PF-06446846

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

PF－06446846 是一种有效的选择性 PCSK9 抑制剂 PF-06446846 口服给药后可降低大鼠血浆 PCSK9 和总胆固醇水平。

PF?06446846 is a potent and selective PCSK9 inhibitor?PF-06446846 reduces plasma PCSK9 and total cholesterol levels in rats following oral dosing.?PF-06446846 is highly selective for the inhibition of PCSK9 translation.?The mechanism of action employed by PF-06446846 reveals a previously unexpected tunability of the human ribosome that allows small molecules to specifically block translation of individual transcripts.

PF-06446846 inhibits the secretion of PCSK9 by Huh7 cells with an IC50 of 0.3 μM.PF-06446846 inhibits PCSK9(1–35)-luciferase expression with an IC50 of 2 μM.PF-06446846 (Compound 7f) shows rat bone marrow and human CD34+ toxicity. Cell Cytotoxicity Assay Cell Line:Rat bone marrow lineage (?) cell and CD34+ cell Concentration:0-20 μM Incubation Time:72 h Result:Showed cytotoxicity with IC50 values of 2.9 μM and 2.7 μM against rat Lin(?) and human CD34+, respectively.

PF-06446846 reduces circulating PCSK9 and total plasma cholesterol levels in vivo without obvious toxicity. Animal Model:Male Sprague-Dawley (Crl:CD [SD] rats, five per group; 6–8 wk old at initiation of dosing)Dosage:5, 15, and 50 mg/kg Administration:Oral administration, daily, 14 days Result:Reduced plasma PCSK9, total plasma cholesterol, and LDL-C (low-density lipoprotein cholesterol) in a dose-dependent manner without obvious toxicity.

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Others

Other Targets

PCSK9

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1632250-49-7

433.9

C22H20ClN7O

>98% (HPLC)

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Clc1cccnc1N([C@@H]1CCCNC1)C(=O)c1ccc(cc1)-n1nnc2cccnc12

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(-20℃)

With Ice Pack

≥ 2 years