Discovery of 2-(Methylcarbonylamino) thiazole as PDE4 inhibitors via virtual screening and biological evaluation

doi:10.1016/j.jmgm.2023.108567

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	Discovery of 2-(Methylcarbonylamino) thiazole as PDE4 inhibitors via virtual screening and biological evaluation
	Ma,Rui; Song,Na; Wang,Lveli; Gu,Xi; Xiong,Feng; Zhang,Shuqun; Zhang,Jie; Yang,Weimin; Zuo,Zhili
	2023
发表期刊	JOURNAL OF MOLECULAR GRAPHICS & MODELLING
ISSN	1873-4243
卷号	124 页码:108567
摘要	Phosphodiesterase-4, the primary enzyme responsible for cAMP degradation in the majority of immune and inflammatory cells, plays a critical role in the regulation of intracellular cAMP levels. Consequently, small molecular entities capable of inhibiting PDE4 have been employed in the treatment of inflammation-associated disorders, such as chronic obstructive pulmonary disease (COPD), psoriasis, atopic dermatitis (AD), inflammatory bowel diseases (IBD), rheumatic arthritis (RA). In the present investigation, a multi-faceted approach was employed to identify novel PDE4 inhibitors, utilizing the co-crystallization structure of PDE4B available in the Protein Data Bank (PDB) database, drug-like screening, false positive filtration, similarity and ADMET screen, as well as molecular docking via multiple software platforms, in conjunction with bioactivity assays. A thiazol-3-propanamides derivative, designated MR9, was discovered to inhibit PDE4B activity with IC50 values of 2.12 & mu;M and suppress cellular inflammatory factor TNF-& alpha; release with an EC50 value of 3.587 & mu;M. These findings suggest that the innovative active scaffold of MR9 offers a promising foundation for further structural refinement aimed at developing more potent PDE4 inhibitors.
关键词	PHOSPHODIESTERASE-4 INHIBITOR ACCURATE DOCKING APREMILAST EFFICACY INSIGHTS DISEASE ASTHMA POTENT GLIDE
DOI	10.1016/j.jmgm.2023.108567
收录类别	SCI
WOS记录号	WOS:001050808100001
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/75454
专题	中国科学院昆明植物研究所
推荐引用方式 GB/T 7714	Ma,Rui,Song,Na,Wang,Lveli,et al. Discovery of 2-(Methylcarbonylamino) thiazole as PDE4 inhibitors via virtual screening and biological evaluation[J]. JOURNAL OF MOLECULAR GRAPHICS & MODELLING,2023,124:108567.
APA	Ma,Rui.,Song,Na.,Wang,Lveli.,Gu,Xi.,Xiong,Feng.,...&Zuo,Zhili.(2023).Discovery of 2-(Methylcarbonylamino) thiazole as PDE4 inhibitors via virtual screening and biological evaluation.JOURNAL OF MOLECULAR GRAPHICS & MODELLING,124,108567.
MLA	Ma,Rui,et al."Discovery of 2-(Methylcarbonylamino) thiazole as PDE4 inhibitors via virtual screening and biological evaluation".JOURNAL OF MOLECULAR GRAPHICS & MODELLING 124(2023):108567.

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