A5021818883- Chronic Lymphocytic Leukemia Research
- Protein Degradation and Inhibitors
- Biochemical and Molecular Research
- Cancer, Hypoxia, and Metabolism
- Nanoplatforms for cancer theranostics
- 3D Printing in Biomedical Research
- Calcium signaling and nucleotide metabolism
- Molecular Communication and Nanonetworks
- Photodynamic Therapy Research Studies
- Nanotechnology research and applications
- Adenosine and Purinergic Signaling
- Toxin Mechanisms and Immunotoxins
- Lymphoma Diagnosis and Treatment
- Cerebrovascular and Carotid Artery Diseases
Nurix (United States)
2023-2024
Duke University
2014-2016
Increasing use of covalent and noncovalent inhibitors Bruton's tyrosine kinase (BTK) has elucidated a series acquired drug-resistant BTK mutations in patients with B cell malignancies. Here we identify inhibitor resistance distinct enzymatic activities, including some that impair activity while imparting novel protein-protein interactions sustain receptor (BCR) signaling. Furthermore, describe clinical-stage IKZF1/3 degrader, NX-2127, can bind proteasomally degrade each mutant proteoform,...
Abstract Chronic activation of Bruton’s Tyrosine Kinase (BTK) signaling is a hallmark B cell malignancies. Over the last decade, covalent and reversible inhibitors BTK have proven effective for treatment many these including chronic lymphocytic leukemia, diffuse large lymphoma, mantle marginal zone lymphoma Waldenstrom macroglobulinemia. However, long-term efficacy has been limited by both tolerability emergence acquired resistance mutations. Mutations at C481, example, dramatically reduce...
Abstract Small molecule kinase inhibitors have revolutionized the treatment of hematological malignancies by suppressing signaling pathways essential for tumor cell survival. Bruton’s Tyrosine Kinase (BTK) are widely used in clinic patients with B malignancies. Acquired resistance mutations, however, can reduce or eliminate their efficacy and represent a growing challenge. Mutations at C481 dramatically binding covalent BTK inhibitors, whereas other clinically-observed mutations such as...
Abstract Intratumoral (i.t.) drug delivery can circumvent the transport barriers_high intratumoral fluid pressure and irregular vascularization_of solid tumors that limit effectiveness of systemically delivered therapeutics. Unfortunately, long tumor retention coverage are difficult to concurrently optimize in most i.t. methodologies. One method overcome this limitation is design an system where initial dissemination system_as a liquid_can be independently controlled from its liquid-solid...
Several monoclonal antibodies and inhibitors targeting CD38, an ectoenzyme overexpressed on malignant plasma cells, have previously been discovered. Herein, we expand structure-activity relationships of reported small-molecule thiazoloquinolinones show that several 4-cyclohexylamino analogues potent binding affinity for CD38 using surface plasmon resonance. Moreover, active amine could be acylated functionalized with alkyne fluorescein groups. Fluorescein analogue 21 bound selectively to...