A Human Whole Blood Model for Screening Potential Vesicant Antagonists

2002 ◽  
Author(s):  
Michael D. Blaha ◽  
David A. DuBose
Keyword(s):  
Whole Blood ◽  
Human Whole Blood

scholarly journals Monocyte CD163 and CD36 Expression in Human Whole Blood and Isolated Mononuclear Cell Samples: Influence of Different Anticoagulants

2006 ◽  
Vol 13 (6) ◽  
pp. 704-707 ◽  
Author(s):  
Marcin Moniuszko ◽  
Krzysztof Kowal ◽  
Malgorzata Rusak ◽  
Miroslawa Pietruczuk ◽  
Milena Dabrowska ◽  
...  
Keyword(s):  
Density Gradient ◽  
Mononuclear Cell ◽  
Whole Blood ◽  
Cell Isolation ◽  
Scavenger Receptors ◽  
Published Data ◽  
Healthy Individuals ◽  
Human Whole Blood ◽  
Cd36 Expression

ABSTRACT We investigated whether the choice of anticoagulant or the application of density gradient mononuclear cell isolation may account for conflicting published data regarding the levels of the scavenger receptors' expression in healthy individuals. We demonstrate that the detection of CD163, but not CD36, differs dramatically among the methods.

scholarly journals Isolation and characterization of circulating pro-vascular progenitor cell subsets from human whole blood samples

2021 ◽  
Vol 2 (1) ◽  
pp. 100311
Author(s):  
Daniella C. Terenzi ◽  
Ehab Bakbak ◽  
Justin Z. Trac ◽  
Mohammad Al-Omran ◽  
Adrian Quan ◽  
...  
Keyword(s):  
Whole Blood ◽  
Progenitor Cell ◽  
Blood Samples ◽  
Human Whole Blood ◽  
Isolation And Characterization ◽  
Whole Blood Samples

The distribution of BrKα/RbKα peak intensity ratio in human whole blood samples

1994 ◽  
Vol 42 (3) ◽  
pp. 231-241 ◽  
Author(s):  
C. Shenberg ◽  
S. Spiegel ◽  
S. Chaitchik ◽  
P. Jordan ◽  
M. Kitzis ◽  
...  
Keyword(s):  
Whole Blood ◽  
Intensity Ratio ◽  
Peak Intensity Ratio ◽  
Blood Samples ◽  
Human Whole Blood ◽  
Peak Intensity ◽  
Whole Blood Samples

The effect of combined inhibition of C5aR1 and CD14 on phagocytosis of E. coli in human whole blood

Immunobiology ◽  
2016 ◽  
Vol 221 (10) ◽  
pp. 1220
Author(s):  
Dorte Christiansen ◽  
Espen Waage Skjeflo ◽  
Anne Landsem ◽  
Monica Dammen Mathisen ◽  
Hilde Fure ◽  
...  
Keyword(s):  
Whole Blood ◽  
Human Whole Blood ◽  
E Coli

scholarly journals AB0095 PRECLINICAL CHARACTERIZATION OF CJ-15314, A HIGHLY SELECTIVE JAK1 INHIBITOR, FOR THE TREATMENT OF AUTOIMMUNE DISEASES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1347.2-1347
Author(s):  
S. Y. Ki ◽  
H. Shin ◽  
Y. Lee ◽  
H. R. Bak ◽  
H. Yu ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Whole Blood ◽  
Inflammatory Diseases ◽  
Selective Inhibition ◽  
Janus Kinase ◽  
Dependent Manner ◽  
Human Whole Blood

