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 >

Unlike conventional protein-targeted therapies, nucleic acid therapeutics have the potential for long-lasting effects and greater target specificity. WuXi AppTec provides a comprehensive platform to support the discovery of mRNA drugs.  Our services include mRNA design and production, assessment of mRNA delivery systems, in vitro evaluation, and determination of in vivo efficacy and biodistribution. At AACR …Read More >

An inevitable challenge emerges over time as tumors develop drug resistance, resulting in treatment failure.  The development of targeted therapies for overcoming drug resistance represents an unmet medical need. Patient-derived xenografts (PDXs) represent a powerful platform for cancer drug screening and biomarker discovery and are considered the gold standard of in vivo models for their …Read More >