1.Clinical trial investigators′ satisfaction with clinical research coordinators and discussion on managing strategy
Xin WANG ; Huiqing YAO ; Li LIU ; Xuening LI ; Haijuan ZHAO ; Kexin ZHANG ; Yuantai DU
Chinese Journal of Hospital Administration 2018;34(7):604-608
Objective To learn the investigators′ satisfaction with CRCs and to identify the shortcomings with the CRC industry or institutional management for improvement. Methods A questionnaire survey was conducted among 120 clinical trial investigators at three tertiary general hospitals in January 2018. The questionnaire covered the basics, satisfaction with CRC, and comments of the investigator on other works of the CRC. The data acquired were subject to descriptive analysis, and the count data comparison method was Fisher precise test. Results The investigators were satisfied with CRCs in general. Specifically, their satisfaction with the " sense of responsibility" , " work hours" , and " command of GCP protocols"ranged 72.6% to 83.2% . That with " initiative" , " work stability" , and " rich clinical trial experience" fell below 60.0%. Affiliation of CRCs was correlated to "initiative"(P=0.007), and "command of clinical trial schemes and trial procedures" ( P =0.043), while investigators′ satisfaction with CRCs of uncertain affiliation fell significantly. Investigators′ experience was correlated to the " command of GCP protocols" of CRCs(P=0.035 ), as the more experienced the investigator, the less their satisfaction with the CRC. Conclusions Hospitals are expected to build a CRC standardized training system and hierarchical certification system; to standardize their CRC recruitment mechanism for overall management; to enhance their budgeting capability for sufficient CRC expenses, higher investigator efficiency and assured clinical trial quality.
2.Novel PF74-like small molecules targeting the HIV-1 capsid protein: Balance of potency and metabolic stability.
Lei WANG ; Mary C CASEY ; Sanjeev Kumar V VERNEKAR ; Rajkumar Lalji SAHANI ; Karen A KIRBY ; Haijuan DU ; Huanchun ZHANG ; Philip R TEDBURY ; Jiashu XIE ; Stefan G SARAFIANOS ; Zhengqiang WANG
Acta Pharmaceutica Sinica B 2021;11(3):810-822
Of all known small molecules targeting human immunodeficiency virus (HIV) capsid protein (CA), PF74 represents by far the best characterized chemotype, due to its ability to confer antiviral phenotypes in both early and late phases of viral replication. However, the prohibitively low metabolic stability renders PF74 a poor antiviral lead. We report herein our medicinal chemistry efforts toward identifying novel and metabolically stable small molecules targeting the PF74 binding site. Specifically, we replaced the inter-domain-interacting, electron-rich indole ring of PF74 with less electron-rich isosteres, including imidazolidine-2,4-dione, pyrimidine-2,4-dione, and benzamide, and identified four potent antiviral compounds (