Design and synthesis of novel benzoic acid derivatives as striatal-enriched protein tyrosine phosphatase (STEP) inhibitors with neuroprotective properties.

As a central nervous system-specific member of the protein tyrosine phosphatase (PTP) family, the striatal-enriched protein tyrosine phosphatase (STEP) is an attractive drug target for neurodegenerative diseases. Here, we reported the discovery of a series of benzoic acid derivatives as new STEP inhibitors. Among them, compound 14b exhibited good STEP inhibitory activity and displayed selectivity against other PTPs.

Learn2Talk: 3D Talking Face Learns From 2D Talking Face.

The speech-driven facial animation technology is generally categorized into two main types: 3D and 2D talking face. Both of these have garnered considerable research attention in recent years. However, to our knowledge, the research into 3D talking face has not progressed as deeply as that of 2D talking face, particularly in terms of lip-sync and perceptual mouth movements.

Pharmacologic activation of activating transcription factor 6 contributes to neuronal survival after spinal cord injury in mice.

The impact of primary and secondary injuries of spinal cord injury (SCI) results in the demise of numerous neurons, and there is still no efficacious pharmacological intervention for it. Recently, studies have shown that endoplasmic reticulum stress (ERS) plays a pivotal role in recovery of neurological function after spinal cord injury. As a process to cope with intracellular accumulation of misfolded and unfolded proteins which triggers ERS, the unfolded protein response (UPR) plays an important role in maintaining protein homeostasis.

Novel dithiocarbamate derivatives are effective copper-dependent antimicrobials against species.

Despite the availability of several vaccines against multiple disease-causing strains of , the rise of antimicrobial resistance and pneumococcal disease caused by strains not covered by the vaccine creates a need for developing novel antimicrobial strategies. (DMDC) was found to be a potent copper-dependent antimicrobial against several pathogens, including . Here, DMDCs efficacy against pathogens , , and was tested using bactericidal and inductively coupled plasma - optical emission spectrometry.

Exploring the potential of RhoA inhibitors to improve exercise-recoverable spinal cord injury: A systematic review and meta-analysis.

Background: The spinal cord is one of the central nervous system. Spinal cord injury (SCI) will cause loss of physical function and dysfunction below the injury site, causing them to lose sensation and mobility, thereby reducing the quality of life of patients. Although regular rehabilitation management can reduce its severity, the current effective treatment methods are limited to the treatment of secondary injuries to SCI.

Design, synthesis and biological evaluation of tyrosine derivatives as Mcl-1 inhibitors.

The upregulation of the protein myeloid cell leukemia-1 (Mcl-1) is closely associated with various human cancers, which can result in the evasion of apoptosis and a low survival rate. Therefore, developing Mcl-1 inhibitors has become a promising paradigm for cancer therapy. Herein, we designed and synthesized a novel series of tyrosine derivatives, among which compounds 5g, 6l and 6c exhibited very high binding affinity to Mcl-1 with K values of 0.

Discovery and development of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives as Bcl-2/Mcl-1 inhibitors.

Bcl-2 family proteins play a vital role for cancer cell in escaping apoptosis, and small-molecule anti-apoptotic Bcl-2 protein inhibitors have been developed as new anticancer therapies. In current study, a series of substituted 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives were developed based on the lead compound 1 (K = 5.2 µM against Bcl-2 protein).

Discovery and development of substituted tyrosine derivatives as Bcl-2/Mcl-1 inhibitors.

Anti-apoptotic Bcl-2 family proteins are vital for cancer cells to escape apoptosis, which make them attractive targets for cancer therapy. Recently, a lead compound 1 was found to modestly inhibit the binding of BH3 peptide to Bcl-2 protein with a K value of 5.2 µM.

Design, synthesis and preliminary biological evaluation of indole-3-carboxylic acid-based skeleton of Bcl-2/Mcl-1 dual inhibitors.

The B-cell lymphoma-2 (Bcl-2) family proteins are attractive targets for cancer therapy. In our previous work, the structure-activity relationship of WL-276 was studied. According to the results, rhodanine derivatives show potent binding affinity for Bcl-2 and Mcl-1 protein and show weaker activity against Bcl-X protein.

Design and synthesis of a new generation of substituted purine hydroxamate analogs as histone deacetylase inhibitors.

Histone deacetylase inhibitors have been proved to be great potential for the treatment of cancer. Recently, we designed and modified a series of substituted purine hydroxamate analogs as potent HDAC inhibitors based on our previous studies. The target compounds were investigated for their in vitro HDAC inhibitory activities and anti-proliferative activities.

[Histone deacetylase 6: structure, functions and development of selective inhibitors].

Histone deacetylase 6 (HDAC6) is an unique subtype of histone deacetylases with two tandem deacetylase domains and substrate specificity for non-histone proteins. It is involved in many important physiological and pathological processes and has become a promising therapeutic target in recent decades. Different kinds of potent HDAC6-selective inhibitors have been reported around the world.

Enhancing the Sensitivity of Pharmacophore-Based Virtual Screening by Incorporating Customized ZBG Features: A Case Study Using Histone Deacetylase 8.

As key regulators of epigenetic regulation, human histone deacetylases (HDACs) have been identified as drug targets for the treatment of several cancers. The proper recognition of zinc-binding groups (ZBGs) will help improve the accuracy of virtual screening for novel HDAC inhibitors. Here, we developed a high-specificity ZBG-based pharmacophore model for HDAC8 inhibitors by incorporating customized ZBG features.