Cdc34 Inhibitor, CC0651-CAS 1319207-44-7-Calbiochem

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一般描述

A cell-permeable biphenylylpentanoic acid compound that acts as a selective allosteric inhibitor of E2 ubiquitin-conjugating enzyme Cdc34 (IC₅₀= 2.5 ?M in a Sic1-SCF^Cdc4assay) without affecting the activities of E1 or E3 ligases. Reported to act by trapping a weak interaction between ubiquitin and the E2 donor ubiquitin-binding site and may serve as a molecular bridge between Cdc34A and ubiquitin. Binds to Cdc34ACAT alone with an EC₅₀value of 267 ?M, but in the presence of ubiquitin, this affinity is significantly increased (EC₅₀= 19 ?M). Does not disrupt the interaction of Cdc34A with the RING domain of Rbx1 and is suggested to even moderately stabilize this interaction. Shown to inhibit p27^Kip1ubiquitination (IC₅₀= 1.72 ?M) and reduce PC-3 cancer cells proliferation (~30 ?M).

Please note that the molecular weight for this compound is batch-specific due to variable water content.
A cell-permeable and aqueous soluble (~ 1 mg/mL or 2.26 mM at pH 7.4) biphenylylpentanoic acid that selectively inhibits human, but not yeast, E2 Ub-conjugating enzyme Cdc34- dependent substrates ubiquitinations in p27^kip1-SCF^Skp2, Sic1-SCF^Cdc4(IC₅₀= 1.72 & 2.5 ?M, respectively), Cyclin E-SCF^Fbw7, IκBα-SCF^βTrCPubiquitination assays and induces cellular p27^kip1and cyclin E accumulation (30 ?M for 16 h in PC-3 cultures), displaying no affinity or inhibitory activity against other E1 (Uba1), E2 (Cdc34B/Ube2R2,Ube2G1, UbeU1), HECT E3 (SMURF 2, UbcH7), or RING E3 (Rnf168) tested. CC0651 is shown to target Ub-bound Cdc34 with a 14-fold higher affinity than the non-Ub-bound Cdc34 via an allosteric binding pocket at the periphery of the Cdc34-Ub interface. In addition to inhibit the reactivity of the Cdc34-Ub complex via direct binding, the CC0651-bound Cdc34-Ub complex itself is reported to exhibit higher affinity toward SCF E3 complex and thereby exhibit a dominant negative effect by effectively competing against functional Cdc34-Ub complex for SCF binding.

生化/生理作用

Cell permeable: yes
Primary Target
E2 ubiquitin-conjugating enzyme Cdc34
Reversible: yes

包装

Packaged under inert gas

警告

Toxicity: Standard Handling (A)

重悬

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

其他说明

Huang, H., et al. 2013.Nat. Chem. Biol.10,156.

Ceccarelli, D.F., et al. 2011.Cell145,1075.

法律信息

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

基本信息

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