Identifying selective agonists targeting LXRβ from terpene compounds of alismatis rhizoma.

Hyperlipidemia is thought of as an important contributor to coronary disease, diabetes, and fatty liver. Liver X receptor β (LXRβ) was considered as a validated target for hyperlipidemia therapy due to its role in regulating cholesterol homeostasis and immunity. However, many current drugs applied in clinics are not selectively targeting LXRβ, and they can also activate LXRα which activates SREBP-1c that worked as an activator of lipogenic genes.

Screening of novel histone deacetylase 7 inhibitors through molecular docking followed by a combination of molecular dynamics simulations and ligand-based approach.

Histone acetylation/deacetylation is a key mechanism for transcription regulation which plays an important role in control of gene expression, tissue growth, and development. In particular, histone deacetylase 7 (HDAC7), a member of class IIa HDACs, is crucial to maintain cell homeostasis, and HDAC7 has emerged as a new target for cancer therapy. In this study, molecular docking was applied to screen candidate inhibitors and 21 compounds were found.

Structure and energy based quantitative missense variant effect analysis provides insights into drug resistance mechanisms of anaplastic lymphoma kinase mutations.

Anaplastic lymphoma kinase (ALK) is considered as a validated molecular target in multiple malignancies, such as non-small cell lung cancer (NSCLC). However, the effectiveness of molecularly targeted therapies using ALK inhibitors is almost universally limited by drug resistance. Drug resistance to molecularly targeted therapies has now become a major obstacle to effective cancer treatment and personalized medicine.

Structure and function analysis of Polygonatum cyrtonema lectin by site-directed mutagenesis.

The crystal structure of mature Polygonatum cyrtonema lectin (PCL) showed three similar carbohydrate-binding sites (CBS I, CBS II, and CBS III). The Gln58 and Asp60 residues of CBS II are substituted with His58 and Asn60. To establish the relationship between the key amino acid residues and structure or activity of PCL, we constructed four recombinant mutants in CBS I, CBS II, and CBS III.

In silico identification of potential inhibitors targeting Streptococcus mutans sortase A.

Dental caries is one of the most common chronic diseases and is caused by acid fermentation of bacteria adhered to the teeth. Streptococcus mutans (S. mutans) utilizes sortase A (SrtA) to anchor surface proteins to the cell wall and forms a biofilm to facilitate its adhesion to the tooth surface.

Insight into drug resistance mechanisms and discovery of potential inhibitors against wild-type and L1196M mutant ALK from FDA-approved drugs.

Anaplastic lymphoma kinase (ALK) plays a crucial role in multiple malignant cancers. It is known as a well-established target for the treatment of ALK-dependent cancers. Even though substantial efforts have been made to develop ALK inhibitors, only crizotinib, ceritinib, and alectinib had been approved by the U.

Discovery of a Potential HER2 Inhibitor from Natural Products for the Treatment of HER2-Positive Breast Cancer.

Breast cancer is one of the most lethal types of cancer in women worldwide due to the late stage detection and resistance to traditional chemotherapy. The human epidermal growth factor receptor 2 (HER2) is considered as a validated target in breast cancer therapy. Even though a substantial effort has been made to develop HER2 inhibitors, only lapatinib has been approved by the U.

An Overview of Predictors for Intrinsically Disordered Proteins over 2010-2014.

The sequence-structure-function paradigm of proteins has been changed by the occurrence of intrinsically disordered proteins (IDPs). Benefiting from the structural disorder, IDPs are of particular importance in biological processes like regulation and signaling. IDPs are associated with human diseases, including cancer, cardiovascular disease, neurodegenerative diseases, amyloidoses, and several other maladies.

Discover natural compounds as potential phosphodiesterase-4B inhibitors via computational approaches.

cAMP, intracellular cyclic adenosine monophosphate, is a ubiquitous second messenger that plays a key role in many physiological processes. PDE4B which can reduce the cAMP level by hydrolyzing cAMP to 5'-AMP has become a therapeutic target for the treatment of human diseases such as respiratory disorders, inflammation diseases, neurological and psychiatric disorders. However, the use of currently available PDE4B inhibitors is restricted due to serious side effects caused by targeting PDE4D.