PF-06446846

SKU: orb1219809

Description

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.

Key Properties

• CAS Number: 1632250-49-7
• MW: 433.9
• Purity: >98% (HPLC)
• Formula: C₂₂H₂₀ClN₇O
• SMILES: Clc1cccnc1N([C@@H]1CCCNC1)C(=O)c1ccc(cc1)-n1nnc2cccnc12
• Target: PCSK9

Bioactivity

• In Vivo:
  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.
• In Vitro:
  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.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Quick Database Links

Gene Symbol

PCSK9