Author: Shen, Jun ; Zhang, Simeng ; Chen, Yadong ; Ning, Xiangzhen ; Zhang, Yanmin ; Liu, Yingxu ; Han, Weijie ; Xu, Chengcheng ; Liu, Haichun ; Fan, Qing

ABSTRACTIdentifying interactions between drugs and targets is crucial for drug discovery and development. Nevertheless, the determination of drug‐target binding affinities (DTAs) through traditional experimental methods is a time‐consuming process. Conventional approaches to predicting drug‐target interactions (DTIs) frequently prove inadequate due to an insufficient representation of drugs and targets, resulting in ineffective feature capture and questionable interpretability of results. To address these challenges, we introduce CGPDTA, a novel deep learning framework empowered by transfer learning, designed explicitly for the accurate prediction of DTAs. CGPDTA leverages the complementarity of drug–drug and protein–protein interaction knowledge through advanced drug and protein language models. It further enhances predictive capability and interpretability by incorporating molecular substructure graphs and protein pocket sequences to represent local features of drugs and targets effectively. Our findings demonstrate that CGPDTA not only outperforms existing methods in accuracy but also provides meaningful insights into the predictive process, marking a significant advancement in the field of drug discovery.

01 Dec 2024·Bioorganic Chemistry

Sodium cromoglycate exerts anti-pulmonary fibrosis effects by targeting the Keap1 protein to activate Nrf2 signaling

Article

Author: Huang, Yuwei ; Yuan, Lei ; Li, Yanchun ; Ma, Chao ; Wang, Chuncheng ; Liu, Xiaofeng ; Ma, Enlong ; Zhao, Xianchen ; Guan, Yingjun

Oxidative stress has been confirmed to be closely related to the occurrence and development of pulmonary fibrosis (PF). The Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid-2 related factor 2 (Nrf2) pathway plays a key role in maintaining cellular redox homeostasis. Targeting the Keap1 protein to activate Nrf2 could be a promising strategy for treating PF. Virtual screening via a pharmacophore model was used to screen candidate compounds with potential Keap1 binding ability from the U.S. Food and Drug Administration (FDA) database. The results revealed that sodium cromoglycate (Cro) has the highest fit value and absolute docking score and could improve the thermal stability of the Keap1 protein in a CETSA, confirming that Cro could bind to the Keap1 protein directly. Further studies revealed that Cro promoted Nrf2 translocation into the nucleus, relieved oxidative stress, prevented the epithelial-mesenchymal transition (EMT) process and upregulated fibrosis markers in TGF-β1-induced A549 cells, indicating that Cro has anti-pulmonary fibrosis activity in an in vitro lung fibrosis model. Moreover, in a mouse model of bleomycin (BLM)-induced pulmonary fibrosis, Cro administration improved pulmonary fibrosis, activated Nrf2 signaling, and blocked the EMT process. In summary, these results demonstrated that Cro could activate Nrf2 signaling to clear reactive oxygen species (ROS) by directly binding to Keap1 and alleviate pulmonary fibrosis by blocking the progression of EMT both in vitro and in vivo.

20 Sep 2024·Organic Letters

Nickel-Mediated Divergent Trifluoromethylation of Chlorinated and Brominated Phenol Derivatives through Chemoselective Cleavage of Ar–O and Ar–Cl(Br) Bonds

Article

Author: Chen, Xiang-Yi ; Qing, Feng-Ling ; Hu, Wei-Qiang

We report herein that nickel-mediated trifluoromethylation of chlorinated and brominated phenol derivatives ClArOTs and BrArOTf gave chloro(bromo)trifluoromethylarenes through the chemoselective cleavage of Ar-O bonds. Furthermore, under similar reaction conditions, the chemoselective trifluoromethylation of Ar-Cl and Ar-Br bonds of ClArOPiv and BrArOTs was achieved to give trifluoromethylated phenol derivatives.

100 Deals associated with Acemetacin

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KEGG	Wiki	ATC	Drug Bank
D01582	Acemetacin	M01AB11	DB13783

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Indication	Country/Location	Organization	Date
Bursitis	China	Foshan Huapusheng Pharmaceutical Co., Ltd.	01 Jan 1996
Pain	China	Foshan Huapusheng Pharmaceutical Co., Ltd.	01 Jan 1996
Tendinopathy	China	Foshan Huapusheng Pharmaceutical Co., Ltd.	01 Jan 1996
Osteoarthritis	Japan	Kowa Co., Ltd.	10 Jul 1992
Periarthritis	Japan	Kowa Co., Ltd.	10 Jul 1992
Low Back Pain	Japan	Kowa Co., Ltd.	16 Mar 1992
Musculoskeletal Diseases	Japan	Kowa Co., Ltd.	16 Mar 1992
Pain, Postoperative	Japan	Kowa Co., Ltd.	16 Mar 1992
Respiratory Tract Infections	Japan	Kowa Co., Ltd.	16 Mar 1992
Wounds and Injuries	Japan	Kowa Co., Ltd.	16 Mar 1992
Ankylosing Spondylitis	Germany	Meda Pharma GmbH	01 Jan 1980
Gout	Germany	Meda Pharma GmbH	01 Jan 1980
Joint Diseases	Germany	Meda Pharma GmbH	01 Jan 1980
Rheumatoid Arthritis	Germany	Meda Pharma GmbH	01 Jan 1980
Thrombophlebitis	Germany	Meda Pharma GmbH	01 Jan 1980

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