다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

The analogs of nitrogen-based heterocycles occupy an exclusive position as a valuable source of therapeutic agents in medicinal chemistry. More than 75% of drugs approved by the FDA and currently available in the market are nitrogen-containing heterocyclic moieties. In the forthcoming decade, a much greater share of new nitrogen-based pharmaceuticals is anticipated. Many new nitrogen-based heterocycles have been designed. The number of novel N-heterocyclic moieties with significant physiological properties and promising applications in medicinal chemistry is ever-growing. In this review, we consolidate the recent advances on novel nitrogen-containing heterocycles and their distinct biological activities, reported over the past one year (2019 to early 2020). This review highlights the trends in the use of nitrogen-based moieties in drug design and the development of different potent and competent candidates against various diseases.

A Review on Recent Advances in Nitrogen-Containing Molecules and Their Biological Applications.

Medicinal attributes of 1,2,3-triazoles: Current developments

Anticancer targeted therapies are designed to exploit a particular vulnerability in the tumor, which in most cases results from its dependence on an oncogene and/or loss of a tumor suppressor. Genes in the phosphoinositide 3-kinase (PI3K)/AKT pathway are the most frequently altered in human cancers. Aberrant activation of this pathway, as a result of these somatic alterations, is associated with cellular transformation, tumorigenesis, cancer progression, and drug resistance. Several drugs targeting PI3K/ATK are currently in clinical trials, alone or in combination, in both solid tumors and hematologic malignancies. These drugs are the focus of this review.

Erratum: The PI3K/AKT Pathway as a Target for Cancer Treatment

Overcoming ABC transporter-mediated multidrug resistance: Molecular mechanisms and novel therapeutic drug strategies

Curriculum vitae of HDAC6 in solid tumors.

The invention discloses elastin-like polypeptides (ELP) for prokaryotic expression of fusion protein Prx by a non-digestion and non-chromatography purifying method and belongs to the field of genetic engineering. According to the elastin-like polypeptides, the type of the fourth amino acid in an elastin-like pentapeptide unit is changed and the elasticity function of the fourth amino acid is improved, and therefore, the reduction of the ELP length becomes possible. The ratio of K, V and F in the fourth basic group in the ELP pentapeptide unit is enabled to be 1: 6: 3. In terms of inteins, the high-efficiency intein gp41-1 is adopted; the C-terminal and the N-terminal of the intein are expressed separately, and the internal gene of the intein is mutated. The elastin-like polypeptides (ELPs) are ELP-IN and precursor protein ELP-IC-PrxI. The protein Prx is purified in a non-chromatography way by use of the elasticity function of the elastin-like polypeptides; no chromatographic column is required for separation, and the target protein precipitates by virtue of incubation at a certain temperature; besides, the precipitate can be re-dissolved in a buffer solution, and consequently, the protein can be purified more efficiently and quickly.

Elastin-like polypeptides (ELP) for prokaryotic expression of fusion protein Prx by non-digestion and non-chromatography purifying method

Cover Picture: Fabrication of Predominantly Mn4+‐Doped TiO2 Nanoparticles under Equilibrium Conditions and Their Application as Visible‐Light Photocatalyts (Chem. Asian J. 7/2014)

Background Cancer is one of the most serious diseases threatening human health with high morbidity and mortality in the world. For the treatment of cancer, chemotherapy is one of the most widely used strategies, for almost all kinds of tumors and diverse stages of tumor development. The efficacy of chemotherapy not only depends on the activity of the drug administrated but also on whether the compound could reach the effective therapeutic concentration in tumor cells. Therefore, expression and activity of drug-metabolizing enzymes (DMEs) in tumor tissues and metabolic organs of cancer patients are important for the dispositional behavior of anticancer drugs as well as the clinical response of chemotherapy. Methods This review summarizes the recent advancement of the DMEs expression and activity in various cancers, as well as the potential regulatory mechanisms of major DMEs in cancer and cancer therapy. Results Compared to normal tissues, expression and activity of major DMEs are significantly dysregulated in patients by various factors including epigenetic modification, ligand-activated transcriptional regulation and signaling pathways. Additionally, DMEs play an important role in anticancer drug efficacy, chemoresistance as well as the activation of prodrugs. Conclusion This review reinforces a more comprehensive understanding of DMEs in cancer and cancer therapy, and provides more opportunities for cancer therapy.

Role of Drug-metabolizing Enzymes in Cancer and Cancer Therapy.

Dual target compounds have become a hot spot in the treatment of cancer in recent years. Histone lysine specific demethylase 1 (LSD1) is identified as histone demethylase and acts as a key regulator involved in many other cellular activities through its demethylation function. We have reported a triazolo [1,5-α] pyrimidine-based DCN1(defective in cullin neddylation protein 1) inhibitor compound 383 (IC50 = 11 nM) which could selectively inhibit Cullin 3/1 neddylation in MGC-803 cells. In this research, we investigated that compound 383 could target LSD1 and inhibit the biological function of LSD1 in MGC-803 cells (IC50 = 0.53 μM). We found that compound 383 could induce the degradation of LSD1 and inhibit MGC-803 cell proliferation, migration and invasion in a dose-dependent manner. Compound 383 could cause cell cycle arrest at G2/M phase by down-regulating the expression of LSD1. In addition, compound 383 could significantly reverse epithelial-mesenchymal transition (EMT) through increase H3K4me methylation at E-cadherin promotor. Furthermore, the in vivo inhibitory effect of compound 383 without obvious toxicity was confirmed in nude mouse transplanted MGC-803 tumor cells model. Collectively, these results suggest that the DCN1 inhibitor compound 383 exhibits antiproliferative activity in gastric cancer cells by targeting LSD1 which promotes compound 383 as a good starting point for the development of dual-target therapeutics for gastric cancer. 

Yi-Chao Zheng

Papers

Curriculum vitae of HDAC6 in solid tumors.

Elastin-like polypeptides (ELP) for prokaryotic expression of fusion protein Prx by non-digestion and non-chromatography purifying method

Cover Picture: Fabrication of Predominantly Mn4+‐Doped TiO2 Nanoparticles under Equilibrium Conditions and Their Application as Visible‐Light Photocatalyts (Chem. Asian J. 7/2014)

Role of Drug-metabolizing Enzymes in Cancer and Cancer Therapy.

Discovery of the antitumor activities of a potent DCN1 inhibitor compound 383 targeting LSD1 in gastric cancer