5.31661

SMYD2 Inhibitor, AZ505

• Synonyme(s) : SMYD2 Inhibitor, AZ505, N-Cyclohexyl-3-(3,4-dichlorophenethylamino)-N-(2-(2-(5-hydroxy-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)ethylamino)ethyl)propanamide, HMTase Inhibitor XV
• Formule empirique (notation de Hill): C₂₉H₃₈Cl₂N₄O₄
• Numéro CAS: 1035227-43-0
• Poids moléculaire : 577.54
• Code UNSPSC : 12352200

Propriétés

• Essai: ≥95% (HPLC)
• Niveau de qualité: 100
• Forme: solid
• Fabricant/nom de marque: Calbiochem^®
• Conditions de stockage: OK to freeze; protect from light
• Couleur: off-white
• Solubilité: DMSO: 50 mg/mL
• Température de stockage: 2-8°C
• InChI: 1S/C29H38Cl2N4O4/c30-23-8-6-20(18-24(23)31)10-13-32-15-12-27(38)35(22-4-2-1-3-5-22)17-16-33-14-11-21-7-9-25(36)28-29(21)39-19-26(37)34-28/h6-9,18,22,32-33,36H,1-5,10-17,19H2,(H,34,37)
• Clé InChI: LIBVHXXKHSODII-UHFFFAOYSA-N

Description

Description générale

A cell-permeable benzooxazinyl-ethylaminoethyl-propanamide compound that acts as a potent and reversible inhibitor of SMYD2 (IC₅₀ = 120 nM, K_i = 300 nM, K_d = 500 nM). Shown to bind to the peptide-binding groove of the enzyme. This binding is dependent on the presence of S-adenosylmethionine (SAM). The inhibition appears to be competitive with respect to substrate and uncompetitive with respect to SAM. Displays ~700-fold greater selectivity over SMYD3, DOT1L, EZH2, GLP, G9a and SET7/9 protein lysine methyl transferases (IC₅₀ >83.3 µM). Inhibits SMYD2-mediated p53-K370 methylation in U2OS cells (at ~10 µM), but does not affect methylation in cells transfected with a Y240F mutant.

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

A cell-permeable benzooxazinyl-ethylaminoethyl-propanamide compound that inhibits SMYD2-mediated p53 peptide (aa 361-380) K370me monomethylation (IC₅₀ = 120 nM; [SAM] = [p53 peptide] = 1 µM; pH 7.4 for 90 min) in a substrate-competitive, but cofactor S-adenosylmethionine-(AdoMet/SAM) uncompetitive manner (K_i = 0.3 µM) by targeting SAM-bound SMYD2 at the substrate-binding site (K_d = 0.5 µM) via simultaneous interactions with SAM donor methyl group as well as residues from the core SET, I-SET, and post-SET domains, while exhibiting little potency toward DOT1L, EZH2, G9A, GLP, SET7/9, or SMYD3 (IC₅₀ >83.3 µM). Shown to effectively abolish cellular p53 K370me in U2OS wt SMYD2 transfectants to the same level seen in U2OS transfected with inactive SMYD2 Y240F mutant (10 µM for 24 h).

AZ505 is a cell-permeable, potent, reversible inhibitor of SMYD2 (IC₅₀ = 120 nM, K_i = 300 nM) that binds to the peptide-binding groove of the enzyme.

Actions biochimiques/physiologiques

Cell permeable: yes

Primary Target
SMYD2

Avertissement

Toxicity: Standard Handling (A)

Forme physique

Supplied as a di-trifluoroacetate salt.

Reconstitution

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

Use only fresh DMSO for reconstitution.

Autres remarques

Ferguson, A.D., et al. 2011. Structure19, 1262.

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