A5030112757- Cancer Immunotherapy and Biomarkers
- Renal cell carcinoma treatment
- Monoclonal and Polyclonal Antibodies Research
- Economic and Financial Impacts of Cancer
- Biosimilars and Bioanalytical Methods
- Chemical Synthesis and Analysis
- Renal and related cancers
- CAR-T cell therapy research
- Advanced Biosensing Techniques and Applications
- Receptor Mechanisms and Signaling
- Protein purification and stability
- Click Chemistry and Applications
- Glycosylation and Glycoproteins Research
- Chronic Lymphocytic Leukemia Research
- Mass Spectrometry Techniques and Applications
- Synthesis and Characterization of Heterocyclic Compounds
- Protein Kinase Regulation and GTPase Signaling
- Cardiac electrophysiology and arrhythmias
- Muscle Physiology and Disorders
- Synthesis and biological activity
- Genomics and Rare Diseases
- Synthesis and Catalytic Reactions
- Enzyme Structure and Function
- HER2/EGFR in Cancer Research
- Transgenic Plants and Applications
Bristol-Myers Squibb (United States)
2015-2025
Bioanalytical Systems (United States)
2018
United States Military Academy
2007-2014
Merck & Co., Inc., Rahway, NJ, USA (United States)
2014
Bioanalytica (Switzerland)
2013
Bristol-Myers Squibb (Germany)
2013
Provid Pharmaceuticals (United States)
2003-2010
University of California, San Diego
2002-2005
Pennsylvania State University
2004
Sequenom (United States)
2003
A family of novel oligomers based on the anthranilamide nucleus has been prepared and shown to form well-defined secondary structural features. 1H NMR X-ray crystallographic techniques have demonstrated that intramolecular hydrogen bonds play a key role in stabilizing both linear sheet helical conformational forms.
Four constrained cyclic peptides containing the sequence Gly-Asp-Gly-Asp are linked to a central calixarene scaffold (see diagram below) form large surface area for interaction with proteins. These antibody mimics not only bind strongly of cytochrome c but also disrupt its reducing agents.
The neonatal Fc receptor (FcRn) is a key determinant of IgG homeostasis. It binds to the domain in strictly pH-dependent manner and protects from lysosomal degradation. impact FcRn salvage pathway on monoclonal antibody (mAb) pharmacokinetics (PK) has been well established. In this report, set mAbs with wild-type human sequences but different Fab domains were used examine potential vitro binding vivo PK. We surprised find that same shown bind considerable differences both at acidic pH...
Proprotein convertase subtilisin-like/kexin type 9 (PCSK9) regulates LDL cholesterol levels by inhibiting receptor (LDLr)-mediated cellular uptake. We have identified a fragment antigen-binding (Fab) 1D05 which binds PCSK9 with nanomolar affinity. The fully human antibody 1D05-IgG2 completely blocks the inhibitory effects of wild-type and two gain-of-function mutants, S127R D374Y. crystal structure 1D05-Fab bound to reveals that an epitope on catalytic domain includes entire LDLr EGF(A)...
A kinase-anchoring proteins (AKAPs) coordinate cAMP-mediated signaling by binding and localizing cAMP-dependent protein kinase (PKA), using an amphipathic helical docking motif. Peptide disruptors of PKA localization that mimic this helix have been used successfully to assess the involvement in specific pathways. However, these peptides were developed as for type II regulatory subunit (RII) even though both RI RII isoforms can bind AKAPs discrete functions. To evaluate effects each localized...
We have developed an innovative method to remove albumin from plasma/serum samples for the LC-MS/MS quantitation of therapeutic proteins. Different combinations organic solvents and acids were screened their ability plasma serum samples. Removal efficiency was monitored by two signature peptides (QTALVELVK LVNEVTEFAK) albumin. Isopropanol with 1.0% trichloroacetic acid found be most effective combination while retaining protein interest. Our approach compared a commercial depletion kit on...
The mechanism underlying subcutaneous absorption of macromolecules and factors that can influence this process were studied in rats using PEGylated erythropoietins (EPOs) as model compounds. Using a thoracic lymph duct cannulation (LDC) model, we showed EPO was absorbed from the injection site mainly via lymphatic system rats, which is similar to previous reports sheep. After administration, serum exposure reduced by ∼70% LDC animals compared with control animals, most systemically available...
