"目录号: HY-14531
Talarozole 是一种有效的CYP26A1和CYP26B1抑制剂，IC50分别为 5.1 nM 和 0.46 nM。
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生物活性
Description
Talarozole is a potent inhibitor of bothCYP26A1andCYP26B1, withIC50of 0.46 nM and 5.1 nM forCYP26B1andCYP26A1, respectively.
IC50& Target
IC50: 0.46/5.1 nM (CYP26B1/A1)[1]
In Vitro
When HepG2 cells are cotreated with atRA and Talarozole (1 μM), 4-OH-RA and 4-oxo-RA formation is significantly decreased[2].
In Vivo
A maximum 84% inhibition of CYP26 activity at 0.5 hours post-dose is predicted based on Talarozole (TLZ) Cmaxof 80 nM and a Kiof 1 nM following a single dose of Talarozole. Due to the short Talarozole half-life (2.2 hrs) CYP26 activity is predicted to return to 100% by 12 hours. In agreement with the predictions,atRA concentrations are increased by 82, 63 and 60% at 4 hours post-dose in the serum, liver and testes, respectively, and concentrations returned to baseline by 24 hours. Following multiple doses of Talarozole, liver CYP26 mRNA and activity are increased suggesting autoinduction of CYP26 due to increasedatRA concentrations. In agreement,atRA concentrations are elevated in serum and liver at all timepoints measured. This increase inatRA concentrations is associated with increased mRNA of the mitochondrial biogenesis markers PGC-1β and NRF-1 in comparison to control mice[3].
Clinical Trial
Stiefel, a GSK Company-GlaxoSmithKline
Acne
September 2004
Phase 2
Stiefel, a GSK Company-GlaxoSmithKline
Psoriasis
June 2006
Phase 2
Stiefel, a GSK Company-GlaxoSmithKline
Cutaneous Inflammation
November 2006
Phase 1
Stiefel, a GSK Company-GlaxoSmithKline
Psoriasis
April 2004
Phase 2
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References
