Structure-guided inhibitor design targeting CntL provides the first chemical validation of the staphylopine metallophore system in bacterial metal acquisition.

To survive in the metal-scarce environment within the host, pathogens synthesize various small molecular metallophores to facilitate the acquisition of transition metals. The cobalt and nickel transporter (Cnt) system synthesizes and transports staphylopine, a nicotianamine-like metallophore, and serves as a primary transition metal uptake system in Gram-positive bacteria including the human pathogen Staphylococcus aureus. In this study, we report the design of the first inhibitor of the Cnt system by targeting the key aminobutanoyltransferase CntL which is involved in the biosynthesis of staphylopine.

Biochemical and structural characterization of chlorhexidine as an ATP-assisted inhibitor against type 1 methionyl-tRNA synthetase from Gram-positive bacteria.

Methionyl-tRNA synthetase (MetRS) catalyzes the attachment of l-methionine (l-Met) to tRNA to generate methionyl-tRNA, an essential substrate for protein translation within ribosome. Owing to its indispensable biological function and the structural discrepancies with human counterpart, bacterial MetRS is considered an ideal target for developing antibacterials. Herein, chlorhexidine (CHX) was identified as a potent binder of Staphylococcus aureus MetRS (SaMetRS) through an ATP-aided affinity screening.

Discovery of the 2,4-disubstituted quinazoline derivative as a novel neddylation inhibitor for tumor therapy.

Overactivation of neddylation has been found in a number of common human tumor-related diseases. In recent years, targeting the neddylation pathway has become an appealing anti-cancer strategy, and it is critical to find neddylation inhibitors with novel structures and higher efficacy. Here, we present the discovery of novel inhibitors of the NEDD8-activating enzyme (NAE) and their antitumor activity in vitro.

Design, synthesis and biological evaluation of novel tubulin inhibitors targeting colchicine sites.

Tubulin, a potential target for antitumor drug discovery, contains three main binding sites for clinical inhibitors: colchicine, vinblastine, and paclitaxel. CA-4 has been reported to be a classic tubulin inhibitor targeting the colchicine site. Herein, based on the structural modification of CA-4, 48 novel compounds were designed and synthesized by selecting structural fragments with various biological activities to replace the cis double bond of CA-4.

APJ/apelin: A promising target for the treatment of retinopathy of prematurity.

Retinopathy of prematurity is a noticeable retinal abnormality causing common blindness in children. An uncontrolled retinal vasculature in retinopathy of prematurity inflicts vision loss in numerous children despite the accessibility to a wide range of clinical treatments prescribed for retinopathy of prematurity. Apelin/APJ [class A (rhodopsin-like) G-protein-coupled receptor] signaling regulates retinopathy of prematurity augmented with uncontrolled angiogenesis.

The role of MOZ/KAT6A in hematological malignancies and advances in MOZ/KAT6A inhibitors.

Hematological malignancies, unlike solid tumors, are a group of malignancies caused by abnormal differentiation of hematopoietic stem cells. Monocytic leukemia zinc finger protein (MOZ), a member of the MYST (MOZ, Ybf2/Sas3, Sas2, Tip60) family, is a histone acetyltransferase. MOZ is involved in various cellular functions: generation and maintenance of hematopoietic stem cells, development of erythroid cells, B-lineage progenitors and myeloid cells, and regulation of cellular senescence.

NQO1-Selective Activated Prodrug of Triptolide: Synthesis and Antihepatocellular Carcinoma Activity Evaluation.

Hepatocellular carcinoma (HCC) is the leading cause of death in patients with cirrhosis. Due to its poor response to conventional chemotherapy drugs, the prognosis for its survival is the worst. NAD(P)H:quinone oxidoreductase 1 (NQO1) is an attractive anticancer target due to its overexpression in HCC.