Nrf2 activation of the antioxidant response element (ARE) is central to cytoprotective gene expression against oxidative and/or electrophilic stress. Unless activated by inflammatory, environmental, or oxidative stressors, Nrf2 is sequestered in the cytoplasm by its repressor, Keap1. Because of its protective capabilities, small molecules that activate Nrf2 signaling are being examined as potential anti-cancer or anti-inflammatory agents. DL-Sulforaphane N-acetyl-L-cysteine (SFN-NAC) is a major metabolite of SFN , a powerful inducer of chemopreventative enzymes via Keap1-Nrf2 signaling and ARE-driven gene expression. At 75 μM, SFN-NAC has been shown to increase ARE expression in HepG2-C8 cells. Its reported potency on ARE-related gene expression is roughly 8-fold less than SFN.
Cefminox (Sodium) is a new cephamycin antibiotic possessing a D-amino acid moiety derived from D-cysteine at the C-7B side chain. Cefminox is active against a wide range of bacteria, especially Gram-negative and anaerobic bacteria. Cefminox shows excellent in vivo efficacy (ED50) which is higher than would be expected from its in vitro activity (MIC). Moreover, cefminox possesses more potent activity in suppression of bacterial regrowth than other cephems[1]. Cefminox (Sodium) was the most active beta-lactam, with an MIC at which 50% of isolates are inhibited (MIC50) of 1.0 microg/ml and an MIC90 of 16.0 microg/ml. Cefminox was especially active against Bacteroides fragilis (MIC90, 2.0 microg/ml), Bacteroides thetaiotaomicron (MIC90, 4.0 microg/ml), fusobacteria (MIC90, 1.0 microg/ml), peptostreptococci (MIC90, 2.0 microg/ml), and clostridia, including Clostridium difficile (MIC90, 2.0 microg/ml)[2]. The use of a single preoperative dose of cefminox was similar in efficacy to 3 doses of cefoxitin administered every 4 hours, and that the serum and tissue concentrations attained provide adequate antibiotic coverage[3]. Moreover, cefminox as a dual agonist of IP (Prostacyclin receptor) and PPARγ (peroxisome proliferator-activated receptor-gamma) that significantly inhibits PASMC proliferation by up-regulation of PTEN (phosphatase and tensin homolog) and cAMP ( cyclic adenosine monophosphate), suggesting that it has potential for treatment of PAH(pulmonary arterial hypertension)[4].
Olmutinib is a novel third-generation epidermal growth factor receptor (EGFR) mutation-specific tyrosine kinase inhibitor, used in the treatment of T790M mutation positive non-small cell lung cancer. Olmutinib covalently binds a cysteine residue near the kinase domain of mutant EGFRs to prevent phosphorylation of the receptor. EGFRs are frequently over-expressed in lung cancer and contribute to activation of the phosphoinositide 3-kinase and mitogen-activated protein kinase pathways which both promote cell survival and proliferation. By inhibiting EGFR activation, Olmutinib attenuates the activation of these tumor-promoting pathways. In the first phase I II clinical study of Osimertinib, 800 mg day was chosen as the dose for subsequent studies, and the dose-limiting toxicity and maximum tolerated dose was not reached. Olmutinib received breakthrough therapy designation in the United States in December 2015 and was approved for use in Korea in May 2016.