p38 MAP Kinase Inhibitor XX, FGA-19

A cell-permeable, benzoxadiazole compound designed to target p38 c-terminal "docking domain" that mediates interactions with upstream regulators and downstream substrates outside p38 active center. Selectively inhibits MEF-2A phosphorylation by activated p38α (IC₅₀ = 6.31 M; [p38] = 1 nM, [MEF-2a] = 10 nM, [ATP] = 25 M) with little or no potency against a panel of other kinases or the docking site interaction-independent MBP phosphorylation by p38. Shown to inhibit LPS-stimulated phosphorylation of p38, MK2, and Hsp27 in THP-1 cells (1 to 5 M; 1 h drug preincubation), while reduced inhibition against JNK1 & Erk1/2 is only observed at a high concentration of 5 M. Although SB203580 (Cat. Nos. 559389, 559395, and 559398) exhibits similar potency as FGA-19 in inhibiting LPS-induced TNFα secretion in THP-1 cultures in vitro, only FGA-19 (1 g/5 L/mouse), but not SB203580 (up to 5 g/mouse), intrathecal injection results in lasting (>5 days) reduction of heat sensitivity of paws received carrageenan injection among either wild-type or LysM-GRK2^+/- mice in vivo.

A cell-permeble, benzoxadiazole compound designed to target p38 c-terminal "docking domain" that mediates interactions with upstream regulators and downstream substrates outside p38 active center. Selectively inhibits MEF-2A phosphorylation by activated p38α (IC₅₀ = 6.31 M; [p38] = 1 nM, [MEF-2a] = 10 nM, [ATP] = 25 M) with little or no potency against a panel of other kinases or the docking site interaction-independent MBP phosphorylation by p38. Shown to inhibit LPS-stimulated phosphorylation of p38, MK2, and Hsp27 in THP-1 cells (1 to 5 M; 1 h drug preincubation prior to 30 to 60 min LPS exposure), while reduced inhibition against JNK1 & Erk1/2 is only observed at a high concentration of 5 M, indicating weaker potency in targeting JNK & Erk docking domain. Although SB203580 (Cat. Nos. 559389, 559395, and 559398) exhibits similar potency as FGA-19 in inhibiting LPS-induced TNFα secretion in THP-1 cultures in vitro, only FGA-19 (1 g/5 L/mouse), but not SB203580 (up to 5 g/mouse), intrathecal injection results in lasting (>5 days) reduction of heat sensitivity of paws received carrageenan injection among either wild-type (6 d prior to drug treatment; 20 L 2% carrageenan per paw) or LysM-GRK2^+/- mice (5 L 1% carrageenan per paw) in vivo.

Cell permeable: yes

Primary Target
p38 MAPK

Reversible: yes

Target IC₅₀: 6.31 µM for p38 MAPK-mediated phosphorylation of MEF-2A-Thr312

Packaged under inert gas

Use only fresh DMSO for reconstitution.

Willemen, H. L., et al. 2014. Biochem. J.459, 427.

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Toxicity: Standard Handling (A)