Duchenne muscular dystrophy (DMD) is a genetic muscle disorder that manifests during early childhood and ultimately fatal. Recently approved treatments targeting the cause of DMD are limited to specific subpopulations patients, highlighting need for therapies with wider applications. Pharmacologic inhibition myostatin, an endogenous inhibitor growth produced almost exclusively in skeletal muscle, has been shown increase mass several species, including humans. Taldefgrobep alfa anti-myostatin...
Myostatin is a highly conserved member of the transforming growth factor-β ligand family known to regulate muscle via activation activin receptors. A fusion protein consisting extracellular ligand-binding domain type IIB receptor with Fc portion human immunoglobulin G (ActRIIB-Fc) was used inhibit signaling through this pathway. Here, we study effects in adult, 18-month-old, and orchidectomized mice. Significant enhanced function were observed adult mice treated for 3 days ActRIIB-Fc. The...
The focus of human genetics in recent years has shifted toward identifying genes that are involved the development common diseases such as cancer, diabetes, cardiovascular diseases, and Alzheimer's disease. Because many complex late-onset, frequencies disease susceptibility alleles expected to decrease healthy elderly individuals population at large because their contribution morbidity and/or mortality. To test this assumption, we compared allele 6,500 single-nucleotide polymorphisms (SNPs)...
The neonatal Fc receptor (FcRn) plays a pivotal role in IgG homeostasis, i.e., it salvages antibodies from lysosomal degradation following fluid-phase pinocytosis, thus preventing rapid systemic elimination of IgG. Recombinant therapeutic are typically composed human or humanized sequences, and their biodistribution, tissue distribution, is often studied murine models, although, the effect FcRn on distribution rodents has not been investigated. In this report, an 125I-labeled IgG1 antibody...
BMS-986299 is a first-in-class, NOD-, LRR-, and pyrin-domain containing-3 (NLRP3) inflammasome agonist enhancing adaptive immune T-cell memory responses. This was phase-I (NCT03444753) study that assessed the safety tolerability of intra-tumoral monotherapy (part 1A) in combination 1B) with nivolumab, ipilimumab advanced solid tumors. Reported here are single-center results. 36 patients were enrolled, breast (31%), colorectal (17%), head neck (14%) being more commonly enrolled cancers. Most...
Abstract The first‐in‐human, Phase 1 Study 101 showed antitumor activity and a tolerable safety profile of farletuzumab ecteribulin in Japanese patients with platinum‐resistant ovarian non‐small cell lung cancer. A pharmacometric assessment evaluated pharmacokinetics exposure–response (E‐R) relationships for efficacy to support dose optimization. Patients received 0.3‐1.2 mg/kg intravenously every 3 weeks. (PK) model was developed used E‐R analyses. Efficacy assessed via tumor response known...
Objective: Characterize the population pharmacokinetics (PPK) of repotrectinib in adults and pediatrics with a model to account for time-changing clearance resulting from drug induced auto-induction.Methods: Repotrectinib is tyrosine kinase inhibitor being developed treatment harboring ROS1 positive non small cell lung cancer (NSCLC) adult or pediatric NTRK solid tumors. A dataset (with healthy volunteers patients) including 7 studies (N&#3f620) 1 study (N&#3f24) were available...
Objectives: Repotrectinib is a tyrosine kinase inhibitor approved in the US for treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC and currently being developed pediatric NTRK-positive solid tumors. Exposure - response (E-R) models were selected key efficacy endpoints (OR: objective rate PFS: progression-free survival) clinical safety (Gr2+ dizziness : ≥ Grade 2 dizziness, DRDI: dose reduction interruption due to AEs) support benefit-risk assessment...
Localization of protein kinase A (PKA) via A-kinase-anchoring proteins (AKAPs) is important for cAMP responsiveness in many cellular systems, and evidence suggests that AKAPs play an role cardiac signaling. To test the importance AKAP-mediated targeting PKA on function, we designed a cell-permeable peptide, which termed trans-activator transcription (TAT)-AKAD TAT-conjugated disruptor, using binding region AKAP10 tested effects this peptide isolated myocytes Langendorff-perfused mouse...