A5006284215- Dendrimers and Hyperbranched Polymers
- RNA Interference and Gene Delivery
- Statistical Methods in Clinical Trials
- Nanoparticle-Based Drug Delivery
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- Protein Degradation and Inhibitors
- Estrogen and related hormone effects
- Computational Drug Discovery Methods
- Histone Deacetylase Inhibitors Research
- Pharmacological Receptor Mechanisms and Effects
- Health Systems, Economic Evaluations, Quality of Life
- Science, Research, and Medicine
- Pharmaceutical studies and practices
- Receptor Mechanisms and Signaling
- Hedgehog Signaling Pathway Studies
- Click Chemistry and Applications
AstraZeneca (United States)
2013-2023
Abstract Dual Bcl-2/Bcl-x L inhibitors are expected to deliver therapeutic benefit in many haematological and solid malignancies, however, their use is limited by tolerability issues. AZD4320, a potent dual inhibitor, has shown good efficacy however had dose limiting cardiovascular toxicity preclinical species, coupled with challenging physicochemical properties, which prevented its clinical development. Here, we describe the design development of AZD0466, drug-dendrimer conjugate, where...
Abstract Dual Bcl-2/Bcl-xL inhibitors are expected to deliver therapeutic benefit in many hematological and solid tumors, but their clinical application has been limited by tolerability issues, including thrombocytopenia. AZD4320, a potent dual inhibitor, showed good efficacy encountered dose limiting cardiovascular toxicity preclinical species, had challenging physicochemical properties which prevented its development. Nanocarriers can provide prolonged circulation time, controlled release,...
Abstract A nanoparticle formulation of AZD2811, a selective aurora kinase B inhibitor, is currently under clinical development for the treatment both haematological and solid tumour disease. AZD2811 active derivative prodrug Barasertib (AZD1152) which gave promising activity in elderly AML patients delivered as 7-day infusion (Kantarjian et al, Cancer, 119, 2611-2619, 2013). To address limitations associated with utility other cell cycle inhibitors clinic, has been incorporated into an...
The first-in-patient (FIP) starting dose for oncology agents should be reasonably safe and provide potential therapeutic benefit to the patient. For late-stage patients, this is often based on ICH S9 guidance, which was developed primarily experience with cytotoxic chemotherapeutic using rodent STD