(-)-Terreic Acid, Synthetic

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.

Cell permeable: yes

Primary Target
Bruton′s tyrosine kinase catalytic activity (BTK)

Product competes with ATP.

Reversible: yes

Target IC₅₀: 10 µM against BTK

Packaged under inert gas

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

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.

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

Toxicity: Harmful (C)