A5035280620- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Peptidase Inhibition and Analysis
- Cytokine Signaling Pathways and Interactions
- Lysosomal Storage Disorders Research
- Crystallization and Solubility Studies
- Glycogen Storage Diseases and Myoclonus
- Cancer Mechanisms and Therapy
- X-ray Diffraction in Crystallography
- Neurological disorders and treatments
- Multiple Myeloma Research and Treatments
- Genetics and Neurodevelopmental Disorders
- Immunodeficiency and Autoimmune Disorders
- T-cell and B-cell Immunology
- Nonlinear Optical Materials Studies
- interferon and immune responses
- Lung Cancer Treatments and Mutations
- Click Chemistry and Applications
- Immune Cell Function and Interaction
- Ubiquitin and proteasome pathways
- Glioma Diagnosis and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Diamond and Carbon-based Materials Research
- Protein Tyrosine Phosphatases
- Force Microscopy Techniques and Applications
University of Toronto
2017-2025
Hospital for Sick Children
2012-2013
Hyper-activated STAT5B variants are high value oncology targets for pharmacologic intervention. STAT5BN642H, a frequently-occurring oncogenic driver mutation, promotes aggressive T-cell leukemia/lymphoma in patient carriers, although the molecular origins remain unclear. Herein, we emphasize nature of STAT5BN642H driving neoplasia upon hematopoietic expression transgenic mice, revealing evidence multiple subset organ infiltration. Notably, demonstrate STAT5BN642H-driven transformation γδ...
Epigenetic targeting has emerged as an efficacious therapy for hematological cancers. The rare and incurable T-cell prolymphocytic leukemia (T-PLL) is known its aggressive clinical course. Current epigenetic agents such histone deacetylase (HDAC) inhibitors are increasingly used targeted therapy. Through a structure-activity relationship (SAR) study, we developed HDAC6 inhibitor KT-531, which exhibited higher potency in T-PLL compared to other KT-531 displayed strong inhibitory selectivity,...
Histone deacetylases (HDACs) are an attractive therapeutic target for a variety of human diseases. Currently, all four FDA-approved HDAC-targeting drugs nonselective, pan-HDAC inhibitors, exhibiting adverse side effects at doses. Although selective HDAC inhibition has been proposed to mitigate toxicity, the targeted catalytic domains highly conserved. Herein, we describe series rationally designed, conformationally constrained, benzanilide foldamers which selectively bind tunnel HDAC8. The...
Histone deacetylase 6 (HDAC6) has been targeted in clinical studies for anticancer effects due to its role oncogenic transformation and metastasis. Through a second-generation structure–activity relationship (SAR) study, the design, biological evaluation of selective HDAC6 inhibitor NN-390 is reported. With nanomolar potency, >200–550-fold selectivity analogous HDAC isoform functional assays, potent intracellular target engagement, robust cellular efficacy cancer cell lines, first...
A rapid and efficient microwave-assisted synthesis of pomalidomide analogs, improving upon prior methods to accelerate the discovery optimization degraders like clinical candidate ARV-110.
Histone deacetylase 6 (HDAC6) is involved in multiple regulatory processes, ranging from cellular stress to intracellular transport. Inhibition of aberrant HDAC6 activity several cancers and neurological diseases has been shown be efficacious both preclinical clinical studies. While selective targeting pursued as an alternative pan-HDAC drugs, identifying truly molecular templates not trivial. Herein, we report a structure-activity relationship study yielding