Leon Chang
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View article: The mode of action of IL-23 in experimental inflammatory arthritic pain and disease
The mode of action of IL-23 in experimental inflammatory arthritic pain and disease Open
Objectives We have previously reported using gene-deficient mice that the interleukin (IL)-23p19 subunit is required for the development of innate immune-driven arthritic pain and disease. We aimed to explore here, using a number of in viv…
View article: JNJ-77242113, a highly potent, selective peptide targeting the IL-23 receptor, provides robust IL-23 pathway inhibition upon oral dosing in rats and humans
JNJ-77242113, a highly potent, selective peptide targeting the IL-23 receptor, provides robust IL-23 pathway inhibition upon oral dosing in rats and humans Open
The interleukin (IL)-23 pathway is a pathogenic driver in psoriasis, psoriatic arthritis, and inflammatory bowel disease. Currently, no oral therapeutics selectively target this pathway. JNJ-77242113 is a peptide targeting the IL-23 recept…
View article: IL-23 regulation of myeloid cell biology during inflammation
IL-23 regulation of myeloid cell biology during inflammation Open
Interleukin (IL)-23 is implicated in the pathogenesis of several inflammatory diseases and is usually linked with helper T cell (Th17) biology. However, there is some data linking IL-23 with innate immune biology in such diseases. We there…
View article: P626 JNJ-77242113, an oral peptide selectively targeting the IL-23 receptor, demonstrates pharmacodynamic activity in rat and human colon tissue explants following oral dosing
P626 JNJ-77242113, an oral peptide selectively targeting the IL-23 receptor, demonstrates pharmacodynamic activity in rat and human colon tissue explants following oral dosing Open
Background The interleukin (IL)-23 pathway is a pathogenic driver in psoriasis, psoriatic arthritis, and inflammatory bowel disease (IBD). There are currently no approved oral therapies selectively targeting the IL-23 pathway. JNJ-77242113…
View article: Identification of highly selective SIK1/2 inhibitors that modulate innate immune activation and suppress intestinal inflammation
Identification of highly selective SIK1/2 inhibitors that modulate innate immune activation and suppress intestinal inflammation Open
The salt-inducible kinases (SIK) 1–3 are key regulators of pro- versus anti-inflammatory cytokine responses during innate immune activation. The lack of highly SIK-family or SIK isoform-selective inhibitors suitable for repeat, oral dosing…
View article: Discovery of JNJ-64264681: A Potent and Selective Covalent Inhibitor of Bruton’s Tyrosine Kinase
Discovery of JNJ-64264681: A Potent and Selective Covalent Inhibitor of Bruton’s Tyrosine Kinase Open
Bruton's tyrosine kinase (BTK) is a Tec family kinase that plays an essential role in B-cell receptor (BCR) signaling as well as Fcγ receptor signaling in leukocytes. Pharmacological inhibition of BTK has been shown to be effective in trea…
View article: Discovery of a Potent and Selective Covalent Inhibitor of Bruton’s Tyrosine Kinase with Oral Anti-Inflammatory Activity
Discovery of a Potent and Selective Covalent Inhibitor of Bruton’s Tyrosine Kinase with Oral Anti-Inflammatory Activity Open
Bruton's tyrosine kinase (BTK) is a cytoplasmic tyrosine kinase that plays a critical role in the activation of B cells, macrophages, and osteoclasts. Given the key role of these cell types in the pathology of autoimmune disorders, BTK inh…
View article: EVOLUTIONARY MATHEMATICS AND SCIENCE FOR GENERAL FAMOUS NUMBERS: STIRLING-EULER-LAH-BELL
EVOLUTIONARY MATHEMATICS AND SCIENCE FOR GENERAL FAMOUS NUMBERS: STIRLING-EULER-LAH-BELL Open
We first introduce Pascal, Stirling, Eulerian, Lah and Bell numbers via sorting, then generalize Stirling numbers of both kinds [■(n@k)], {■(n@k)}, Eulerian numbers of two orders 〈■(n@k)〉, 〈〈■(n@k)〉 〉, Lah numbers L(n,k)=∑_(j=1)^n▒[■(n@j)]…
View article: A Single Amino Acid Difference between Mouse and Human 5-Lipoxygenase Activating Protein (FLAP) Explains the Speciation and Differential Pharmacology of Novel FLAP Inhibitors
A Single Amino Acid Difference between Mouse and Human 5-Lipoxygenase Activating Protein (FLAP) Explains the Speciation and Differential Pharmacology of Novel FLAP Inhibitors Open
5-Lipoxygenase activating protein (FLAP) plays a critical role in the metabolism of arachidonic acid to leukotriene A4, the precursor to the potent pro-inflammatory mediators leukotriene B4 and leukotriene C4 Studies with small molecule in…
View article: Preclinical Characterization of the FAAH Inhibitor JNJ-42165279
Preclinical Characterization of the FAAH Inhibitor JNJ-42165279 Open
The pre-clinical characterization of the aryl piperazinyl urea inhibitor of fatty acid amide hydrolase (FAAH) JNJ-42165279 is described. JNJ-42165279 covalently inactivates the FAAH enzyme, but is highly selective with regard to other enzy…