A5005390105- Protein Degradation and Inhibitors
- Advanced Breast Cancer Therapies
- Computational Drug Discovery Methods
- Cancer-related Molecular Pathways
- Chronic Lymphocytic Leukemia Research
- Cancer Mechanisms and Therapy
- Ovarian cancer diagnosis and treatment
- PARP inhibition in cancer therapy
- Microtubule and mitosis dynamics
- Synthesis and biological activity
- Prostate Cancer Treatment and Research
- Pharmacovigilance and Adverse Drug Reactions
- Tuberculosis Research and Epidemiology
- thermodynamics and calorimetric analyses
- DNA Repair Mechanisms
- Click Chemistry and Applications
- Phytochemical compounds biological activities
- Healthcare cost, quality, practices
- Virus-based gene therapy research
- Nanoparticle-Based Drug Delivery
- Ubiquitin and proteasome pathways
- Proteins in Food Systems
- PI3K/AKT/mTOR signaling in cancer
- Advanced Drug Delivery Systems
- Health Systems, Economic Evaluations, Quality of Life
University of South Australia
2016-2024
University of Newcastle Australia
2024
Cyclin D dependent kinases (CDK4 and CDK6) regulate entry into S phase of the cell cycle are validated targets for anticancer drug discovery. Herein we detail discovery a novel series 4-thiazol-N-(pyridin-2-yl)pyrimidin-2-amine derivatives as highly potent selective inhibitors CDK4 CDK6. Medicinal chemistry optimization resulted in 83, an orally bioavailable inhibitor molecule with remarkable selectivity. Repeated oral administration 83 caused marked inhibition tumor growth MV4-11 acute...
Abstract Background Cyclin-dependent kinase 9 (CDK9) stimulates oncogenic transcriptional pathways in cancer and CDK9 inhibitors have emerged as promising therapeutic candidates. Methods The activity of an orally bioavailable inhibitor, CDKI-73, was evaluated prostate cell lines, a xenograft mouse model, patient-derived tumor explants organoids. Expression clinical specimens by mining public datasets immunohistochemistry. Effects CDKI-73 on cells were determined cell-based assays, molecular...
A simple and cost-effective UV spectrophotometric method was developed validated for the routine analysis of molnupiravir (MLP) using 10% (v/v) methanol as solvent. The absorption maximum (λmax) determined to be 238 nm. according ICH guidelines, results demonstrated its suitability, specificity, linearity, accuracy, precision, sensitivity, ruggedness, robustness. showed a linear response within concentration range 2-20 µg/ml, with correlation coefficient (R²) 0.9972. expressed % recovery,...
Background and Purpose Cyclin D‐dependent kinases 4 6 (CDK4/6) are crucial regulators of the G1 to S phase transition cell cycle actively pursued as therapeutic targets in cancer. We sought discover a novel series orally bioavailable highly selective small molecule inhibitors CDK4/6. Experimental Approach The discovery pharmacological optimization for potency, selectivity drug properties were achieved by iterative chemical synthesis, biochemical screening against panel kinases, cell‐based...
Cytarabine (Ara-C) is a first line clinical therapeutic agent for treatment of acute myeloid leukemia (AML). However, this therapy limited due to high rate resistance and relapse. Recent research has revealed that the poor prognosis Ara-C in AML were associated with its abnormally activated MAPK pathways. In study, we showed strong synergistic effect either our Mnk inhibitor (MNKI-8e) or short hairpin RNA (shRNA) mediated knockdown Mnks MV4-11 cells. We investigated underlying mechanisms...
SETTING: Active pharmacovigilance (PV) is recommended for TB programmes, notably multidrug-resistant (MDR-TB) patients treated with new drugs. Launched the support of UNITAID in April 2015, endTB (Expand New Drug markets TB) facilitated treatment bedaquiline (BDQ) and/or delamanid >2600 17 countries, and contributed to creation a central PV unit (PVU). OBJECTIVE: To explain PVU process by describing serious adverse events (SAEs) experienced who received BDQ-containing regimens. DESIGN:...
