Deciphering Nonbioavailable Substructures Improves the Bioavailability of Antidepressants by Serotonin Transporter

Wang, Zhi-Zheng; Yi, Chao; Huang, Jun-Jie; Xu, Tengfei; Chen, Kang-Zhi; Wang, Zusheng; Xue, Ya‐Ping; Lu, Jielian; Nie, Biao; Zhang, Yingjun; Jin, Chuanfei; Hao, Ge‐Fei

doi:10.1021/acs.jmedchem.2c01339

Cited by 3 publications

(2 citation statements)

References 63 publications

(108 reference statements)

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“…To design novel anti-depressants with improved bioavailability, Wang et al. performed SERT-based drug design with the aid of ACFIS 2.0 (Figure 4C ) ( 48 ). The crystal structure of the vilazodone-SERT complex (PDB ID: 7lwd) was uploaded to launch a CORE_GEN operation.…”

Section: Resultsmentioning

confidence: 99%

ACFIS 2.0: an improved web-server for fragment-based drug discovery via a dynamic screening strategy

Shi

Wang

et al. 2023

Nucleic Acids Research

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Drug discovery, which plays a vital role in maintaining human health, is a persistent challenge. Fragment-based drug discovery (FBDD) is one of the strategies for the discovery of novel candidate compounds. Computational tools in FBDD could help to identify potential drug leads in a cost-efficient and time-saving manner. The Auto Core Fragment in silico Screening (ACFIS) server is a well-established and effective online tool for FBDD. However, the accurate prediction of protein-fragment binding mode and affinity is still a major challenge for FBDD due to weak binding affinity. Here, we present an updated version (ACFIS 2.0), that incorporates a dynamic fragment growing strategy to consider protein flexibility. The major improvements of ACFIS 2.0 include (i) increased accuracy of hit compound identification (from 75.4% to 88.5% using the same test set), (ii) improved rationality of the protein-fragment binding mode, (iii) increased structural diversity due to expanded fragment libraries and (iv) inclusion of more comprehensive functionality for predicting molecular properties. Three successful cases of drug lead discovery using ACFIS 2.0 are described, including drugs leads to treat Parkinson's disease, cancer, and major depressive disorder. These cases demonstrate the utility of this web-based server. ACFIS 2.0 is freely available at http://chemyang.ccnu.edu.cn/ccb/server/ACFIS2/.

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Section: Resultsmentioning

confidence: 99%

ACFIS 2.0: an improved web-server for fragment-based drug discovery via a dynamic screening strategy

Shi

Wang

et al. 2023

Nucleic Acids Research

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“…Especially, serotonin receptor, HTR1A, is known to regulate serotonin signaling in the central nervous system and is reported to have a critical role in depression by reducing serotonin secretion and activation [4]. As such, selective serotonin reuptake inhibitors have been widely used in clinical practice for anti-depression medicine [5].…”

Section: Introductionmentioning

confidence: 99%

Physical Activity and Depression: Nationwide Evaluation of Depression and Physical Activity in South Korea

Kim,

Yoon

2024

Exerc Sci

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PURPOSE: The relationship between depression and physical activity levels in adults in Korea was determined using data from the National Health and Nutrition Survey (K-NAESE).METHODS: Data collected from K-NAESE between 2014 and 2020, comprising 29,716 (male: 13,416, female: 16,300) participants, were analyzed using a complex sample statistical analysis by applying differential weight to the variables to analyze the relationship between depression and physical activity levels in an estimated South Korean population (50,881,242). Demographic factors were used as control variables while constructing an independent variable-by-variable fit model for the zero-inflated Poison Regression analysis of PHQ-9 depression scores, and a meaningfully interpretable fit model was used in the final model.RESULTS: A significant relationship was observed between the total PHQ-9 score and commute physical activity (OR = 1.042; SE, 0.006; p < .001) and moderate-intensity leisure and physical activity time (OR = 1.116; SE, 0.008; p < .001). A significant association was found between the PHQ-9 scores and physical factors (grip strength; OR = 0.985; SE, 0.001; p < .001). Using Binomial Logistic Model for Depression Classification, a significant association was observed for classification as low/high-risk depression in individuals without moderate-intensity physical activity (OR = 1.190; SE, 0.046; p < .001). Furthermore, individuals with a high grip strength were classified as low/high-risk depression compared to a normal grip strength (OR = 0.980; SE, 0.004; p < .001).CONCLUSIONS: These findings indicate that a negative association exists between depression and the availability of moderate-intensity leisure and structured physical activity. Furthermore, a negative association was also found between depression and grip strength in the general population of South Korea aged in individuals over the age of 18.

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Greed

2023

Nat Rev Chem

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Deciphering Nonbioavailable Substructures Improves the Bioavailability of Antidepressants by Serotonin Transporter

Cited by 3 publications

References 63 publications

ACFIS 2.0: an improved web-server for fragment-based drug discovery via a dynamic screening strategy

ACFIS 2.0: an improved web-server for fragment-based drug discovery via a dynamic screening strategy

Physical Activity and Depression: Nationwide Evaluation of Depression and Physical Activity in South Korea

Sorry, this item is not (bio)available

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