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PF-915275
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
PF-915275图片
CAS NO:857290-04-1
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW) 350.39
Formula C18H14N4O2S
CAS No. 857290-04-1
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: ≥ 31 mg/mL
Water: <1 mg/mL
Ethanol: <1 mg/mL
SMILES O=S(C1=CC=C(C2=CC=C(C#N)C=C2)C=C1)(NC3=NC(N)=CC=C3)=O
Synonyms PF915275; PF 915275; PF-915275
实验参考方法
In Vitro

In vitro activity: PF-915275 is a novel and selective inhibitor of human 11β-hydroxysteroid dehydrogenase type 1 (11betaHSD1) with Ki of<1 nM and good pharmacokinetics. 11betaHSD1 play a key role in ligand-induced activation of the GR through the production of cortisol. Evidence from genetically modified mice suggests that inhibition of 11betaHSD1 might be a therapeutic approach to treat the metabolic syndrome. PF-915275 maintains potency in our cellular assay against human 11βHSD1 (HEK293, EC50 = 5 nM) and is selective against human 11βHSD2 (HEK293, 1.5% inhibition 10 μM). PF-915275 displays only weak affinity for the rodent choline transporter (Ki = 9.6 μM) and the hamster melatonin MT3 receptor (Ki = 9.6 μM) in the Cerep Bioprint screening panel. PF-915275 has good in vitro pharmacokinetic properties.


Kinase Assay: PF-915275 maintains potency in our cellular assay against human 11βHSD1 (HEK293, EC50 = 5 nM) and is selective against human 11βHSD2 (HEK293, 1.5% inhibition 10 μM). PF-915275 displays only weak affinity for the rodent choline transporter (Ki = 9.6 μM) and the hamster melatonin MT3 receptor (Ki = 9.6 μM) in the Cerep Bioprint screening panel.

In VivoAdult cynomolgus monkeys were administered either vehicle or various doses of PF-915275 followed by a 10-mg/kg dose of prednisone. Prednisone conversion to prednisolone and the concentrations of PF-915275 were measured by liquid chromatography/tandem mass spectrometry. PF-915275 dose-dependently inhibited 11betaHSD1-mediated conversion of prednisone to prednisolone, with a maximum of 87% inhibition at a 3-mg/kg dose. An exposure-response relationship was demonstrated, with an estimated EC(50) of 391 nM (total) and 17 nM (free). Insulin levels were also reduced in a dose-related manner. These results should enable the development of a biomarker for evaluating target modulation in humans that will aid in identifying 11betaHSD1 inhibitors to treat diabetes and other related metabolic diseases.
Animal model Adult cynomolgus monkey
Formulation & Dosage 10-mg/kg
References J Pharmacol Exp Ther. 2008 Jan;324(1):299-305.