Welcome to your August Newsletter!
WuXi Discovery Services
Driving drug discovery through world-class capabilities, dedicated collaborative teams, and scientific excellence.
View the Video | Paclitaxel-Induced Resistant Tumor Models
Despite excellent clinical responses to paclitaxel therapy, drug resistance inevitably develops. The discovery of targeted therapies for overcoming drug resistance represents an unmet medical need. WuXi Biology has established gastric cancer and breast cancer cell lines that are stably resistant to paclitaxel. We have also established corresponding in vivo tumor models for these cell lines which exhibit significant resistance.
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On-Demand Webinar | Research Strategies for Protein Degraders
In our latest webinar, experts present research strategies and integrated solutions for the discovery of targeted protein degraders (TPD). Since 2016, WuXi AppTec has built a comprehensive TPD discovery service platform, adept in over 20 assay formats to investigate the full TPD functional cycle from binary/ternary complex formation and protein ubiquitination to degradation.
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Publication | PD/PK Profile of a Novel GLP-1 Receptor Biased Agonist
To improve the design of GLP-1 receptor-biased agonists with enhanced druggability, a novel small molecule, designated SAL0112, was developed. WuXi AppTec contributed to a study which characterized the PD/PK profile of SAL0112. The findings in this work suggest that SAL0112 has the potential to offer an improved pharmacokinetic profile in the clinic.
Access full article: USP7 Inhibitors Reveal a Differentiated Mechanism of p53-Driven Anti-Cancer Activity
Publication | Differentiated Mechanism of p53 Anticancer Activity
USP7 deubiquitinates and stabilizes MDM2, which promotes degradation of p53. WuXi AppTec contributed to a study illustrating the mechanistic differences between USP7 and MDM2 inhibitors and their effects on p53 signaling. This work highlights the therapeutic potential of USP7 inhibitors for their use in the treatment of AML.
Access full article: USP7 Inhibitors Reveal a Differentiated Mechanism of p53-Driven Anti-Cancer Activity
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Publication | Preclinical Evaluation of a SARS-CoV-2 Mpro Inhibitor
WuXi AppTec contributed to a research article 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
Access full article: Preclinical Evaluation of the SARS-CoV-2 Mpro Inhibitor RAY1216
Publication | DEL Hit: A µ-Opioid Receptor Modulator
Stanford researchers identified a selective negative allosteric modulator for the μ-opioid receptor using DNA-encoded library technology. The compound was discovered directly from WuXi AppTec’s DEL product and exhibited in vivo efficacy without any modifications, showing an effective application of DEL in identifying novel hits for GPCR targets.
View the abstract: A µ-Opioid Receptor Modulator that Works Cooperatively with Naloxone
Publication | Cardiac Manifestations of Fabry Disease
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 and cardiovascular dysfunctions. Current treatments can preserve kidney function but are not very effective in preventing progression of cardiovascular pathology, which remains the most common cause of premature death in FD patients. There is a significant need for a translational model that could be used for testing the cardiac efficacy of new drugs to treat FD. WuXi AppTec contributed to a study which revealed that Gla KO mice exhibit several cardiac dysfunctions characteristic of the initial stages of Fabry cardiac pathology.
Access full article: Cardiac Manifestations of Fabry Disease
Poster | mRNA-Encoded Modulators Suppress Tumor Growth
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 2024, WuXi AppTec presented a poster showcasing the anti-tumor properties of mRNA-encoded CD3-EpCAM bispecific antibody (BsAb) and mRNA-encoded IL-12 protein. The results showed that these two mRNAs exhibited anti-tumor activity and activated immune cells both in vitro and in vivo.
Download poster: mRNA-Encoded Modulators Suppress Tumor Growth