Tenovin-1 - CAS 380315-80-0 - Calbiochem

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.).

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.

Other Notes

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

Legal Information

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