SARS-CoV-2 antivirals which have been clinically approved or are in late-stage development are directed against either the RNA-dependent RNA polymerase (RdRp) or the main protease (Mpro). With the possibility of resistance developing over time, there is a need for additional oral antivirals directed against currently undrugged viral targets. Conserved across coronaviruses, the SARS-CoV-2 papain-like protease …Read More >

Casitas B lymphoma-b (Cbl-b), a RING finger E3 ubiquitin ligase, is a key regulator of T cell activation and plays an important role in immune responses against tumors.  Cbl-b has been identified as an attractive target for cancer immunotherapy due to its role in promoting an immunosuppressive tumor environment. WuXi AppTec contributed to a study …Read More >

Lysosomal storage disorders are rare genetic conditions that cause a buildup of toxic materials in the cells of various organs. Fabry disease (FD) is an X-linked disorder of glycosphingolipid metabolism caused by mutations in the GLA gene encoding alpha-galactosidase A. Manifestations of FD include life-threatening renal, cardiovascular, and cerebrovascular dysfunctions. Current treatments can preserve kidney …Read More >

Glucagon‐like peptide‐1 (GLP-1) receptor agonists have emerged as promising therapeutic options for addressing type‐2 diabetes, obesity, and related conditions. However, because of the continued need for injectable administration, many GLP-1 agonists face compliance challenges. To improve the design and production of GLP-1 receptor biased agonists with enhanced druggability, a novel small molecule, designated SAL0112, was …Read More >

Ubiquitin-specific protease 7 (USP7) is a deubiquitinating enzyme that cleaves ubiquitin from a range of substrates, shielding them from degradation by the proteasome. USP7 activity has been implicated in cancer progression and its overexpression is associated with tumor aggressiveness and poor prognosis in a variety of cancer types, making USP7 inhibition an attractive strategy for …Read More >

WuXi AppTec scientists contributed to a research article in the journal Nature Microbiology, which characterized a peptidomimetic inhibitor of the SARS-CoV-2 main protease (Mpro).  In a human ACE2 transgenic mouse model, this inhibitor (designated RAY1216) exhibited antiviral activities against SARS-CoV-2 comparable to those of nirmatrelvir, but with improved pharmacokinetics.

G-protein coupled receptors (GPCRs) play a pivotal role in signaling pathways, and these transmembrane proteins represent an important drug target class. The majority of approved drugs that target GPCRs bind to traditional orthosteric sites. In a recent publication in Nature, Professor Brian Kobilka and his team at Stanford University successfully identified selective negative allosteric modulators …Read More >

WuXi AppTec scientists published a study in the open access archive ChemRxiv describing the discovery of highly selective, novel, heme oxygenase-1 (HO-1) targeting molecules. HO-1, primarily a heme-degrading enzyme, has been identified as a potential therapeutic target in diseases such as cancer and neurodegenerative disorders. Here, we report the discovery of five series of novel …Read More >

WuXi AppTec scientists contributed to a research article in the journal Translational Medicine Communications which characterized the antitumor immune responses generated by iMN041, a prodrug of a DNA methyl transferase/ribonucleotide reductase inhibitor.  This study also assessed the efficacy of iMN041 in mouse xenografts of human clear cell renal cell cancer, pancreatic cancer, and triple negative …Read More >