Subtle Structural Modifications Spanning from EP4 Antagonism to EP2/EP4 Dual Antagonism: A Novel Class of Thienocyclic-Based Derivatives.

The development of dual prostaglandin E receptors 2/4 (EP2/EP4) antagonists represents an attractive strategy for cancer immunotherapy. Herein, a series of 4,7-dihydro-5-thieno[2,3-]pyran derivatives with potent EP2/EP4 dual antagonism were discovered by fine-tuned structural modifications. The biphenyl side chain was found to be the key pharmacophore for the transition from EP4 antagonism to EP2/EP4 dual antagonism.

Discovery of a Highly Potent Oxysterol Receptor GPR183 Antagonist Bearing the Benzo[]thiazole Structural Motif for the Treatment of Inflammatory Bowel Disease (IBD).

Accumulating evidence has demonstrated a critical pathological role of oxysterol receptor GPR183 in various inflammatory and autoimmune diseases, including inflammatory bowel disease (IBD). However, the currently reported GPR183 antagonists are very limited and not qualified for studies due to their inferior druglike properties. Herein, we conducted a structural elaboration focusing on improving its PK and safety profile based on a reference antagonist NIBR189.

Discovery of Pyridinone Derivatives as Potent, Selective, and Orally Bioavailable Adenosine A Receptor Antagonists for Cancer Immunotherapy.

Recent studies and clinical evidence have strongly supported the development of adenosine A receptor (AR) antagonists as novel approaches for cancer immunotherapy. By screening our in-house compound library, a pyridinone hit compound () with weak AR antagonistic activity was identified. Further structure-activity relationship studies revealed a series of pyridinone derivatives with strong potency.

A Novel Small Molecular Prostaglandin Receptor EP4 Antagonist, L001, Suppresses Pancreatic Cancer Metastasis.

Metastatic pancreatic cancer remains a major clinical challenge, emphasizing the urgent need for the exploitation of novel therapeutic approaches with superior response. In this study, we demonstrate that the aberrant activation of prostaglandin E (PGE) receptor 4 (EP4) is a pro-metastatic signal in pancreatic cancer. To explore the therapeutic role of EP4 signaling, we developed a potent and selective EP4 antagonist L001 with single-nanomolar activity using a panel of cell functional assays.

Hemophagocytic lymphohistiocytosis secondary to and reactivated EBV infections: A case report and review of the literature.

Hemophagocytic lymphohistiocytosis (HLH) has been recognized as a potentially life-threatening syndrome. This is the first case of acquired HLH caused by dual infections with Candida albicans and reactivated EBV infections, which focuses on the importance of morphological awareness of peripheral blood and bone marrow because sometimes they are the only locations that HLH and fungal microorganisms can be diagnosed. A 29-year-old woman with a history of abdominal distension and 9 months of intermittent fevers ($38.

From a Designer Drug to the Discovery of Selective Cannabinoid Type 2 Receptor Agonists with Favorable Pharmacokinetic Profiles for the Treatment of Systemic Sclerosis.

Synthetic cannabinoids, as exemplified by SDB-001 (), bind to both CB1 and CB2 receptors and exert cannabimimetic effects similar to (-)--Δ-tetrahydrocannabinol, the main psychoactive component present in the cannabis plant. As CB1 receptor ligands were found to have severe adverse psychiatric effects, increased attention was turned to exploiting the potential therapeutic value of the CB2 receptor. In our efforts to discover novel and selective CB2 receptor agonists, was selected as a starting point for hit molecule identification and a class of 1-pyrazole-3-carboxamide derivatives were thus designed, synthesized, and biologically evaluated.

Atypical Acute Monocytic Leukemia: a Lymphoma Presentation and Association with Complex Karyotype.

A 71-year-old woman presented with acute monocytic leukemia with lymphoma-like morphologic features and an unusual complex karyotype. Bone marrow (BM) aspiration revealed acute monocytic leukemia with lymphoma-like morphologic features. Thus, we called the condition a lymphoma presentation.

Reductive dechlorination and mineralization of pentachlorophenol in biocathode microbial fuel cells.

Simultaneous anaerobic and aerobic degradation pathways in two-chamber, tubular microbial fuel cells (MFCs) facilitated pentachlorophenol (PCP) mineralization by a mediator-less biocathode. PCP was degraded at a rate of 0.263 ± 0.

Effect of set potential on hexavalent chromium reduction and electricity generation from biocathode microbial fuel cells.

Setting a biocathode potential at -300 mV improved the subsequent performance of an MFC for Cr(VI) reduction compared to a control (no set potential). With this set potential, the startup time was reduced to 19 days, the reduction of Cr(VI) was improved to 19.7 mg/L d, and the maximum power density was increased to 6.