2 research outputs found
The Identification and Pharmacological Characterization of 6‑(<i>tert</i>-Butylsulfonyl)‑<i>N</i>‑(5-fluoro‑1<i>H</i>‑indazol-3-yl)quinolin-4-amine (GSK583), a Highly Potent and Selective Inhibitor of RIP2 Kinase
No full textRIP2 kinase is a central component
of the innate immune system
and enables downstream signaling following activation of the pattern
recognition receptors NOD1 and NOD2, leading to the production of
inflammatory cytokines. Recently, several inhibitors of RIP2 kinase
have been disclosed that have contributed to the fundamental understanding
of the role of RIP2 in this pathway. However, because they lack either
broad kinase selectivity or strong affinity for RIP2, these tools
have only limited utility to assess the role of RIP2 in complex environments.
We present, herein, the discovery and pharmacological characterization
of GSK583, a next-generation RIP2 inhibitor possessing exquisite selectivity
and potency. Having demonstrated the pharmacological precision of
this tool compound, we report its use in elucidating the role of RIP2
kinase in a variety of in vitro, in vivo, and ex vivo experiments,
further clarifying our understanding of the role of RIP2 in NOD1 and
NOD2 mediated disease pathogenesis
The Identification and Pharmacological Characterization of 6‑(<i>tert</i>-Butylsulfonyl)‑<i>N</i>‑(5-fluoro‑1<i>H</i>‑indazol-3-yl)quinolin-4-amine (GSK583), a Highly Potent and Selective Inhibitor of RIP2 Kinase
No full textRIP2 kinase is a central component
of the innate immune system
and enables downstream signaling following activation of the pattern
recognition receptors NOD1 and NOD2, leading to the production of
inflammatory cytokines. Recently, several inhibitors of RIP2 kinase
have been disclosed that have contributed to the fundamental understanding
of the role of RIP2 in this pathway. However, because they lack either
broad kinase selectivity or strong affinity for RIP2, these tools
have only limited utility to assess the role of RIP2 in complex environments.
We present, herein, the discovery and pharmacological characterization
of GSK583, a next-generation RIP2 inhibitor possessing exquisite selectivity
and potency. Having demonstrated the pharmacological precision of
this tool compound, we report its use in elucidating the role of RIP2
kinase in a variety of in vitro, in vivo, and ex vivo experiments,
further clarifying our understanding of the role of RIP2 in NOD1 and
NOD2 mediated disease pathogenesis
