General description

A cell-permeable benzoylthiourea compound that acts as a reversible inhibitor of class III HDAC sirtuins (IC₅₀ against SirT2 ~10 µM). Based on studies using the more soluble analog Tenovin-6, Tenovin-1 is expected not to compete with substrate binding and display lower potency against SirT1/3 (IC₅₀ = 21/67 µM using Tenovin-6). Tenovin-1 (10 µM) up-regulates cellular p53 protein, but not mRNA, level in MCF-7 (≥6-fold in 6 h), presumably by blocking mdm2-mediated p53 degradation. Two day Tenovin-1 treatment (10 µM) results in selective killing of cancer cells with functional p53, but not p53-lacking cancer cells or normal human dermal fibroblasts. Despite its low aqueous solubility, administration of Tenovin-1 suspension is shown to effectively reduce BL2 and ARN8 xenographs in mice in vivo (≥50% reduction with 92 mg/kg daily i.p.).

A cell-permeable benzoylthiourea compound that acts as a reversible inhibitor of class III HDAC sirtuins against SirT2 (IC₅₀ = ~ 10 µM). Based on studies using the more soluble analog Tenovin-6, Tenovin-1 is expected not to compete with substrate binding and display lower potency against SirT1/3 (IC₅₀ = 21/67 µM using Tenovin-6). Tenovin-1 (10 µM) up-regulates cellular p53 protein, but not mRNA, level in MCF-7 (≥6-fold in 6 h), presumably by blocking mdm2-mediated p53 degradation. Two day Tenovin-1 treatment (10 µM) results in selective killing of cancer cells with functional p53, but not p53-lacking cancer cells or normal human dermal fibroblasts. Despite its low aqueous solubility, administration of Tenovin-1 suspension is shown to effectively reduce BL2 and ARN8 xenographs in mice in vivo (≥50% reduction with 92 mg/kg, daily, i.p.).

Legal Information

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

Other Notes

Lain, S., et al. 2008. Cancer Cell13, 454.

Packaging

Packaged under inert gas

10 mg in Plastic ampoule

Reconstitution

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

Warning

Toxicity: Standard Handling (A)