China Pharmaceutical University

Zhengyu Jiang

Qidong You

Xiaoke Guo

Xiaoli Xu

Mengchen Lu

Jing Zhao

Lei Wang

Yan Wang

Dongdong Li

Xin Chen

Weilin Chen

Haopeng Sun

Yuting Liu

Xiaojin Zhang

Xian Zhang

Jun Xu

Yuhui Jin

Jing Gu

Hongli Shao

Zhiyun Chen

The present disclosure discloses a WDR5 protein-protein interaction inhibitor, including a compound having a structure represented by general formula (I). Experiments show that the inhibitor acts on a WDR5 protein and an interacting protein thereof including, but not limited to, MLL, selectively inhibits the proliferation of leukemia cells, and inhibits the methylation of H3K4 and the expression of downstream Hox/Meis-1 gene at the cellular level. The present disclosure also discloses a method for preparing the inhibitor and use thereof in the preparation of a drug for treating acute leukemia and other related diseases.

Aniline-based WDR5 protein-protein interaction inhibitor, and preparation method and use thereof

The present application relates to a hydrogen peroxide-responsive Keap1-Nrf2 PPI inhibitor prodrug, and a preparation method therefor. The hydrogen peroxide-responsive Keap1-Nrf2 PPI inhibitor prodrug pro2 has a chemical structure as shown below. By modifying a key carboxyl pharmacophore in a Keap1-Nrf2 inhibitor with a HO-responsive thiazolidinone moiety, a novel ROS-responsive antioxidant prodrug pro2 is synthesized. The HOactivated prodrug pro2 can simultaneously achieve targeted activation of Nrf2 and enhancement of therapeutic efficacy in the body. The prodrug is based on the concept of ROS activation-ROS clearance therapy, is the first example of a HO-responsive prodrug suitable for oral administration, and is expected to be used clinically by virtue of the characteristics of druggability and high targeting ability.

Hydrogen peroxide-responsive KEAP1-NRF2 ppi inhibitor prodrug, and preparation method therefor

Disclosed in the present invention are a naphthalenesulfonamide compound, a preparation method, and an application. The naphthalenesulfonamide compound provided by the present invention can interfere with Keap1-Nrf2 binding and activate Nrf2 to relieve inflammatory damage and improve an inflammatory microenvironment, has a potential anti-inflammatory activity, and can be used for preparing an anti-inflammatory drug for inflammatory damage of various inflammation-related diseases, including chronic obstructive pulmonary disease (COPD), Alzheimer's disease, Parkinson's disease, atherosclerosis, chronic kidney disease (CKD), diabetes, intestinal Inflammations, rheumatoid arthritis, etc.

Naphthalenesulfonamide compound, preparation method, and application

It discloses a proteolysis targeting chimeric molecule, a preparation method and an application thereof. The proteolysis targeting chimeric molecule provided by the disclosure can inhibit the expression of BCR-ABL and/or CRBN protein in BCR-ABL and/or CRBN positive leukemia K562 cells to varying degrees, and thus can be used to prepare drugs for treating BCR-ABL and/or CRBN positive leukemia, wherein the proteolysis targeting chimeric molecule with n=3 has excellent photo-isomerization activity, and can be used in preparation of the reagents or drugs for light-regulated degradation of BCR-ABL and/or CRBN protein. The disclosure also provides a method for synthesizing the series of proteolysis targeting chimeric molecules.

Proteolysis targeting chimeric molecule, preparation method, and application

Compounds of formula (I) having 1-sulfonamido-4-aryloxy as a basic backbone. A preliminary activity test showed that the compounds provide excellent interference of a binding of Nrf2 by Keap1, thereby activating Nrf2. The compounds have a potential anti-inflammatory activity and can be used to treat a plurality of inflammation-associated diseases, including chronic obstructive pulmonary disease (COPD), Alzheimer's disease, Parkinson's disease, atherosclerosis, chronic kidney disease (CKD), diabetes, gastroenteritis, rheumatoid arthritis, and the like. 

1-sulfonamido-4-aryloxy compounds, and preparation method and medicinal application thereof

Growing community of inventors

Nanjing, China

Zhengyu Jiang