Knowledge Library
Control of the Antitumor Activity and Specificity of CAR T Cells via Organic Adapters Covalently Tethering the CAR to Tumor Cells
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 >
Structure-Based Design and Synthesis of Potent and Selective KRAS G12D Inhibitors
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 >
Discovery of CVN636: A Highly Potent, Selective, and CNS Penetrant mGluR7 Allosteric Agonist
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 >
Discovery of Novel GST Inhibitors Identified from a DNA-Encoded Library
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 >
Discovery and Characterization of Proteolysis Targeting Chimeras: Tissue Transglutaminase
Tissue transglutaminase (TG2) is a multifunctional enzyme activated in several pathological conditions, including cancer. WuXi AppTec recently contributed to a study which used a targeted protein degradation strategy to abolish TG2’s myriad of functions. The authors synthesized and characterized a series of VHL-based degraders that reduce TG2 in ovarian cancer cells in a proteasome-dependent manner.
Discovery and preclinical profile of LX-039, a novel indole-based oral selective estrogen receptor degrader (SERD)
WuXi AppTec scientists contributed to a study which identified a novel, indole-based, selective estrogen receptor degrader (SERD), designated LX-039. The authors show that LX-039 exhibits potent activity in ER degradation and proliferation assays. With favorable ADME/PK properties, LX-039 also exhibits higher efficacy in a tamoxifen-resistant MCF7 CDX model compared to fulvestrant, with up to 90% inhibition …Read More >
DELs enable the development of BRET probes for target engagement studies in cells
WuXi AppTec scientists recently contributed to a research article in Cell Chemical Biology demonstrating the successful conversion of ligands identified from DNA-encoded library (DEL) screening into highly functional, cell-active, bioluminescence resonance energy transfer (BRET) probes. The authors show that analyzing preliminary DEL hits based on target occupancy data generated in live, intact cells is an …Read More >
Inhibition of the hERG potassium ion channel by non-nucleoside CMV polymerase antiviral inhibitors
WuXi AppTec scientists collaborated on a study to characterize a series of pyrroloquinoline derivatives that were designed and synthesized to understand the effect of various substitutions on human cytomegalovirus (HCMV) polymerase activity, antiviral activity, and hERG inhibition. Results suggest that substitutions can be fine-tuned to reduce hERG inhibition while maintaining HCMV antiviral potency. The abstract …Read More >
TEAD Proteins Associate With DNA Repair Proteins to Facilitate Cellular Recovery
WuXi AppTec scientists recently contributed to a research study which utilized an affinity purification mass spectrometry approach to identify nuclear interacting partners of Transcriptional Enhanced Associate Domain (TEAD) proteins. The authors found a significant enrichment of interacting proteins linked to DNA damage, and they showed that depletion of TEAD transcription factors makes cells more susceptible …Read More >