A5050224498- Chronic Lymphocytic Leukemia Research
- Radiopharmaceutical Chemistry and Applications
- Cell death mechanisms and regulation
- Cancer-related Molecular Pathways
- Medical Imaging Techniques and Applications
- X-ray Diffraction in Crystallography
- PI3K/AKT/mTOR signaling in cancer
- Crystallization and Solubility Studies
- Lymphoma Diagnosis and Treatment
- Neurotransmitter Receptor Influence on Behavior
- Phenothiazines and Benzothiazines Synthesis and Activities
- Monoclonal and Polyclonal Antibodies Research
- Neuroscience and Neuropharmacology Research
- Piezoelectric Actuators and Control
- Chemical Synthesis and Analysis
- Medical Imaging and Pathology Studies
- Synthesis and Biological Evaluation
- Radioactive element chemistry and processing
- Forensic Toxicology and Drug Analysis
- Structural and Chemical Analysis of Organic and Inorganic Compounds
- Orthopaedic implants and arthroplasty
- CAR-T cell therapy research
- Topology Optimization in Engineering
BeiGene (China)
2015-2024
Beijing Normal University
2006-2008
Ministry of Education of the People's Republic of China
2008
Aberrant activation of Bruton's tyrosine kinase (BTK) plays an important role in pathogenesis B-cell lymphomas, suggesting that inhibition BTK is useful the treatment hematological malignancies. The discovery a more selective on-target covalent inhibitor high value. Herein, we disclose and preclinical characterization potent, selective, irreversible as our clinical candidate by using vitro potency, selectivity, pharmacokinetics (PK), vivo pharmacodynamic for prioritizing compounds. Compound...
Abstract Venetoclax, the first-generation inhibitor of apoptosis regulator B-cell lymphoma 2 (BCL2), disrupts interaction between BCL2 and proapoptotic proteins, promoting in malignant cells. Venetoclax is mainstay therapy for relapsed chronic lymphocytic leukemia under investigation multiple clinical trials treatment various cancers. Although venetoclax can result high rates durable remission, relapse has been widely observed, indicating emergence drug resistance. The G101V mutation...
The approval of venetoclax, a B-cell lymphoma-2 (Bcl-2) selective inhibitor, for the treatment chronic lymphocytic leukemia demonstrated that antiapoptotic protein Bcl-2 is druggable target malignancies. However, venetoclax's limited potency cannot produce strong, durable clinical benefit in other Bcl-2-mediated malignancies (e.g., diffuse large lymphomas) and multiple recurrent mutations G101V) have been reported to mediate resistance venetoclax after long-term treatment. Herein, we...
Abstract BTK, an essential component of the BCR pathway, has emerged as novel target in treatment B-cell malignancies. Although Ibrutinib, first-in-class irreversible inhibitor showed promising clinical activity, recent study revealed that ibrutinib could antagonize rituximab induced antigen-dependent cell-mediated cytotoxicity (ADCC) by inhibiting ITK kinase activity (Kohrt et. al., 2013), suggesting potential limitations its application. BGB-3111 is a novel, highly selective, second...
Abstract The ability to evade apoptosis is a hallmark of cancer. B-cell lymphoma-2 (Bcl-2), an anti-apoptosis protein, overexpressed and leads oncogenesis or drug resistance in various tumor types, including lymphoma leukemia. Bcl-2 well-validated target for B cell malignancies as demonstrated by inhibitor venetoclax which was recently approved the treatment chronic lymphocytic leukemia (CLL) currently phase III clinical development other hematologic malignancies. With longer term treatment,...
Bruton's tyrosine kinase (BTK) plays an essential role in B-cell receptor (BCR)-mediated signaling as well the downstream pathway for Fc receptors (FcRs). Targeting BTK malignancies by interfering with BCR has been clinically validated some covalent inhibitors, but suboptimal selectivity may lead to adverse effects, which also makes clinical development of autoimmune disease therapy more challenging. The structure-activity relationship (SAR) starting from zanubrutinib (BGB-3111) leads a...
In the title compound, two aromatic rings are almost perpendicular to each other with a dihedral angle of 72.4 (1)°.
Developing appropriate analytic-function-based constitutive models for new materials with nonlinear mechanical behavior is demanding. For such kinds of materials, it more challenging to realize the integrated design from collection material experiment under classical topology optimization framework based on models. The present work proposes a mechanistic-based data-driven (DDTO) three-dimensional continuum structures finite deformation. In DDTO framework, help neural networks and explicit...