SARS-CoV-2:structure,host,virus source and pathogenesis

Cancer is a serious threat to human life and a big problem in clinical treatment.Some natural active substances extracted from Traditional Chinese Medicine can effectively inhibit the growth of cancer cells,which is a new direction for finding more effective anticancer drugs.Osthole is a natural coumarin compound extracted from Traditional Chinese Medicines such as Cnidium monnieri,Angelica pubescens and Peucedanum praeruptorum Dunn.It has significant inhibitory activity against a variety of cancers.This paper summarizes the anticancer effects and molecular mechanisms of osthole in the treatment of cancers in recent years in order to provide references for further research.

The regulatory mechanisms and inhibitors of isocitrate dehydrogenase 1 in cancer

Reprogramming of energy metabolism is one of the basic characteristics of cancer and has been proved to be an important cancer treatment strategy.Isocitrate dehydrogenases(IDHs)are a class of key proteins in energy metabolism,including IDH1,IDH2,and IDH3,which are involved in the oxidative decarboxylation of isocitrate to yield a-ketoglutarate(a-KG).Mutants of IDH1 or IDH2 can produce D-2-hydroxyglutarate(D-2HG)with a-KG as the substrate,and then mediate the occurrence and development of cancer.At present,no IDH3 mutation has been reported.The results of pan-cancer research showed that IDH1 has a higher mutation frequency and involves more cancer types than IDH2,implying IDH1 as a promising anti-cancer target.Therefore,in this review,we summarized the regulatory mechanisms of IDH1 on cancer from four aspects:metabolic reprogramming,epigenetics,immune microenvironment,and phenotypic changes,which will provide guidance for the understanding of IDH1 and exploring leading-edge targeted treatment strategies.In addition,we also reviewed available IDH1 inhibitors so far.The detailed clinical trial results and diverse structures of preclinical candidates illustrated here will provide a deep insight into the research for the treatment of IDH1-related cancers.

Arf6 as a therapeutic target:Structure,mechanism,and inhibitors

ADP-ribosylation factor 6(Arf6),a small G-protein of the Ras superfamily,plays pivotal roles in multiple cellular events,including exocytosis,endocytosis,actin remodeling,plasma membrane reorganization and vesicular transport.Arf6 regulates the progression of cancer through the activation of cell motility and invasion.Aberrant Arf6 activation is a potential therapeutic target.This review aims to understand the comprehensive function of Arf6 for future cancer therapy.The Arf6 GEFs,protein structure,and roles in cancer have been summarized.Comprehending the mechanism underlying Arf6-mediated cancer cell growth and survival is essential.The structural features of Arf6 and its efforts are discussed and may be contributed to the discovery of future novel protein-protein interaction inhibitors.In addition,Arf6 inhibitors and mechanism of action are listed in the table.This review further emphasizes the crucial roles in drug resistance and attempts to offer an outlook of Arf6 in cancer therapy.

PROTAC technology as a novel tool to identify the target of lathyrane diterpenoids

To the Editor:Proteolysis Targeting Chimera(PROTAC)is an emerging approach to selectively degrading target proteins by utilizing endogenous proteasome.Since PROTACs can degrade target proteins without high affinity,it is natural to speculate that this technology can be used to identify the targets of natural products。Although a recent study reported the employment of PROTACs to explore the unknown non-kinase target of a multi-kinase inhibitor sorafenib,whether PROTACs can be used to find the potential targets of natural products remains unexplored.