A. Wako's Unique Products - 1. Inhibitors
Wako commercialized new inhibitors which were discovered by Dr. Hiroyuki Osada, Antibiotics laboratory of Institute of Physical and Chemical Research (RIKEN) under license from RIKEN.
c. HSP60 Inhibitor
Wako Catalog No. 051-07671 (200 μL) <for Cellbiology> Keep at -20°C
This product is a derivative of epolactaene isolated from Penicillium. It has a more potent cytostatic effect on human neuroblastoma cells SH-SY 5Y than that of epolactaene, and induces apoptosis. Furthermore, it has been revealed that ETB induces apoptosis in human T-lymphoma cells Jurkat. Recently, HSP60 was identiﬁed as one of ETB binding proteins. ETB binds to HSP60 to inhibit chaperone activity.
Nagumo, Y., Kakeya, H., Shoji, M., Hayashi, Y., Dohmae, N. and Osada, H., “Epolactaene binds human Hsp60 Cys442 resulting in the inhibition of chaperone activity” : Biochem. J., 387(3), 835-40 (2005)
d. Protein Synthesis Inhibitor
Wako Catalog No. 185-02181 (500 μg) <for Cellbiology> Keep at -20°C
This product is an antibiotic isolated from Streptomyces. It targets isoleucyl-tRNA synthetase and inhibits protein synthesis in eukaryotes. It has been investigated for its antitumor and antifungal activities. However, recent studies have revealed that low-dose of reveromycin A induces cell death of activated osteoclasts, which leads to acidic environment. Thus it receives attention as a candidate for the treatment of osteoporosis/ multiple myeloma. (This product is a sodium salt of the compound shown below.)
Woo, J.T., Kawatani, M., Kato, M., Shinki, T., Yonezawa, T., Kanoh, N., Nakagawa, H., Takami, M., Lee, K.H., Stern, P.H., Nagai, K. and Osada, H., “Reveromycin A, an agent for osteoporosis, inhibits bone resorption by inducing apoptosis speciﬁ cally in osteoclasts” : Proc. Natl. Acad. Sci. USA, 103 (12), 4729-34(2006).
e. Apoptosis Inhibitor
Wako Catalog No. 182-02191 (200 μg) <for Cellbiology> Keep at -20°C
This product is a derivative of epoxycylohexenone isolated from Paecilomyces. It has lower toxicity than epoxycylohexenone. Like epoxycylohexenone, it inhibits apoptosis not by inhibition of perforin-dependent pathway by cytotoxic T lymphocytes but by selective inhibition of Fas ligand-dependent pathway alone.
Mitsui, T., Miyake, Y., Kakeya, H., Hayashi, Y., Osada, H. & Kataoka, T., “RKTS-33, an epoxycyclohexenone derivative that speciﬁ cally inhibits Fas ligand-dependent apoptosis in CTL-mediated cytotoxicity” : Biosci. Biotechnol. Biochem., 69 (10), 1923-8 (2005).
f. Cell Cycle Inhibitor
Wako Catalog No. 203-16961 (500 μg) <for Cellbiology> Keep at -20°C
This product is an alkaloid antibiotic isolated from Aspergillus fumigatus. It affects the microtubule-associated protein binding site and exhibits antitumor activity by inhibition of cell cycle progression in the M phase speciﬁcally.