Breaking News
February 21, 2019 - Strong social support may reduce cardiovascular disease risk in postmenopausal women
February 21, 2019 - Rapid expansion of interventions could prevent up to 13 million cases of cervical cancer within 50 years
February 21, 2019 - Motif Bio Receives Complete Response Letter From The FDA
February 21, 2019 - Researchers map previously unknown disease in children
February 21, 2019 - A skeptical look at popular diets: Going gluten-free
February 21, 2019 - Podcast: KHN’s ‘What The Health?’ How Safe Are Your Supplements?
February 21, 2019 - Anticipatory signals in eye movements can help measure attentive capacity, learning with greater precision
February 21, 2019 - Evening exercise does not negatively affect sleep, may also reduce hunger
February 21, 2019 - Overweight, obesity in adolescence associated with increased risk of renal cancer later in life
February 21, 2019 - BGU develops new AI platform for monitoring and predicting ALS progression
February 21, 2019 - Researchers discover a new promising target to improve HIV vaccines
February 21, 2019 - Brief Anesthesia in Infancy Does Not Mar Neurodevelopment
February 21, 2019 - Gaming system helps with autism diagnosis
February 21, 2019 - Heart Disease: Six Things Women Should Know
February 21, 2019 - More States Say Doctors Must Offer Overdose Reversal Drug Along With Opioids
February 21, 2019 - Researchers explore case studies focused on industries that kill more people than employed
February 21, 2019 - Only half of GP practice buildings are fit for purpose
February 21, 2019 - Intense exercise, fasting and hormones can enhance waste-protein removal, study shows
February 21, 2019 - Scientists can monitor brain activity to predict epileptic seizures few minutes in advance
February 21, 2019 - Study quantifies hepatic and intestinal mRNA expression of Ugt isoforms in rats
February 21, 2019 - ‘Apple-Shaped’ Body? ‘Pear-Shaped’? Your Genes May Tell
February 21, 2019 - Can we repair the brain? The promise of stem cell technologies for treating Parkinson’s disease
February 21, 2019 - Trump Plan To Beat HIV Hits Rough Road In Rural America
February 21, 2019 - PENTAX Medical introduces new electrosurgical and argon plasma coagulation platforms
February 21, 2019 - Trump plan to beat HIV hits rough road in rural America
February 21, 2019 - Eating blueberries every day could help decrease blood pressure
February 21, 2019 - ‘No Second Chances’ report calls for new measures to combat cardiovascular disease in Australia
February 21, 2019 - Mayo clinic researchers discuss local case studies of leprosy
February 21, 2019 - Scientists demonstrate key role of salt in allergic immune reactions
February 21, 2019 - Experts propose revising the criteria for diagnosis of Parkinson’s disease
February 21, 2019 - The med student and the machine
February 21, 2019 - Hey, Hey! Ho, Ho! Is Striking For School Nurses The Way To Go?
February 21, 2019 - Latest research encourages children to move out and learn through physical activity
February 21, 2019 - Proper oral hygiene and regular visits to dentist can promote heart health
February 21, 2019 - New, versatile technique for remote control of transplanted cells in Parkinson’s
February 21, 2019 - Why melanoma tumors in the brain may be worse?
February 21, 2019 - New project aims to improve lung disease care in Appalachia
February 21, 2019 - Drug increases melanin production in some people with albinism
February 21, 2019 - Over 1 in 3 adults miss the mark on protein, finds study
February 21, 2019 - CymaBay Therapeutics Announces Seladelpar Granted Breakthrough Therapy Designation by the FDA for the Treatment of Primary Biliary Cholangitis
February 21, 2019 - A correlation between obesity and income has only developed in the past 30 years
February 21, 2019 - Baby, then work: An effort to help resident-parents in emergency medicine
February 21, 2019 - Heavy cigarette smoking could damage vision, say researchers
February 21, 2019 - Some drug combinations may be more effective than others for schizophrenic patients
February 21, 2019 - Combination of common antibiotics can eliminate multi-drug resistant E. coli
February 21, 2019 - Number of calls to U.S. Poison Control regarding kratom exposure increased
February 21, 2019 - New computational tool searches for factors that cause specific diseases
February 21, 2019 - New method to assess effectiveness of psychotherapies for social anxiety disorder
February 21, 2019 - New technology measures hormones that influence reproductive health efficiently
February 21, 2019 - Bat influenza viruses could potentially attack the cells of humans and livestock
February 21, 2019 - Immunotherapeutic antibody therapy to kill cancer has now progressed to patient testing
February 21, 2019 - Johns Hopkins scientists find new compound that may prevent reperfusion injury
February 21, 2019 - Researchers develop new way to deliver treatment for cartilage regeneration
February 21, 2019 - Study sheds new light on left ventricular dysfunction in ischemic heart disease
February 21, 2019 - New technique could expedite cancer diagnosis, lead to better patient outcomes
February 21, 2019 - New map of infant brain may aid early diagnosis of autism
February 21, 2019 - Human consciousness depends on the brain’s ability to maintain dynamics of neural activity
February 21, 2019 - Harmony Biosciences Announces File Acceptance Of Its New Drug Application For Pitolisant
February 21, 2019 - Medications could fill treatment gap for adolescents with obesity
February 21, 2019 - New antibiotics are desperately needed: Machine learning could help | News Center
February 21, 2019 - Researchers develop new computer game for dementia carers
February 21, 2019 - University of Dundee partners with Takeda to develop new treatments for tau pathology
February 21, 2019 - Influenza vaccine may be less effective in elderly patients, finds study
February 21, 2019 - Researchers explain why T cells lose their protective ability in inflamed tissues
February 21, 2019 - New optimization method rapidly analyzes nanomedicines for cancer treatment
February 21, 2019 - Viruses in the intestinal tracts can lead to islet autoimmunity and Type 1 diabetes
February 21, 2019 - Link between dietary fatty acid intake and hypertension found to be influenced by diabetes status
February 21, 2019 - FDA Approves Esperoct (turoctocog alfa pegol, N8-GP) for Hemophilia A
February 21, 2019 - ‘Boy erased’—why conversion therapies and ex-gay ministries should be outlawed
February 21, 2019 - Titia de Lange to give annual McCormick Lecture on March 8 | News Center
February 21, 2019 - Study reveals how helper T cells support memory cells to function optimally
February 21, 2019 - Autistic children with co-occurring ADHD have greater adaptive behavior impairments
February 21, 2019 - Elevated levels of key cellular process implicated in intestinal inflammation and IBD
February 20, 2019 - Over Half of Hip Replacements Expected to Last 25 Years
February 20, 2019 - Microscopic eye movements affect how we see contrast
February 20, 2019 - Computer vs. patient: Fighting for residents’ attention | News Center
February 20, 2019 - New “Smart Drug” Shows Promise for Metastatic Triple-Negative Breast Cancer
February 20, 2019 - Researchers develop large-scale window material for high-efficiency PM2.5 capture
February 20, 2019 - Widespread confusion among consumers on food date labels lead to unnecessary discards
February 20, 2019 - Researchers unlock plant’s secret of producing specialized metabolites
Homogenous BTK occupancy assay used in tirabrutinib clinical studies

