A5014135423- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Peptidase Inhibition and Analysis
- Click Chemistry and Applications
- Epigenetics and DNA Methylation
- Phytochemicals and Antioxidant Activities
- Computational Drug Discovery Methods
- Cholinesterase and Neurodegenerative Diseases
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Pancreatic and Hepatic Oncology Research
- Tannin, Tannase and Anticancer Activities
- Natural Antidiabetic Agents Studies
- Food Science and Nutritional Studies
- Glioma Diagnosis and Treatment
- Estrogen and related hormone effects
- Free Radicals and Antioxidants
- Ubiquitin and proteasome pathways
- Synthesis and biological activity
- Synthetic Organic Chemistry Methods
- Chronic Lymphocytic Leukemia Research
- Synthesis and Biological Evaluation
- Cytokine Signaling Pathways and Interactions
- Melanoma and MAPK Pathways
United Arab Emirates University
2024-2025
University of Toronto
2019-2023
Canadian Celiac Association
2020
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...
Alzheimer's disease is a neurodegenerative disorder that impairs neurocognitive functions. Acetylcholinesterase, Butyrylcholinesterase, Monoamine Oxidase B, Beta-Secretase, and Glycogen Synthase Kinase Beta play central roles in its pathogenesis. Current medications primarily inhibit AChE but fail to halt or reverse progression due the multifactorial nature of Alzheimer's. This underscores necessity developing multi-target ligands for effective treatment. study investigates potential...
Cognitive dysfunction in Alzheimer’s disease results from a complex interplay of various pathological processes, including the dysregulation key enzymes such as acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and monoamine oxidase B (MAO-B). This study proposes designs series novel molecules derived 8-hydroxyquinoline (Azo-8HQ) potential multi-target lead candidates for treating AD. An exhaustive silico analysis was conducted, encompassing docking studies, ADMET analysis, density...
Thyroid hormone (TH) signaling plays a major role in the development, energy homeostasis, and metabolism of most tissues. Recent observations have identified THs as drivers prostate cancer (PCa) tumor development progression. We reported that T3-scavenger protein μ-crystallin (CRYM) regulates progression PCa this involved crosstalk with androgen receptor (AR) signaling. However, mechanisms remain incompletely understood. Here, we explored thyroid β (TRβ), which is main effector TH signaling,...
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive, incurable cancer with a 20% 1 year survival rate. While standard-of-care therapy can prolong life in small fraction of cases, PDAC inherently resistant to current treatments, and novel therapies are urgently required. Histone deacetylase (HDAC) inhibitors effective killing pancreatic cells vitro studies, although there few clinical studies investigating combination including HDAC inhibitors, no drug or has been approved for the...
Histone deacetylases (HDACs) have emerged as powerful epigenetic modifiers of histone/non-histone proteins via catalyzing the deacetylation ε-N-acetyl lysines. The dysregulated activity these Zn2+-dependent hydrolases has been broadly implicated in disease, notably cancer. Clinically, recurring dose-limiting toxicities first-generation HDACi sparked a paradigm shift toward safer isoform-specific molecules. With pervasive roles aggressive diseases, there remains need for novel approaches to...
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
The HDAC inhibitor 4-tert-butyl-N-(4-(hydroxycarbamoyl)phenyl)benzamide (AES-350, 51) was identified as a promising preclinical candidate for the treatment of acute myeloid leukemia (AML), an aggressive malignancy with meagre 24% 5-year survival rate. Through screening low-molecular-weight analogues derived from previously discovered novel inhibitor, AES-135, compound 51 demonstrated greater isoform selectivity, higher cytotoxicity in MV4-11 cells, improved therapeutic window, and more...
Angiogenesis is a crucial process in the growth and proliferation of cancer, enabling tumor through formation new vasculature supply nutrients oxygen to growing malignant cells. This disease-promoting can be targeted inhibition tyrosine kinase enzymes.