A5017581192- Computational Drug Discovery Methods
- Protein purification and stability
- Monoclonal and Polyclonal Antibodies Research
- Cytokine Signaling Pathways and Interactions
- Biosimilars and Bioanalytical Methods
- PI3K/AKT/mTOR signaling in cancer
- Viral Infectious Diseases and Gene Expression in Insects
- Chronic Lymphocytic Leukemia Research
- Pharmaceutical Economics and Policy
- Innovative Microfluidic and Catalytic Techniques Innovation
- Click Chemistry and Applications
- Protein Degradation and Inhibitors
- Mast cells and histamine
- Analytical Chemistry and Chromatography
- Biochemical and Molecular Research
- Histone Deacetylase Inhibitors Research
- Eosinophilic Disorders and Syndromes
- Machine Learning in Bioinformatics
- Helicobacter pylori-related gastroenterology studies
- Breast Cancer Treatment Studies
- Engineering Technology and Methodologies
- Protein Structure and Dynamics
- Robotic Mechanisms and Dynamics
- Ferroelectric and Negative Capacitance Devices
- Asthma and respiratory diseases
Bristol-Myers Squibb (United States)
2024-2025
Jiangnan University
2021-2024
Bristol-Myers Squibb (Germany)
2023-2024
Amgen (United States)
2017-2024
Wuxi Fourth People's Hospital
2021
Chemical stability is a major concern in the development of protein therapeutics due to its impact on both efficacy and safety. Protein "hotspots" are amino acid residues that subject various chemical modifications, including deamidation, isomerization, glycosylation, oxidation etc. A more accurate prediction method for potential hotspot would allow their elimination or reduction as early possible drug discovery process. In this work, we focus models asparagine (Asn) deamidation....
Biologic drug discovery pipelines are designed to deliver protein therapeutics that have exquisite functional potency and selectivity while also manifesting biophysical characteristics suitable for manufacturing, storage, convenient administration patients. The ability use computational methods predict properties from sequence, potentially in combination with high throughput assays, could decrease timelines increase the success rates therapeutic developability engineering by eliminating...
Efficiency metrics are useful in medicinal chemistry to track small molecule progress lead optimization (LO). Molecular glue degraders molecules that mediate targeted protein degradation by chemically inducing proximity between an E3 ligase and a target. The potency depth of important factors identifying molecular drug candidates. We developed efficiency based on both objectives. applied these retrospectively clinical degrader series, resulting the identification Golcadomide (CC-99282). This...
Cereblon (CRBN) has been successfully co-opted to affect the targeted degradation of "undruggable" proteins with immunomodulatory imide drugs (IMiDs). IMiDs act as molecule glues that facilitate ternary complex formation between CRBN and a target protein, leading ubiquitination proteasomal degradation. Subtle structural modifications often cause profound sometimes unpredictable changes in selectivity. Herein, we utilize enantioselective cyclopropanation cyclopropenation on intact...
Abstract Extensive research has accumulated suggesting that Janus kinase 3 (JAK3) is closely related to the occurrence and development of various human diseases, making JAK3 a highly potential drug target. However, high homology with other members JAK family, inhibitors full challenges. Thus, here, naïve Bayesian classification (NBC) model based on multiple protein conformations, which integrates molecular docking, pharmacophore, descriptors, developed find novel inhibitors. First,...
Efficiency metrics are a simple and effective medicinal chemistry tool to track small molecule progress toward preferred profile in lead optimization. Targeted protein degradation can be mediated by molecules that act as molecular glue between an E3 ligase target. Molecular compounds characterized the potency depth of their dose response measurement, representing additional complexity identifying drug candidates. We developed efficiency based on both degradation. They serve basic scoring...
