5.00655

Rad6 Inhibitor, TZ9

• Synonym(s): Rad6 Inhibitor, TZ9, TZ9, TZ-9, TZ 9, HHR6 Inhibitor, 4-Amino-6-(phenylamino)-[1,3,5]triazin-2-yl)methyl-4-nitrobenzoate, (4-Amino-6-(phenylamino)-1,3,5-triazin-2-yl)methyl 4-nitrobenzoate
• Empirical Formula (Hill Notation): C₁₇H₁₄N₆O₄
• CAS Number: 1002789-86-7
• Molecular Weight: 366.33
• UNSPSC Code: 12352200
• PubChem Substance ID: 7593228
• NACRES: NA.77

Properties

• Assay: ≥99% (HPLC)
• Quality Level: 200
• form: solid
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze
• color: pale yellow
• solubility: DMSO: 100 mg/mL
• storage temp.: 2-8°C
• SMILES string: C1=CC=C(C=C1)NC2=NC(=NC(=N2)N)COC(=O)C3=CC=C(C=C3)[N+](=O)[O-]

Description

General description

A cell-permeable triazine compound that directly targets human E2 Ubiquitin-conjugating enzyme Rad6B/HHR6B catalytic site via noncovalent interactions and effectively inhibits Rad6B-Ub thioester bond formation as well as subsequent substrate ubiquitination without affecting UbcH5B/UBE2D2-catalyzed BCA2 ubiquitination. Shown to inhibit the proliferation of high Rad6B-expressing MDA-MB-231 (IC₅₀ = 6 µM in 72 h), but not the low Rad6B-expressing, non-transformed MCF10A, via G2/M arrest and apoptosis induction. Two known cellular Rad6 substrates, β-catenin and PCNA, are reported to be downregulated following 24 h inhibitor treatment in MDA-MB-231 cultures (0.5 to 5 µM).

A cell-permeable triazine compound that is reported to directly target human E2 Ubiquitin-conjugating enzyme Rad6B/HHR6B catalytic site via noncovalent interactions and effectively inhibit Rad6B-Ub thioester bond formation and subsequent Ub transfer to H2A (by 61%; 1 h 25 nM drug preincubation prior to 1 h H2A ubiquitination reactoin) without affecting UbcH5B/UBE2D2-catalyzed BCA2 ubiquitination. Shown to inhibit the proliferation of high Rad6B-expressing MDA-MB-231 (IC₅₀ = 6 µM in 72 h by MTT assays; 96.3% inhibition of 24 h colony formation by 10 µM inhibitior) via G2/M arrest and apoptosis induction, while exhibiting little toxicity toward low Rad6B-expressing, non-transformed MCF10A (2% and 19% inhibition in 72 h by 10 and 50 µM inhibitor, respectively; by MTT assays). Two known cellular Rad6 substrates, β-catenin and PCNA, are shown to be downregulated following 24 h inhibitor treatment in a dose-dependent manner in MDA-MB-231 cultures (0.5 to 5 µM).

Biochem/physiol Actions

Cell permeable: yes

Primary Target
Rad6B/HHR6B

Reversible: yes

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

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.

Other Notes

Sanders, M.A., et al. 2013. Mol. Cancer Ther.12, 373.

Legal Information

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

Safety Information

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 2
• Flash Point(F): Not applicable
• Flash Point(C): Not applicable