The recent publication in the journal Organic Letters, ‘DNA-Compatible Cyclization Reaction to Access 1,3,4-Oxadiazoles & 1,2,4-Triazoles‘ by our WuXi Biology DEL team, introduces two novel DNA-compatible reactions, successfully incorporating bioactive cores 1,3,4-oxadiazoles and 1,2,4-triazoles into the DEL library. These cores are reported to show broad ranges of biological activities, such as antiviral, anti-inflammatory, anticancer, antifungal, …Read More >

The contribution of the X-ray crystallography team from our WuXi AppTec site in Germany was acknowledged in a recent study published in the journal Cancer Discovery. In this study, the authors show that compound STX-478, an allosteric PI3Kα inhibitor, selectively targets prevalent PI3Kα helical- and kinase-domain mutant tumors. STX-478 demonstrated robust efficacy in human tumor …Read More >

A growing body of in vitro and in vivo evidence has demonstrated that trace amine-associated receptor 1 (TAAR1) could negatively modulate monoamine transmission and play a crucial role in many psychiatric disorders, including schizophrenia, depression, and anxiety. WuXi AppTec contributed to a review article in the journal Pharmacology & Therapeutics, discussing the current understanding of …Read More >

DNA-encoded libraries from WuXi AppTec were used in a “steered” screening against either inactive or active μ-opioid receptors in parallel, to find novel negative allosteric modulators of this receptor. The molecule discovered via DEL screening not only shows direct and effective in vitro and in vivo potency, but also helps elucidate the mechanism of negative allosteric modulation of GPCRs. This discovery …Read More >

DNA-dependent protein kinase (DNA-PK) plays an important role in the overall survival and proliferation of cells, making this enzyme an intriguing target for the treatment of a variety of cancers.  In our latest publication, WuXi AppTec scientists contributed to the discovery and characterization of ZL-2201, a potent and highly selective small molecule DNA-PK inhibitor.  In …Read More >

On-target, off-tumor toxicity is a specific type of toxic side effect that limits the anticancer applicability of chimeric antigen receptor (CAR) T cells. In our latest publication, WuXi AppTec scientists contributed to a study describing how the tumor-targeting specificity and activity of T cells with a CAR (consisting of an antibody that catalytically forms a …Read More >

The KRAS G12D mutation subtype is present in over 40% of pancreatic ductal adenocarcinomas (PDAC), making this an important drug target.  WuXi AppTec scientists recently contributed to a research article in ACS Med. Chem. Letters describing the optimization of a series of potent and selective KRAS G12D inhibitors through a structure-based drug design approach.  The …Read More >

The metabotropic glutamate receptor mGluR7 is widely expressed throughout the CNS and has been implicated in numerous CNS disorders.  WuXi AppTec scientists recently contributed to a study which led to the identification, optimization, and characterization of a highly potent, novel mGluR7 allosteric agonist, designated CVN636.  The authors show that CVN636 has high selectivity toward mGluR7, …Read More >

WuXi AppTec scientists recently contributed to a study which led to the discovery and optimization of a novel series of GST inhibitors. The authors used affinity mediated DEL selection against a privileged scaffold to identify a compound with potent inhibition against SjGST and GSTM2. SAR studies, coupled with X-ray crystallography and structural analysis, revealed that …Read More >