PF-06446846 hydrochloride

• CAT Number: I014768
• CAS Number: 1632250-50-0
• Molecular Formula: C22H21Cl2N7O
• Molecular Weight: 470.35
• Purity: ≥95%
• Synonyms: N-(3-chloropyridin-2-yl)-N-[(3R)-piperidin-3-yl]-4-(triazolo[4,5-b]pyridin-3-yl)benzamide;hydrochloride
• InChI: InChI=1S/C22H20ClN7O.ClH/c23-18-5-2-12-25-20(18)29(17-4-1-11-24-14-17)22(31)15-7-9-16(10-8-15)30-21-19(27-28-30)6-3-13-26-21;/h2-3,5-10,12-13,17,24H,1,4,11,14H2;1H/t17-;/m1./s1
• InChIKey: AQSJYIVIWBIHOU-UNTBIKODSA-N
• SMILES: C1CC(CNC1)N(C2=C(C=CC=N2)Cl)C(=O)C3=CC=C(C=C3)N4C5=C(C=CC=N5)N=N4.Cl

PF-06446846 hydrochloride is an orally active and highly selective inhibitor of translation of Proprotein convertase subtilisin/kexin type 9 (PCSK9). PF-06446846 hydrochloride inhibits PCSK9 by inducing the ribosome to stall around codon 34[1].
PF-06446846 inhibits the secretion of PCSK9 by Huh7 cells with an IC50 of 0.3 μM[1].
PF-06446846 (oral gavage; 5-50 mg/kg/day for 14 days) lowers plasma PCSK9 in a dose-dependent manner and lowers total cholesterol levels[1].

Reference

[1]. Lintner NG, et al. Selective stalling of human translation through small-molecule engagement of the ribosome nascent chain. PLoS Biol. 2017 Mar 21;15(3):e2001882.
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