Biochem/physiol Actions

Primary TargetBruton′s tyrosine kinase catalytic activity (BTK)

Reversible: yes

Product competes with ATP.

Target IC₅₀: 10 µM against BTK

Cell permeable: yes

General description

A cell-permeable quinone epoxide antibiotic that acts as a reversible, substrate competitive, and selective inhibitor of Bruton′s tyrosine kinase (BTK; IC₅₀ = 10 µM and 3 µM for the basal and activation levels), both in vitro and in vivo. Shown to bind to the BTK pleckstrin homology domain (BTK-PH) and block the interaction between BTK-PH and protein kinase C (PKC) (IC₅₀ ~100 µM in human mast cell lysates), thus affecting the catalytic activity of BTK, but not the activity of PKC. Selectively inhibits the autophosphorylation of PKC_βI (IC₅₀ ~8 µM) but not that of PKC_βII. Reported to effectively inhibit the production of TNF-α (IC₅₀ ~3 µM) and block the activation of JNK1 (IC₅₀ ~10 µM) in FcεRI-stimulated mast cells. Also reported to inhibit DNA synthesis in activated spleen cells (IC₅₀ ~1.5 µM). Does not significantly affect the activities of Lyn, Syk, PKA, CK-1, ERK1, ERK2 and p38 kinases.

A cell-permeable quinone epoxide antibiotic that acts as a reversible, substrate competitive, and selective inhibitor of Bruton's tyrosine kinase catalytic activity (BTK; IC₅₀ = 10 µM and 3 µM for the basal and activation levels). Shown to bind to the BTK pleckstrin homology domain (BTK-PH) and block the interaction between the BTK-PH and PKC (IC₅₀ = ~ 100 µM in human mast cell lysates), thus affecting the catalytic activity of BTK, but not of PKC. Selectively inhibits the autophosphorylating activity of PKC_βI (IC₅₀ = ~ 8 µM) and not of PKC_βII. Reported to effectively inhibit the production of TNF-α (IC₅₀ = ~ 3 µM), and activation of JNK1 (IC₅₀ = ~ 10 µM) in FcεRI-stimulated mast cells. Also inhibits the DNA synthesis in activated spleen cells (IC₅₀ = ~ 1.5 µM). Does not significantly affect the activities of Lyn, Syk, PKA, CK-1, ERK1, ERK2, and p38 kinases.

Legal Information

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

Other Notes

Kawakami, Y., et al. 2000. Proc. Natl. Acad. Sci. USA97, 7423.Kawakami, Y., et al. 1999. Proc. Natl. Acad. Sci. USA96, 2227.Yamamoto, H., et al. 1980. Jpn. J. Antibiot.33, 320.

Packaging

Packaged under inert gas

2 mg in Glass bottle

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Warning

Toxicity: Harmful (C)