Background:Janus kinases (JAK1, JAK2, JAK3, and TYK2) play critical roles in mediating various cytokine signaling, and has been developed as a target for autoimmune diseases such as RA. Tofacitinib, oral Pan-JAK inhibitor, demonstrated efficacy in RA patients, but its widespread use is limited by safety issues. Baricitinib, JAK1/2 inhibitor, is also known to interfere with the hematopoiesis system, such as anemia and thrombocytopenia associated with suppression of JAK2 signals. Therefore, it is necessary to develop a new potent compound that selectively inhibits JAK1 over JAK2, 3Objectives:To identify the pharmacological characteristic based on efficacy of CJ-15314 as potent and selective JAK1 inhibitor for treatment of autoimmune disease.Methods:In vitro, cell-based, kinase panel, Kd value and human whole blood assay were performed to determine the inhibition potency and selectivity for JAK subfamily kinases. In vivo therapeutic potential was evaluated by RA model including rat Adjuvant-Induced Arthritis (AIA) and collagen-induced arthritic (CIA). To confirm the possibility of further expansion into the autoimmune disease, BioMAP® Diversity PLUS® Panel was performed by discoverX.Results:In vitro assay, CJ-15314 inhibited JAK kinase family in a concentration-dependent manner with IC50 values of 3.8 nM against JAK1, Selectivity for JAK1 over JAK2, 3 was approximately 18, 83 fold greater for CJ-15314. In 1mM ATP condition, CJ-15314 has been confirmed to have the highest JAK1 selectivity over competing drugs, under 1 mM ATP condition that reflects the physiological environment in the body. Similarly, Kd values has also confirmed the selectivity of JAK1, which is 10 fold higher than JAK2, 3. Accordingly, in human whole blood assays, CJ-15314 is 11 fold more potent against IL-6 induced pSTAT1 inhibition through JAK1 (IC50 value: 70 nM) than GM-CSF-induced pSTAT5 inhibition (JAK2) whereas baricitinib and filgotinib exhibited only 2 fold and 7 fold respectively.In vivo efficacy model, CJ-15314 inhibited disease severity scores in a dose dependent manner. In the rat AIA model, CJ-15314 at 30 mg/kg dose showed 95.3% decrease in arthritis activity score, 51.2% in figotinib at 30 mg/kg, 97.7% showed baricitinib at 10 mg/kg. CJ-15314 showed superior anti-arthritic efficacy than filgotinib. CJ-15314 also minimally affected anemia-related parameters but not bricitinib end of the 2-week treatment. In the rat CIA model, like 10 mg/kg of bricitinib, 30 mg/kg of CJ-15314 also has a similar effect, with a significant reduction in histopathological scores.In biomap diversity panel, CJ-15314 inhibited the expression of genes such as MCP-1, VCAM-1, IP-10, IL-8, IL-1, sTNF-α and HLA-DR confirming the possibility of expansion into other diseases beyond arthritis.Conclusion:CJ-15314 is a highly selective JAK1 inhibitor, demonstrates robust efficacy in RA animal model and is good candidate for further development for inflammatory diseases.* CJ-15314 is currently conducting a phase I trial in south Korea.References:[1]Clark JD et al. Discovery and development of Janus kinase (JAK) inhibitors for inflammatory diseases. J Med Chem. 2014; 57(12):5023-38.[2]Burmester GR et al. Emerging cell and cytokine targets in rheumatoid arthritis. Nat Rev Rheumatol. 2014; 10(2):77-88[3]Jean-Baptiste Telliez et al. Discovery of a JAK3-selective inhibitor: functional differentiation of JAK3-selective inhibition over pan-JAK or JAK1-selective inhibition. ACS Chem. Biol., 2016; 11 (12):3442-3451Disclosure of Interests:so young Ki Employee of: CJ healthcare, hyunwoo shin Employee of: CJ healthcare, yelim lee Employee of: CJ healthcare, Hyoung rok Bak Employee of: CJ healthcare, hana yu Employee of: CJ healthcare, Seung Chan Kim Employee of: CJ healthcare, juhyun lee Employee of: CJ healthcare, donghyun kim Employee of: CJ healthcare, Dong-hyun Ko Employee of: CJ Healthcare, dongkyu kim Employee of: CJ healthcare

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