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Discovery of VX-509 (Decernotinib): A Potent and Selective Janus Kinase 3 Inhibitor for the Treatment of Autoimmune Diseases.
TLDR
It appears that VX-509 (decernotinib), a novel, potent, and selective JAK3 inhibitor, which demonstrates good efficacy in vivo in the rat host versus graft model (HvG), appears to offer potential for the treatment of a variety of autoimmune diseases.
VX-509 (Decernotinib) Is a Potent and Selective Janus Kinase 3 Inhibitor That Attenuates Inflammation in Animal Models of Autoimmune Disease
TLDR
It is demonstrated that VX-509 is a selective and potent inhibitor of JAK3 in vitro and modulates proinflammatory response in models of immune-mediated diseases, such as collagen-induced arthritis and delayed-type hypersensitivity.
2-Aminopyrazolo[1,5-a]pyrimidines as potent and selective inhibitors of JAK2.
TLDR
The discovery and structure based optimization of a novel series of 2-amino-pyrazolo[1,5-a]pyrimidines that exhibit potent inhibition of JAK2 are described.
A Randomized, Double‐Blind, Placebo‐Controlled, Twelve‐Week, Dose‐Ranging Study of Decernotinib, an Oral Selective JAK‐3 Inhibitor, as Monotherapy in Patients With Active Rheumatoid Arthritis
TLDR
To assess the efficacy and safety of oral decernotinib monotherapy in a 12‐week, randomized, double‐blind, placebo‐controlled, dose‐ranging study of patients with rheumatoid arthritis (RA).
Janus kinase 2 inhibitors. Synthesis and characterization of a novel polycyclic azaindole.
The synthesis and characterization of a novel polycyclic azaindole based derivative is disclosed, and its binding to JAK2 is described. The compound is further evaluated for its ability to block the
Discovery and SAR of novel 4-thiazolyl-2-phenylaminopyrimidines as potent inhibitors of spleen tyrosine kinase (SYK).
TLDR
A series of SYK inhibitors based on the phenylamino pyrimidine thiazole lead 4 provided compounds with nanomolar K(i)'s against SYK and potent inhibition in mast cell degranulation assays.
THU0160 The Effect of VX-509, a Selective Oral Jak3 Inhibitor, on Plasma Biomarkers of Disease Activity in Patients with Rheumatoid Arthritis
TLDR
VX-509 treatment modulated biomarkers of RA associated with inflammation with decreases from baseline in levels of IL-6, CD25, CCL18, and MMP-3 at week 12 that were dose-related, consistent with the efficacy of VX-508 in improving RA signs and symptoms.
Evaluation of Drug-Drug Interactions between VX-765 and Common Anti-Epileptic Medications in Subjects with Treatment-Resistant Partial-Onset Epilepsy (P02.216)
TLDR
VX-765 has minimal potential for drug-drug interactions with commonly administered anti-epileptic drugs (AEDs) and bioequivalence tests showed no significant changes in AED concentrations before and after co-administration with VX-763.
THU0141 Biomarker assessment of VX-509, an investigational selective JAK3 inhibitor, in healthy volunteers
TLDR
The PK/PD correlations of the experimental biomarkers demonstrated that VX-509 is a selective, reversible inhibitor of JAK3 signaling in humans, and warrants further clinical investigation in patients with chronic, immune-mediated inflammatory disorders, including rheumatoid arthritis.
Abstract LB-B15: A novel PI3K gamma isoform selective small molecule kinase inhibitor demonstrates single agent anti-tumor activity and enhanced combination activity with checkpoint blockade in
Immune checkpoint inhibitors have generated impressive clinical responses, however, a number of patients and cancer types remain resistant to checkpoint blockade. Immunosuppressive cells such as