TAME

Research use only, not for human use.

A small molecule anaphase-promoting complex/cyclosome (APC/C) inhibitor that binds to the APC preferentially suppresses APC/C(Cdc20) rather than APC/C(Cdh1).

A small molecule anaphase-promoting complex/cyclosome (APC/C) inhibitor that binds to the APC preferentially suppresses APC/C(Cdc20) rather than APC/C(Cdh1); inhibits cyclin proteolysis in mitotic Xenopus egg extract with IC50 of 12 uM; promotes Cdc20 autoubiquitination, blocks cyclin degradation in interphase extract.

The absence of APC substrates, TAME ejects Cdc20 from the APC by promoting Cdc20 auto-ubiquitination in its N-terminal region. Cyclin B1 antagonizes TAME's effect by promoting binding of free Cdc20 to the APC and suppressing Cdc20 auto-ubiquitination. TAME stabilizes cyclin B1 in Xenopus extract by two mechanisms. First, it reduces the kcat of the APCCdc20/cyclin B1 complex without affecting the Km, slowing the initial ubiquitination of unmodified cyclin B1. Second, as cyclin B1 becomes ubiquitinated, it loses its ability to promote Cdc20 binding to the APC in the presence of TAME. As a result, cyclin B1 ubiquitination terminates before reaching the threshold necessary for proteolysis.

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Tosyl-L-arginine methyl ester

Proteasome/Ubiquitin

E3 Ubiquitin Ligase

APC

Cancer

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901-47-3

342.4139

C14H22N4O4S

>98% (HPLC)

10 mM in DMSO

CC1=CC=C(C=C1)S(=O)(=O)NC(CCCN=C(N)N)C(=O)OC

L-Arginine, N2-[(4-methylphenyl)sulfonyl]-, methyl ester

(-20℃)

With Ice Pack

≥ 2 years