The global burden of cancer necessitates rapid and ongoing development effective therapies. One promising approach in this context is the repurposing existing non-cancer drugs for indications. A key to selecting cellular targets against which identify novel repurposed pre-clinical analysis. Protein kinases are highly sought-after anticancer drug since dysregulation hallmark cancer. To potential kinase-targeted candidates from portfolio therapeutics, we used combined silico vitro approaches,...
Aberrant expression of eukaryotic translation initiation factor 4E (eIF4E) is common in many types cancer including acute myeloid leukaemia (AML). Phosphorylation eIF4E by MAPK-interacting kinases (Mnks) essential for the eIF4E-mediated oncogenic activity. As such, pharmacological inhibition Mnks can be an effective strategy treatment cancer.A series N-phenyl-4-(1H-pyrrol-3-yl)pyrimidin-2-amine derivatives was designed and synthesised. The Mnk inhibitory activity these as well their...
In 2015, the initiative Expand New Drug Markets for TB (endTB) began, with objective of reducing barriers to access new and repurposed drugs. Here we describe major implementation challenges encountered in 17 endTB countries. We provide insights on how national programmes other stakeholders can scale-up programmatic use drugs, while building scientific evidence about their safety efficacy. For any drug or diagnostic, multiple market slow pace scale-up. During 2015–2019, was successful...
<p class="first" dir="auto" id="d226862e116">Drug repurposing is a potentially cheap, rapid and authentic aspect of drug development at time when the need for new therapeutic solutions high. Issues such as scale, diversity, complexity associated with are areas well covered elsewhere. The interwoven issues pleiotropy, including serendipitous discovery pleiotropy less described we believe it fundamental to our understanding repurposing. id="d226862e118">Pleiotropy has been cornerstone in...
<p class="first" dir="auto" id="d4833686e102">The issue of taking drugs from laboratory into clinical trials or practice can be long, expensive and arduous. As seen during the pandemic where there was additional urgency, together with often a lack funding, little pharmacology input choice drug dose, potted engagement multidisciplinary skillsets, Australia spent lot funds human resources on repurposed medicines research vaccine that never provided any therapeutics available for use....
Drug repurposing has potential to improve outcomes for high-grade serous ovarian cancer (HGSOC). Repurposing drugs with PARP family binding activity may produce cytotoxic effects through the multiple mechanisms of including DNA repair, cell-cycle regulation, and apoptosis. The aim this study was determine existing that have can be repurposed treatment HGSOC.
Acute myeloid leukaemia (AML) affects predominantly elderly people and has an incidence of 1% all cancers 2% cancer deaths. Despite using intensive chemotherapy allogeneic stem cell transplantation, the treatment options for AML remain open innovation. Thus, there is a need to explore alternative therapies such as less toxic targeted in AML. Aurora A kinase well-established target various cancers, including This plays pivotal role cell-division cycle, particularly different stages mitosis,...
Background and Purpose: Drug repurposing has potential to improve the care for treatment resistant high-grade serous ovarian cancer (HGSOC). We hypothesised that broadly targeting PARP drug would elicit cytotoxic responses in HGSOC through multiple biological processes. Experimental Approach: in-silico ligand-based virtual screening BLAZE was used identify drugs with PARP-binding activity. The list refined by dosing known cytotoxicity, lipophilicity, teratogenicity, side effects. highest...
Abstract Cyclin D dependent kinases CDK4 & CDK6 are crucial regulators of the G1 to S phase transition cell cycle. The facts that myriad cancer types show aberrance in INK4-CDK4/6-cyclin D-Rb-E2F pathway, rapidly emerging positive clinical data pharmacological inhibitors have validated CDK4/6 as anticancer drug targets. As first commercialized CDK inhibitor, palbociclib combination with letrozole or fulvestrant has received regulatory approval for treatment breast cancer. This represents...