Victoria Head
A5057650441- Synthesis and biological activity
- Bioactive Compounds and Antitumor Agents
- Pharmacological Effects of Natural Compounds
- Sphingolipid Metabolism and Signaling
- Enzyme function and inhibition
- Biochemical and Molecular Research
- Cancer therapeutics and mechanisms
- Phytochemicals and Antioxidant Activities
- Ion channel regulation and function
- Protein Kinase Regulation and GTPase Signaling
- Medical Imaging and Pathology Studies
- Carbohydrate Chemistry and Synthesis
- Cancer-related Molecular Pathways
- Phonocardiography and Auscultation Techniques
- Asthma and respiratory diseases
- Ubiquitin and proteasome pathways
- Ion Channels and Receptors
- Parathyroid Disorders and Treatments
- Protein Tyrosine Phosphatases
- Receptor Mechanisms and Signaling
- Heterotopic Ossification and Related Conditions
Novartis (Switzerland)
2017-2022
Novartis Institutes for BioMedical Research
2017-2022
Novartis (United Kingdom)
2014-2020
Covalent inhibitors of KRASG12C have shown antitumor activity against advanced/metastatic KRASG12C-mutated cancers, though resistance emerges and additional strategies are needed to improve outcomes. JDQ443 is a structurally unique covalent inhibitor GDP-bound that forms novel interactions with the switch II pocket. potently inhibits KRASG12C-driven cellular signaling demonstrates selective antiproliferative in cell lines, including those G12C/H95 double mutations. In vivo, induces AUC...
A high throughput screening campaign identified 5-(2-chlorophenyl)indazole compound 4 as an antagonist of the transient receptor potential A1 (TRPA1) ion channel with IC50 = 1.23 μM. Hit to lead medicinal chemistry optimization established SAR around indazole ring system, demonstrating that a trifluoromethyl group at 2-position phenyl in combination various substituents 6-position greatly contributed improvements vitro activity. Further resulted identification 31, potent and selective TRPA1...
Intracellular Ca2+ and cAMP typically cause opposing effects on airway smooth muscle contraction. Receptors that stimulate these pathways are therapeutic targets in asthma chronic obstructive pulmonary disease. However, the interactions between different G protein-coupled receptors (GPCRs) evoke signals human bronchial cells (hBASMCs) poorly understood. We measured cultures of fluo-4-loaded hBASMCs alongside measurements intracellular using mass spectrometry or [3H]-adenine labeling....
Abstract RAS is the most frequently mutated oncogene in cancer. KRAS G12C mutations are prevalent lung adenocarcinoma (~13%) and colorectal (~4%), occur less commonly other solid tumor malignancies. First generation KRASG12C inhibitors show anti-tumor activity early phase clinical trials. However, emergence of resistance, mediated at least part by gene that disrupt inhibitor binding reactivation downstream pathways, limit duration response. Here we report identification JDQ443 (NVP-JDQ443),...
<div>Abstract<p>Covalent inhibitors of KRAS<sup>G12C</sup> have shown antitumor activity against advanced/metastatic <i>KRAS<sup>G12C</sup></i>-mutated cancers, though resistance emerges and additional strategies are needed to improve outcomes. JDQ443 is a structurally unique covalent inhibitor GDP-bound that forms novel interactions with the switch II pocket. potently inhibits KRAS<sup>G12C</sup>-driven cellular signaling...
<div>Abstract<p>Covalent inhibitors of KRAS<sup>G12C</sup> have shown antitumor activity against advanced/metastatic <i>KRAS<sup>G12C</sup></i>-mutated cancers, though resistance emerges and additional strategies are needed to improve outcomes. JDQ443 is a structurally unique covalent inhibitor GDP-bound that forms novel interactions with the switch II pocket. potently inhibits KRAS<sup>G12C</sup>-driven cellular signaling...
Supplementary Data from Discovery, Preclinical Characterization, and Early Clinical Activity of JDQ443, a Structurally Novel, Potent, Selective Covalent Oral Inhibitor KRAS<sup>G12C</sup>
Supplementary Data from Discovery, Preclinical Characterization, and Early Clinical Activity of JDQ443, a Structurally Novel, Potent, Selective Covalent Oral Inhibitor KRAS<sup>G12C</sup>
Supplementary Data from Discovery, Preclinical Characterization, and Early Clinical Activity of JDQ443, a Structurally Novel, Potent, Selective Covalent Oral Inhibitor KRAS<sup>G12C</sup>
Supplementary Data from Discovery, Preclinical Characterization, and Early Clinical Activity of JDQ443, a Structurally Novel, Potent, Selective Covalent Oral Inhibitor KRAS<sup>G12C</sup>
Supplementary Data from Discovery, Preclinical Characterization, and Early Clinical Activity of JDQ443, a Structurally Novel, Potent, Selective Covalent Oral Inhibitor KRAS<sup>G12C</sup>
Supplementary Data from Discovery, Preclinical Characterization, and Early Clinical Activity of JDQ443, a Structurally Novel, Potent, Selective Covalent Oral Inhibitor KRAS<sup>G12C</sup>