Erbstatin

Erbstatin is an inhibitor of EGF receptor-associated tyrosine kinase that has been found in Streptomyces.^1,2 It is selective for EGF receptor-associated tyrosine kinase over protein kinase A (PKA) and PKC, but does inhibit phosphatidylinositol kinase (IC₅₀s = 0.2, 100, >179, and 25 µg/ml, respectively).¹ Erbstatin (10 µg/ml) induces apoptosis and DNA fragmentation in L1210 murine skin lymphocytic leukemia cells.² It inhibits LPS-induced production of prostaglandin F_2α and nitrite in J774.2 macrophages in a concentration-dependent manner.³ Erbstatin (4 mg/animal) reduces tumor growth in an MCF-7 breast cancer mouse xenograft model when used in combination with the iron chelator foroxymithine, which prevents its degradation.⁴

1.Onoda, T., Iinuma, H., Sasaki, Y., et al.Isolation of a novel tyrosine kinase inhibitor, lavendustin A, from Streptomyces griseolavendusJ. Nat. Prod.52(6)1252-1257(1989) 2.Simizu, S., Imoto, M., and Umezawa, K.Induction of apoptosis by erbstatin in mouse leukemia L1210 cellsBiosci. Biotech. Biochem.58(9)1549-1552(1994) 3.Akarasereenont, P., Mitchell, J.A., Appleton, I., et al.Involvement of tyrosine kinase in the induction of cyclo-oxygenase and nitric oxide synthase by endotoxin in cultured cellsBr. J. Pharmacol.113(4)1522-1528(1994) 4.Toi, M., Mukaida, H., Wada, T., et al.Antineoplastic effect of erbstatin on human mammary and esophageal tumors in athymic nude miceEur. J. Cancer26(6)722-724(1990)