A5010162365- Ubiquitin and proteasome pathways
- Lymphoma Diagnosis and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Mass Spectrometry Techniques and Applications
- Microtubule and mitosis dynamics
- Biosimilars and Bioanalytical Methods
- Chronic Lymphocytic Leukemia Research
- Analytical Chemistry and Chromatography
- Neuroblastoma Research and Treatments
- Neurofibromatosis and Schwannoma Cases
- HER2/EGFR in Cancer Research
- Microfluidic and Capillary Electrophoresis Applications
- Advanced Biosensing Techniques and Applications
- Biosensors and Analytical Detection
- Glioma Diagnosis and Treatment
- Protein Degradation and Inhibitors
- Cell Adhesion Molecules Research
- Analytical chemistry methods development
- Cancer-related Molecular Pathways
- Pharmacogenetics and Drug Metabolism
- Innovative Microfluidic and Catalytic Techniques Innovation
- Peptidase Inhibition and Analysis
- Viral Infectious Diseases and Gene Expression in Insects
- 14-3-3 protein interactions
- Statistical Methods in Clinical Trials
Takeda (United States)
2010-2025
AstraZeneca (United States)
2021-2024
Takeda (Japan)
2014-2024
Millennium Engineering and Integration (United States)
2004-2021
Cincinnati Children's Hospital Medical Center
2012
Nationwide Children's Hospital
2012
Institute of Predictive and Personalized Medicine of Cancer
2012
The Ohio State University
2012
University of Michigan
1995-1998
SUMOylation is a reversible post-translational modification that regulates protein function through covalent attachment of small ubiquitin-like modifier (SUMO) proteins. The process SUMOylating proteins involves an enzymatic cascade, the first step which entails activation SUMO ATP-dependent catalyzed by SUMO-activating enzyme (SAE). Here, we describe identification TAK-981, mechanism-based inhibitor SAE forms SUMO–TAK-981 adduct as inhibitory species within catalytic site. Optimization...
The surge in the clinical use of therapeutic antibodies has reshaped landscape pharmaceutical therapy for many diseases, including rare and challenging conditions. However, administration exogenous biologics could potentially trigger unwanted immune responses such as generation anti-drug (ADAs). Real-world experiences have illuminated clear correlation between ADA occurrence unsatisfactory outcomes well immune-related adverse events. By retrospectively examining research involving...
Patients with neurofibromatosis type 1 (NF1) develop malignant peripheral nerve sheath tumors (MPNST), which are often inoperable and do not respond well to current chemotherapies or radiation. The goal of this study was use comprehensive gene expression analysis identify novel therapeutic targets.Nerve Schwann cells and/or their precursors the tumorigenic cell types in MPNST because loss NF1 gene, encodes RasGAP protein neurofibromin. Therefore, we created a transgenic mouse model,...
Renal impairment (RI) is a major complication of multiple myeloma (MM). This study aimed to characterize the single-dose pharmacokinetics (PK) oral proteasome inhibitor, ixazomib, in cancer patients with normal renal function [creatinine clearance (CrCl) ≥90 ml/min; n = 20), severe RI (CrCl <30 14), or end-stage disease requiring haemodialysis (ESRD; 7). PK and adverse events (AEs) were assessed after single 3 mg dose ixazomib. Ixazomib was highly bound plasma proteins (~99%) all groups....
A novel liquid chromatography/tandem mass spectrometry (LC/MS/MS)-based depletion method for measuring compound partitioning between human plasma and red blood cells (RBC) in a drug discovery environment is presented. Conventionally, RBC determined by separate measurements of concentrations equilibrating whole or using standards prepared their respective matrices, i.e., lysates. The process very tedious, labor-intensive, difficult to automate. In addition, interferences from the heme other...
In the ongoing quest for ever more rapid techniques to quantify small organic molecules, we have evaluated a chemiluminescent nitrogen detector (CLND) as universal quantitation tool nitrogen-containing molecules. By flow injection analysis (FIA) and in conjunction with reversed-phase (RP) chromatography using gradient elution, CLND produced linear response from 25 6400 pmol of that was equivalent set chemically structurally diverse compounds. Over entire range, absolute exhibited an average...
Aim The aim of the present study was to characterize pharmacokinetics oral proteasome inhibitor, ixazomib, in patients with solid tumours and moderate or severe hepatic impairment, provide posology recommendations. Methods Eligible adults advanced malignancies for which no further effective therapy available received a single dose ixazomib on day 1 pharmacokinetic cycle; normal function, impairment 4 mg, 2.3 mg 1.5 respectively. Blood samples single‐dose characterization were collected over...
The 18th Workshop on Recent Issues in Bioanalysis (18th WRIB) took place San Antonio, TX, USA May 6-10, 2024. Over 1100 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest bioanalysis. WRIB included 3 Main Workshops 7 Specialized that together spanned 1 week allow an exhaustive thorough coverage all major issues bioanalysis biomarkers, immunogenicity, gene therapy, cell therapy...
Biotherapeutics have demonstrated remarkable therapeutic efficacy across a wide range of diseases; however, their clinical application is often hindered by the development anti-drug antibodies (ADAs). Traditionally, ADA monitoring has relied on ligand-binding assays (LBAs) such as enzyme-linked immunosorbent (ELISA) or electrochemiluminescence (ECLIA). Although effective, these methods require multiple washing and incubation steps, extending data generation time to several hours even days....
