A5035816736- Lung Cancer Treatments and Mutations
- Gastrointestinal Tumor Research and Treatment
- Gastric Cancer Management and Outcomes
- Platelet Disorders and Treatments
- Hepatocellular Carcinoma Treatment and Prognosis
- Pharmacogenetics and Drug Metabolism
- Renal cell carcinoma treatment
- Lung Cancer Diagnosis and Treatment
- PI3K/AKT/mTOR signaling in cancer
- Computational Drug Discovery Methods
- Prostate Cancer Treatment and Research
- Renal and related cancers
- Sarcoma Diagnosis and Treatment
- Statistical Methods in Clinical Trials
- Receptor Mechanisms and Signaling
- Synthesis and biological activity
- Drug Transport and Resistance Mechanisms
- Liver physiology and pathology
- Cell Adhesion Molecules Research
- Hormonal and reproductive studies
- Analytical Chemistry and Chromatography
- Ferroptosis and cancer prognosis
- Mass Spectrometry Techniques and Applications
- Cancer, Lipids, and Metabolism
- Lung Cancer Research Studies
AstraZeneca (United Kingdom)
2013-2025
Pfizer (United States)
2007-2023
AstraZeneca (United States)
2023
AstraZeneca (Switzerland)
2020
Newcastle University
2013
Implementation of in vitro assays that correlate with vivo human pharmacokinetics (PK) would provide desirable preclinical tools for the early selection therapeutic monoclonal antibody (mAb) candidates minimal non-target-related PK risk. Use these minimizes likelihood mAbs unfavorable be advanced into costly and clinical development. In total, 42 varying isotype soluble versus membrane targets were tested studies. MAb physicochemical properties assessed by measuring non-specific interactions...
Abstract Purpose: Papillary renal cell carcinoma (PRCC) is the second most common cancer of kidney and carries a poor prognosis for patients with nonlocalized disease. The HGF receptor MET plays central role in PRCC aberrations, either through mutation, copy number gain, or trisomy chromosome 7 occurring majority cases. development effective therapies has been hampered part by lack available preclinical models. We determined pharmacodynamic antitumor response selective inhibitor AZD6094 two...
Abstract Continued androgen receptor (AR) expression and signaling is a key driver in castration-resistant prostate cancer (CRPC) after classical ablation therapies have failed, therefore remains target for the treatment of progressive disease. Here, we describe biological characterization AZD3514, an orally bioavailable drug that inhibits androgen-dependent -independent AR signaling. AZD3514 modulates through two distinct mechanisms, inhibition ligand-driven nuclear translocation...
Abstract Quantitative systems pharmacology (QSP) approaches have been increasingly applied in the pharmaceutical since landmark white paper published 2011 by a National Institutes of Health working group brought attention to discipline. In this perspective, we discuss QSP context other modeling and highlight impact across various stages drug development therapeutic areas. We challenges field as well future opportunities.
While the treatment of gastrointestinal stromal tumors (GISTs) has been revolutionized by application targeted tyrosine kinase inhibitors capable inhibiting KIT-driven proliferation, diverse mutations to this drive resistance established therapies. Here we describe identification potent pan-KIT mutant that can be dosed without being limited tolerability issues seen with multitargeted agents. This effort focused on and optimization an existing scaffold through use structure-based design....
1. In vivo clearance predictions from in vitro assays require scaling factors to relate the concentrations of hepatocytes or microsomal protein intact liver.2. The aims were measure variability for Wistar rat and beagle dog which literature is particularly scarce determine any sex differences.3. Scaling determined by comparing cytochrome P450 (P450) content microsomes against fresh liver homogenate. use homogenate recommended as freezing can increase contamination affect assay.4. Meangeo...
The relationship between rat pharmacokinetics and physicochemical parameters [the partition coefficient octanol buffer at pH 7.4 (log D<sub>(7.4)</sub>) p<i>K</i><sub>a</sub>] was studied for a series of tetrahydropyran compounds. Sixteen compounds ranging in log D<sub>(7.4)</sub> 0.1 to 1.8 were administered intravenously rats, the pharmacokinetic determined from blood concentration time curves. Across series, weak correlation observed clearance, suggesting that values less than 0.5...
Trastuzumab deruxtecan (T-DXd; DS-8201; ENHERTU®) is a human epithelial growth factor receptor 2 (HER2)-directed antibody drug conjugate (ADC) with demonstrated antitumor activity against range of tumor types. Aiming to understand the relationship between antigen expression and downstream efficacy outcomes, T-DXd was administered in tumor-bearing mice carrying NCI-N87, Capan-1, JIMT-1, MDA-MB-468 xenografts, characterized by varying HER2 levels. Plasma pharmacokinetics (PK) total antibody,...
AZD3229 demonstrates pan-KIT/PDGFRα activity in several preclinical models and is a promising agent for the treatment of GIST.
Abstract Osimertinib is a third-generation, irreversible, oral EGFR tyrosine kinase inhibitor (TKI) recommended as first-line treatment for patients with locally advanced/metastatic mutation–positive (EGFRm) non–small cell lung cancer (NSCLC). However, MET amplification/overexpression common acquired osimertinib resistance mechanism. Savolitinib an oral, potent, and highly selective MET-TKI; preliminary data suggest that combining savolitinib may overcome MET-driven resistance. A...
The emergence of secondary mutations is a cause resistance to current KIT inhibitors used in the treatment patients with gastrointestinal stromal tumors (GIST). AZD3229 selective inhibitor wild-type and wide spectrum primary seen GIST. objective this analysis establish pharmacokinetic-pharmacodynamic (PKPD) relationship range mouse GIST tumor models harboring mutations, benchmark against other inhibitors.A PKPD model was developed for linking plasma concentrations inhibition phosphorylated...
Savolitinib (AZD6094, HMPL-504, volitinib) is an oral, potent, and highly MET receptor TK inhibitor. This series of studies aimed to develop a pharmacokinetic-pharmacodynamic (PK/PD) model link inhibition phosphorylation (pMET) by savolitinib with anti-tumour activity.Cell line-derived xenograft (CDX) experiments using human lung cancer (EBC-1) gastric (MKN-45) cells were conducted in athymic nude mice variety doses schedules savolitinib. Tumour pMET changes growth calculated after 28 days....
Aim:To investigate the feasibility, and patient/psychiatrist acceptability, of an SMS text messaging system reminding patients receiving quetiapine to take their medication.Methods:8-12(mean:9.4) week, non-interventional, psychiatrist assessed, pilot study 27 outpatients (mean age[range]: 35.3[19-57] years). Patients were asked reply messages sent twice daily cellular phone remind them medication (morning) enquire about well-being (evening). Patients' response (morning-yes/no;...