A5031324200- Drug Transport and Resistance Mechanisms
- Protein Degradation and Inhibitors
- Advanced Breast Cancer Therapies
- Dermatology and Skin Diseases
- 14-3-3 protein interactions
- Cancer Treatment and Pharmacology
- Genetic and Kidney Cyst Diseases
- Asthma and respiratory diseases
- HER2/EGFR in Cancer Research
- Pediatric Hepatobiliary Diseases and Treatments
- Hepatitis B Virus Studies
- Ubiquitin and proteasome pathways
- Psoriasis: Treatment and Pathogenesis
- Hepatitis C virus research
- Multiple Myeloma Research and Treatments
Pfizer (United States)
2023-2024
University of North Carolina at Chapel Hill
2024
Janssen (United States)
2022
University of Michigan
2021
Northeast Ohio Medical University
2021
Alliance Pharmaceutical (United States)
2021
TPS1122 Background: ARV-471 is an oral PROTAC ER degrader that binds to and degrades wild-type clinically relevant mutants. directly recruits the ubiquitin-proteasome system degrade ER, whereas selective degraders (SERDs) indirectly cause degradation. In a first-in-human phase 1/2 study, monotherapy was well tolerated showed clinical activity in heavily pretreated patients with ER+/HER2- advanced breast cancer. The 3 dose (200 mg once daily [QD]) chosen due comparable efficacy favorable...
Vepdegestrant (ARV-471) is an oral PROTAC ER degrader that binds E3 ubiquitin ligase and to directly trigger ubiquitination of its subsequent proteasomal degradation. In a first-in-human Phase I/II study, vepdegestrant monotherapy was well tolerated with clinical activity in pretreated patients ER+/HER2- advanced breast cancer. The global, randomized III VERITAC-2 study compares efficacy safety versus fulvestrant adults cancer after treatment CDK4/6 inhibitor plus endocrine therapy....
Guselkumab, a monoclonal antibody that binds to the p19 subunit of interleukin 23, is approved for treatment plaque psoriasis (PsO) and psoriatic arthritis (PsA), palmoplantar pustulosis (PPP), generalized pustular psoriasis, erythrodermic in various countries. The purpose this analysis was develop comprehensive population pharmacokinetic (PK) model guselkumab determine whether PK differs across different disease populations healthy subjects.A nonlinear mixed-effects modelling approach used...
Abstract Background: Vepdegestrant (ARV-471) is an oral PROTAC ER degrader that binds to and degrades wild-type clinically relevant mutants. directly recruits the ubiquitin-proteasome system degrade ER, whereas selective degraders (SERDs) indirectly cause degradation. In a first-in-human phase 1/2 study (NCT04072952), vepdegestrant monotherapy was well tolerated showed clinical activity in heavily pretreated patients with ER+/HER2- advanced breast cancer. The 3 dose (200 mg once daily [QD])...
Aims Serum, liver and urinary bile acids are increased, hepatic transport protein levels decreased in a non‐clinical model of polycystic kidney disease. Similar changes patients with autosomal dominant disease (ADPKD) may predispose them to drug‐induced injury (DILI) drug–drug interactions (DDIs). Systemic coproporphyrin‐I (CP‐I), an endogenous biomarker for OATP1B function MRP2 substrate, is used evaluate OATP1B‐mediated DDI risk humans. In this clinical observational cohort‐comparison...
The prodrug tenofovir alafenamide (TAF) is a first-line antiviral agent for the treatment of chronic hepatitis B infection. TAF activation involves multiple steps, and first step an ester hydrolysis reaction catalyzed by hydrolases. This study was to determine contributions carboxylesterase 1 (CES1) cathepsin A (CatA) in human liver. Our vitro incubation studies showed that both CatA CES1 pH-dependent manner. At their physiologic pH environment, activity (pH 5.2) approximately 1,000-fold...