5.09704

Cdc34 Inhibitor, CC0651

• Synonyme(s) : Cdc34 Inhibitor, CC0651, 4,5-Dideoxy-5-(3ʹ,5ʹ-dichloro-4-biphenylyl)-4-((methoxyacetyl)amino)-L-arabinonic acid, (2 R,3 S,4 S)-5-(3ʹ,5ʹ-Dichloro-(1,1ʹ-biphenyl)-4-yl)-2,3-dihydroxy-4-(2 methoxyacetamido)pentanoic acid, Cdc34A Inhibit
• Formule empirique (notation de Hill): C₂₀H₂₁Cl₂NO₆
• Numéro CAS: 1319207-44-7
• Poids moléculaire : 442.29
• Code UNSPSC : 12352200
• Nomenclature NACRES : NA.77

Propriétés

• Pureté: ≥98% (HPLC)
• Niveau de qualité: 100
• Forme: powder
• Pureté optique: ee: ≥98%
• Fabricant/nom de marque: Calbiochem^®
• Conditions de stockage: OK to freeze; protect from light
• Couleur: off-white
• Solubilité: DMSO: 100 mg/mL
• Température de stockage: −20°C
• InChI: 1S/C20H21Cl2NO6/c1-29-10-17(24)23-16(18(25)19(26)20(27)28)6-11-2-4-12(5-3-11)13-7-14(21)9-15(22)8-13/h2-5,7-9,16,18-19,25-26H,6,10H2,1H3,(H,23,24)(H,27,28)/t16-,18-,19+/m0/s1
• Clé InChI: NTCBTNCWNRCBGX-YTQUADARSA-N

Description

Description générale

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 µM, respectively), Cyclin E-SCF^Fbw7, IκBα-SCF^βTrCP ubiquitination assays and induces cellular p27^kip1 and cyclin E accumulation (30 µM 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.

A cell-permeable biphenylylpentanoic acid compound that acts as a selective allosteric inhibitor of E2 ubiquitin-conjugating enzyme Cdc34 (IC₅₀ = 2.5 µM in a Sic1-SCF^Cdc4 assay) 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 EC₅₀ value of 267 µM, but in the presence of ubiquitin, this affinity is significantly increased (EC₅₀ = 19 µM). 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^Kip1 ubiquitination (IC₅₀ = 1.72 µM) and reduce PC-3 cancer cells proliferation (~30 µM).

Please note that the molecular weight for this compound is batch-specific due to variable water content.

Actions biochimiques/physiologiques

Cell permeable: yes

Primary Target
E2 ubiquitin-conjugating enzyme Cdc34

Reversible: yes

Conditionnement

Packaged under inert gas

Avertissement

Toxicity: Standard Handling (A)

Reconstitution

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

Autres remarques

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

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

Informations légales

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

Informations sur la sécurité

• Code de la classe de stockage: 11 - Combustible Solids
• Classe de danger pour l'eau (WGK): WGK 3
• Point d'éclair (°F): Not applicable
• Point d'éclair (°C): Not applicable