Synthesis,pharmacokinetics and in vivo antifungal activity of the novel water-soluble prodrugs of itraconazole analogue YL-24

改进 itraconazole 类似物的水的溶解度，化合物 1 (YL-24 ) ，一系列新奇 prodrugs 被综合。在这些 prodrugs 之中，磷酸盐 disodium 盐混合物在在缓冲区答案的在中立附近的 pH 和足够的稳定性的 7 展出优秀水的溶解度(9.8 mg/mL ) ，与有利 pharmacokinetic 侧面一起。特别地，在鼠科的全身的 Candida albicans SC5314 感染模型加重 1 和 7 提供的中等幸存功效，但是他们的功效比 fluconazole 的弱。

Drug discovery and development targeting the life cycle of SARS-CoV-2

A newly emerged coronavirus,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),belongs to the/β-coronavirus family and shows high similarities with SARS-CoV.O n March 11,2020,the World Health Organization(WHO)declared SARS-CoV-2 a global pandemic,and the disease was named the coronavirus disease 2019(COVID-19).The ongoing COVID-19 pandemic has caused over 46 million infections and over one million deaths worldwide,and the numbers are still increasing.Efficacious antiviral agents are urgently needed to combat this virus.The life cycle of SARS-CoV-2 mainly includes the viral attachment,membrane fusion,genomic replication,assembly and budding of virions.Accordingly,drug development against SARS-CoV-2 currently focuses on blocking spike protein binding to ACE2,inhibiting viral membrane fusion with host cells,and preventing the viral replication by targeting 3C-Iike protease,papain-like protease,RNA-dependent R N A polymerase as well as some host-cell proteins.In this review,the advances of drug development in these three major areas are elaborated.

Enantiomers of Ohmefentanyl and Its Analgesic Activity

Since the existence of multiple opioid receptors was first proposed by Martin,this concept was subsequently substantiated by the pharmacological tests and receptor binding assays.Now three subclasses of opioid receptor have gained

RNA Methylation m6A:A New Code and Drug Target?

The m^6A-RNA modification is a dynamic and reversible process,which has emerged as a new RNA code for the regulation of gene expression.The functional network of methyltransferases(writers),demethylases(erasers),and binding proteins(readers)modulate the level of m^6A modification.Dysfunction of RNA methylation has been associated with various fundamental biological processes and human diseases.Herein,we briefly introduce an understanding-enabled manipulation on m^6A RNA modification with an emphasis on the use of small-molecule intervention.

GPR160 is a potential biomarker associated with prostate cancer

Dear Editor,Prostate cancer(PC)is one of the most common noncutaneous cancers among men worldwide with a relatively higher incidence and mortality rate.1 Conventional screening for prostate cancer relies on prostate-specific antigen(PSA),a valuable biomarker but has some deficiencies.Radical prostatectomy,androgen ablation,and radiotherapy are still commonly used treatments for localized prostate cancer.

PBKα inhibitor impairs AKT phosphorylation and synergizes with novel angiogenesis inhibitor AL3810 in human hepatocellular carcinoma

Dear Editor,Hepatocellular carcinoma(HCC)is the second leading cause of cancer-related death worldwide with a 5-year survival rate-50-80% after curative treatment,like surgery,targeted therapy plus TACE or RFA or local treatments,immunotherapy,and so on.1 The approval of several angiogenesis inhibitors,such as sorafenib,regorafenib,lenvatinib,and cabozantinib,have shown therapeutic potential for HCC treatment.However,the improvement of overall survival or progression-free survival is still limited based on angiogenesis inhibitor monotherapy at present.

ACE2-Targeting antibody suppresses SARS-CoY-2 Omicron and Delta variants

Dear Editor,The pandemic of COVID-19 continues worldwide with many variants arising,especially SARS-CoV-2 Delta(B.1.617.2)and Omicron(B.1.1.529)variants of concern(VOCs).According to WHO,Omicron has spread in almost all the countries with a doubling time less than Delta VOC.