The microdosing strategy allows for early assessment of human pharmacokinetics new chemical entities using more limited safety requirements than those requisite a conventional phase I program. current choice evaluating is accelerator mass spectrometry (AMS) due to its ultrasensitivity detecting radiotracers. However, the AMS technique still expensive be used routinely and requires preparation radiolabeled compounds. This report describes feasibility study with liquid chromatography-tandem...
This article describes the discovery of a series potent inhibitors Polo-like kinase 1 (PLK1). Optimization this benzolactam-derived chemical produced an orally bioavailable inhibitor PLK1 (12c, MLN0905). In vivo pharmacokinetic-pharmacodynamic experiments demonstrated prolonged mitotic arrest after oral administration 12c to tumor bearing nude mice. A subsequent efficacy study in mice achieved growth inhibition or regression human colon (HT29) xenograft model.
The 2017 11th Workshop on Recent Issues in Bioanalysis (11th WRIB) took place Los Angeles/Universal City, California 3–7 April with participation of close to 750 professionals from pharmaceutical/biopharmaceutical companies, biotechnology contract research organizations and regulatory agencies worldwide. WRIB was once again a 5-day, weeklong event – full immersion week bioanalysis, biomarkers immunogenicity. As usual, it specifically designed facilitate sharing, reviewing, discussing...
The 14th edition of the Workshop on Recent Issues in Bioanalysis (14th WRIB) was held virtually June 15-29, 2020 with an attendance over 1000 representatives from pharmaceutical/biopharmaceutical companies, biotechnology contract research organizations, and regulatory agencies worldwide. WRIB included three Main Workshops, seven Specialized Workshops that together spanned 11 days order to allow exhaustive thorough coverage all major issues bioanalysis, biomarkers, immunogenicity, gene...
Characterizing in vivo cellular kinetics and biodistribution of chimeric antigen receptor T (CAR-T) cells is critical for toxicity assessment, nonclinical clinical efficacy studies. To date, the standardized assay to characterize CAR-T cell distribution, expansion, contraction, persistence profiles not readily available. overcome this limitation increase comparability among studies, we have established a universal protocol analysis. We duplexing ddPCR transgene reference gene normalize...
The 16th Workshop on Recent Issues in Bioanalysis (16th WRIB) took place Atlanta, GA, USA September 26-30, 2022. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest bioanalysis. WRIB included 3 Main Workshops 7 Specialized that together spanned 1 week order allow exhaustive thorough coverage all major issues bioanalysis, biomarkers, immunogenicity, gene therapy, cell therapy...
In this work, a novel open-tubular column (OTC) capillary electrochromatography (CEC) system has been coupled to an on-line ion trap storage/reflectron time-of-flight mass spectrometer for ultrafast peptide mixture analysis. Reversed-phase OTCs prepared by the sol-gel process were coated with amine, which greatly enhanced electroosmotic flow in acidic buffer solution and considerably reduced nonspecific adsorption between peptides wall. A six-peptide could be separated baseline within 3 min...
An ion trap storage (IT)/reflectron time-of-flight mass spectrometer (reTOFMS) has been coupled to capillary electrophoresis (CE) via a sheathless microelectrospray ionization method. This hybrid proved be rapid and sensitive detector for CE, where spectra could acquired at speed sufficient maintain the high-resolution capabilities of CE separations. The nonscanning property analyzer can provide full range spectral acquisition up 25 spectra/s with data system developed in our laboratory. For...
Purpose: Pediatric glioblastoma multiforme (pGBM) is a highly aggressive tumor in need of novel therapies. Our objective was to demonstrate the therapeutic efficacy MLN8237 (alisertib), an orally available selective inhibitor Aurora A kinase (AURKA), and evaluate which vitro model system (monolayer or neurosphere) can predict vivoExperimental Design: AURKA mRNA expressions were screened with qRT-PCR. In antitumor effects examined three matching pairs monolayer neurosphere lines established...
Plasma stability assessment under physiological temperature is an essential step for developing and optimizing antibody drug conjugate (ADC) molecules, especially those with cleavable linkers. The of plasma often requires monitoring multiple analytes using a combination bioanalytical assays free payloads, conjugated payloads (or antibodies), total antibodies, that have migrated from antibodies to constituent proteins. Bioanalytical are needed in early discovery quickly screen diverse ADC...
The integration of ligand-binding assay and LC–MS/MS (immunocapture-LC–MS) has unleashed the combined advantages both powerful techniques for addressing ever increasing bioanalytical challenges biotherapeutics biomarker assays. highly specific, selective sensitive characteristics immunocapture-LC–MS-based assays have enabled determination biomarkers in biomatrices with ease method development, less requirements on key reagents as well structural specificity endogenous engineered...
Diffuse large B-cell lymphoma (DLBCL) is the most common of non-Hodgkin lymphomas, accounting for up to 30% all newly diagnosed cases. Current treatment options this disease are effective, but not always curative; therefore, experimental therapies continue be investigated. We have discovered an experimental, potent, and selective small-molecule inhibitor PLK1, MLN0905, which inhibits cell proliferation in a broad range human tumor cells including DLBCL lines. In our report, we explored...