Efficiency metrics are a simple and effective medicinal chemistry tool to track small molecule progress toward preferred profile in lead optimization. Targeted protein degradation can be mediated by molecules that act as molecular glue between an E3 ligase target. Molecular compounds characterized the potency depth of their dose response measurement, representing additional complexity identifying drug candidates. We developed efficiency based on both degradation. They serve basic scoring...
The use of Monoclonal Antibodies (MAbs) as therapeutics has been increasing over the past 30 years due to their high specificity and strong affinity toward target. One major challenges drugs is low thermostability, which impacts both efficacy well manufacturing delivery.To aid design thermally more stable mutants, consensus sequence-based method widely used. These methods typically have a success rate about 50% with maximum melting temperature increment ranging from 10 32°C. To improve...
Abstract The use of Monoclonal Antibodies (MAbs) as therapeutics has been increasing over the past 30 years due to their high specificity and strong affinity towards target. One major challenges drugs is low thermostability, which impacts both efficacy well manufacturing delivery. To aid design thermally more stable mutants, consensus sequence-based method widely used. These methods typically have a success rate about 50% with maximum melting temperature increment ranging from 10 32°C. In...
Abstract Introduction Asthma is a chronic airway inflammatory disease of the airways characterized by involvement numerous cells and factors. Therefore, targeting inflammation one crucial strategies for developing novel drugs in treatment asthma. Phosphoinositide 3-kinase gamma (PI3Kγ) has been demonstrated to have significant impact on immune responses, thus emerging as promising therapeutic target disease, including Objective method There are few studies reporting effects PI3Kγ-selective...
ABSTRACT Computational chemistry and machine learning are used in drug discovery to predict target-specific pharmacokinetic properties of molecules. Multiparameter optimization (MPO) functions summarize multiple into a single score, aiding compound prioritization. However, over-reliance on subjective MPO risks reinforcing human bias. Mechanistic modeling approaches based physiological relevance can be adapted meet different potential key objectives the project (e.g. minimizing dose,...
Through machine learning, identifying correlations between amino acid sequences of antibodies and their observed characteristics, we developed an internal viscosity prediction model to empower the rapid engineering therapeutic antibody candidates. For a highly viscous anti-IL-13 monoclonal antibody, used structure-based rational design strategy generate list variants that were hypothesized mitigate viscosity. Our tool was then as screen cull virtually engineered with probability high while...
Computational chemistry and machine learning are used in drug discovery to predict the target-specific pharmacokinetic properties of molecules. Multiparameter optimization (MPO) functions summarize multiple into a single score, aiding compound prioritization. However, over-reliance on subjective MPO risks reinforcing human bias. Mechanistic modeling approaches based physiological relevance can be adapted meet different potential key objectives project (e.g., minimizing dose, maximizing...
Abstract Numerous research studies have demonstrated the significant correlation of phosphatidylinositol‐3 kinase gamma (PI3Kγ) with onset and progression various human diseases, highlighting PI3Kγ as a promising therapeutic target. However, demonstrates considerable similarity other isoforms in PI3K family, presenting challenges creation inhibitors. This study presents an ensemble‐based virtual screening approach to discover novel inhibitors targeting PI3Kγ. Eganelisib (IPI‐549) is sole...
Efficiency metrics are a simple and effective medicinal chemistry tool to track small molecule progress toward preferred profile in lead optimization. Targeted protein degradation can be mediated by molecules that act as molecular glue between an E3 ligase target. Molecular compounds characterized the potency depth of their dose response measurement, representing additional complexity identifying drug candidates. We developed efficiency based on both degradation. They serve basic scoring...
High breast density is significantly associated with an increased risk of diseases. Presently, suspected masses assessed as Breast Imaging-Reporting and Data System (BI-RADS) grade 4 provide a wide range positive predictive values. Moreover, subcategories (4a, 4b, 4c) are still under consideration the diagnostic criteria neither comprehensive nor objective. However, whether mammography (MBD) has any impact on accurate grading BI-RADS by ultrasound (US) remains unknown.A total 1,086 women...