structural optimization of a RIP1 kinase inhibitor, 1-(2,4-dichlorobenzyl)-3-nitro-1 H-pyrazole ( 1a). A number of 1-benzyl-1 H-pyrazole derivatives were synthesized and structure-activity relationship ( SAR) analysis led to the discovery of a potent compound, 4b, which showed a Kd value of 0.078 μ m against the RIP1 kinase and an EC50 value of 0.160 μ m in a cell necroptosis inhibitory assay. Compound 4b also displayed considerable ability to protect the pancreas in an l-arginine-induced pancreatitis mouse model. [ABSTRACT FROM AUTHOR]

As an invasive nuclear medical imaging technology, positron emission tomography (PET) possess the possibility to imaging the distribution as well as the density of selective receptors via specific PET tracers. Inspired by PET, the development of radio-chemistry has greatly promoted the progress of innovative imaging PET tracers for adenosine receptors, in particular adenosine A2A receptors (A2ARs). PET imaging of A2A receptors play import roles in the research of adenosine related disorders. Several radio-tracers for A2A receptors imaging have been evaluated in human studies. This paper reviews the recent research progress of PET tracers for A2A receptors imaging, and their applications in the diagnosis and treatment of related disease, such as cardiovascular diseases, autoimmune diseases, neurodegenerative and psychiatric disease. The future development of A2A PET tracers were also discussed. [ABSTRACT FROM AUTHOR]

As an invasive nuclear medical imaging technology, positron emission tomography (PET) possess the possibility to imaging the distribution as well as the density of selective receptors via specific PET tracers. Inspired by PET, the development of radio-chemistry has greatly promoted the progress of innovative imaging PET tracers for adenosine receptors, in particular adenosine A2A receptors (A 2A Rs). PET imaging of A2A receptors play import roles in the research of adenosine related disorders. Several radio-tracers for A 2A receptors imaging have been evaluated in human studies. This paper reviews the recent research progress of PET tracers for A2A receptors imaging, and their applications in the diagnosis and treatment of related disease, such as cardiovascular diseases, autoimmune diseases, neurodegenerative and psychiatric disease. The future development of A2A PET tracers were also discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Sun, Liu, Zhao and Wu.)

Objective: To synthesize and study the specific binding affinity of tumor-penetrating peptide YCCS to non-small cell lung carcinoma (NSCLC) cells in vitro., Methods: YCCS peptide was designed by fusing the neuropilin-1 (NRP-1) binding sequence and NSCLC binding peptide CS. YCCS peptide was synthesized and fluorescent labeled with N-terminal FITC. NRP-1 positive human NSCLC cell A549, NRP-1 positive human breast cancer cell MDA-MB-231, normal human bronchial epithelium HBE135-E6E7 and human liver cell HL-7702 were incubated respectively, then we observed the specific binding affinity of tumor-penetrating peptide YCCS to NSCLC cells., Results: After treated with 5 μmol/L peptide, significant fluorescent signals of FITC-YCCS peptide were demonstrated only in NSCLC A549 cells but marginal captured signal in MDA-MB-231, normal human HBE135-E6E7 or HL-7702 cells, which revealed specific NSCLC cells binding affinity. In 20 μmol/L treated group, non-specific binding were found in MDA-MB-231 and HL-7702 cells., Conclusion: The results of this novel designed YCCS peptide indicated a promising strategy for improving tumor penetrating with delivery capability of drugs to NSCLC A549 cells when treated with 5 μmol/L peptide.