Structure-Guided Design of the First Noncovalent Small-Molecule Inhibitor of CRM1.

Nuclear export factor chromosome region maintenance 1 (CRM1) is an attractive anticancer and antiviral drug target that spurred several research efforts to develop its inhibitor. Noncovalent CRM1 inhibitors are desirable, but none is reported to date. Here, we present the crystal structure of yeast CRM1 in complex with S109, a substructure of CBS9106 (under clinical test).

Acinar cell NLRP3 inflammasome and gasdermin D (GSDMD) activation mediates pyroptosis and systemic inflammation in acute pancreatitis.

Background And Purpose: Pyroptosis is a lytic form of pro-inflammatory cell death characterised as caspase 1 dependent with canonical NLRP3 inflammasome-induced gasdermin D (GSDMD) activation. We aimed to investigate the role of acinar pyroptotic cell death in pancreatic injury and systemic inflammation in AP.

Experimental Approach: Pancreatic acinar pyroptotic cell death pathway activation upon pancreatic toxin stimulation in vitro and in vivo was investigated.

Aqueous extraction from dachengqi formula granules reduces the severity of mouse acute pancreatitis via inhibition of pancreatic pro-inflammatory signalling pathways.

Ethnopharmacological Relevance: Dachengqi decoction (DCQD) belongs to a family of purgative herbal formulas widely used in China for the treatment of acute pancreatitis (AP). AP is a prevalent digestive disease currently without an effective pharmacological intervention. Formula granules have become the preferred method for delivery of herbal formulation in China given its benefit of potency retention, dosing precision and ease of use.