| Identification | Back Directory | [Name]
PF-06446846 | [CAS]
1632250-49-7 | [Synonyms]
PF-6446846
PF-06446846
Threonine proteases,PF06446846,Inhibitor,80S ribosome,Selective,PF 06446846,Ser/Thr Protease,Serine proteases,Rat bone marrow,Huh7,inhibit,Serine endopeptidases,PF-06446846 | [Molecular Formula]
C22H20ClN7O | [MDL Number]
MFCD32182630 | [MOL File]
1632250-49-7.mol | [Molecular Weight]
433.89 |
| Chemical Properties | Back Directory | [Boiling point ]
655.5±65.0 °C(Predicted) | [density ]
1.46±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO: 87 mg/mL (200.51 mM);Ethanol: 87 mg/mL (200.51 mM) | [pka]
8.69±0.10(Predicted) | [Water Solubility ]
Water: Insoluble |
| Hazard Information | Back Directory | [Uses]
PF-06446846 is an orally active proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. PF-06446846 directly and selectively inhibits translation of PCSK9 by stalling the 80S ribosome in the proximity of codon region[1]. | [Definition]
ChEBI: PF-06446846 is a triazolopyridine that is 3H-[1,2,3]triazolo[4,5-b]pyridine substituted by a 4-{(3-chloropyridin-2-yl)[(3R)-piperidin-3-yl]carbamoyl}phenyl group at position 3. It is a potent inhibitor of PCSK9. It has a role as an antilipemic drug and an EC 3.4.21.61 (kexin) inhibitor. It is a monochloropyridine, a member of piperidines, a tertiary carboxamide, a member of benzamides and a triazolopyridine. | [in vivo]
PF-06446846 reduces circulating PCSK9 and total plasma cholesterol levels in vivo without obvious toxicity[1]. | Animal Model: | Male Sprague-Dawley (Crl:CD [SD] rats, five per group; 6–8 wk old at initiation of dosing)[1] | | 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. |
| [References]
[1] Nathanael G Lintner, et al. Selective stalling of human translation through small-molecule engagement of the ribosome nascent chain. PLoS Biol. 2018 Apr 17;16(4):e1002628.
[2] Allyn T. Londregan, et al. Small Molecule Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors: Hit to Lead Optimization of Systemic Agents. J Med Chem. 2018 Jul 12;61(13):5704-5718. DOI:10.1021/acs.jmedchem.8b00650 |
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