Homogenous BTK occupancy assay used in tirabrutinib clinical studies

image_pdfDownload PDFimage_print

In a new SLAS Discovery article, Helen Yu and a team of researchers at Gilead Sciences, Inc. (Foster City, CA, USA) present a time-resolved fluorescence resonance energy transfer-based Bruton’s tyrosine kinase (BTK) occupancy assay that can measure target engagement in peripheral blood mononuclear cells (PBMCs) and in lymph-node and bone-marrow samples. The assay provides accurate, quantitative assessment of BTK occupancy and currently is in use in ongoing tirabrutinib clinical studies.

The homogenous BTK occupancy assay’s multiplexed format allows simultaneous measurement of tirabrutinib bound and total BTK levels, reducing clinical sample requirements and avoiding sampling variability observed with traditional single analyte assays.

Yu et al. take advantage of the dual wavelength emission of terbium conjugated anti-BTK antibody to serve as the energy donor for two fluorescent energy acceptors with distinct excitation and emission spectra: G2-streptavidin-bound biotinylated tirabrutinib (detects free BTK) and D2-coupled second anti-BTK antibody that binds to a different BTK epitope (detects total BTK). Additionally, the use of a common fluorescence donor serves to normalize the detection of total and free BTK with respect to each other. The assay is characterized and quantified using full-length purified recombinant human BTK protein and PBMCs derived from healthy volunteers and patients with CLL. The authors demonstrate the assay’s utility using cells derived from samples from patients with CLL and DLBCL.

BTK is expressed in B cells and myeloid cells and plays an essential role in the B-cell receptor (BCR) signaling pathway. Tirabrutinib (GS-4059/ONO-4059) is a second-generation, potent, selective, irreversible BTK inhibitor. It is currently in clinical development as a treatment for chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), and other lymphoid malignancies.

Integrated drug discovery and clinical development programs increasingly emphasize target engagement as a translational approach to inform pharmacodynamic and efficacy assessments. Correlation of tirabrutinib target engagement at the molecular level with pharmacological and phenotypic disease observations is crucial for establishing the appropriate clinical doses.

Posted in: Drug Discovery & Pharmaceuticals | Device / Technology News | Life Sciences News

Tags: Analyte, Antibody, Assay, Blood, Bone, Cell, Chronic Lymphocytic Leukemia, Drug Discovery, Education, Fluorescence, Kinase, Laboratory, Leukemia, Lymphoma, pH, Protein, Receptor, Signaling Pathway, Tyrosine, Wavelength

Tagged with:

About author

Related Articles