Advances in cGAS-STING pathway and its inhibitors in immune and inflammatory diseases / 中国药理学通报

The cGAS-STING signaling pathway is one of the main pathways of immune defense against many types of pathogens. cGAS catalyzes the production of the second messenger cGAMP (cyclic GMP-tVMP) by recognizing plasma DNA and cGAMP subsequently binds to the interferon gene stimulating factor (STING). The pathway induces the production of type I interferon (IFN-I) and activates the innate immune system. The activation of the cGAS-STI]NG pathway could facilitate self-protection,thus STI]NG agonists for tumor immunotherapy have attracted much attention in recent years,and several drug candidates have been in clinical trials. Meanwhile,aberrant activation of cGAS-STI]NG could lead to autoimmune diseases and has attracted extensive interest in developing its inhibitors. This paper summarizes the mechanism and regulatory sites of the cGAS-STI]NG pathway,and outlines the research progress of cGAS-STING pathway-related immune and inflammatory diseases and its inhibitors.

Design and synthesis of quinoxaline derivatives and their antitumor activities / 药学学报

<p><b>AIM</b>To design and synthesize novel quinoxaline derivatives as antitumor agents.</p><p><b>METHODS</b>Using 4-chloro-2-nitroaniline as a starting compound, followed by substitution, reductive cyclization, oxidation, and chlorination, to give the key intermediate 2,7-dichloroquinoxaline (7), which reacted with different phenolic compounds to afford quinoxaline derivatives.</p><p><b>RESULTS</b>The structures of the target molecules were characterized by elemental analysis, 1H NMR, MS, and IR.</p><p><b>CONCLUSION</b>At concentration of 1 x 10(-4) mol x L(-1), some of the derivatives showed equal antitumor activities to XK469.</p>

Synthesis and pharmacology of 8-amino-3-(tetrahydro-2-furanyl)methyl benzomorphan / 药学学报

<p><b>AIM</b>To design and synthesize new chiral 8-(substituted) amino-analogues of 3-[(tetrahydro-2-furanyl)methyl] benzomorphans, to expand knowledge of the structure-activity relationship (SAR) for 8-aminobenzomorphan.</p><p><b>METHODS</b>Target compounds were synthesized from the 8-triflate of the optically active 3-[(tetrahydro-2-furanyl)methyl]-2,6-methano-benzomorphans using Pd-catalyzed aminations. Opioid receptor binding experiments were performed to evaluate their biological activities.</p><p><b>RESULTS</b>Both 8-amino and 8-phenylamino analogues showed lower binding affinity for mu, delta and kappa receptors than corresponding 8-hydroxy-3-[(tetrahydro-2-furanyl)methyl]-2,6-methano-benzomorphan in vitro.</p><p><b>CONCLUSION</b>The relative poor binding affinity of the target compounds did not warrant conducting the in vivo studies to determine if they have the profile(kappa agonist/mu antagonist) that will be potentially useful in the treatment of drug addiction. Further study is in progress.</p>