PF-06424439 Struktur

PF-06424439

Bezeichnung:PF-06424439

CAS-Nr1469284-78-3

Englisch Name:PF-06424439

CBNumberCB53355456

SummenformelC22H26ClN7O

Molgewicht439.94

MOL-Datei1469284-78-3.mol

PF-06424439 physikalisch-chemischer Eigenschaften

Siedepunkt	752.8±60.0 °C(Predicted)
Dichte	1.57±0.1 g/cm3(Predicted)
Löslichkeit	DMSO:70.0(Max Conc. mg/mL);159.11(Max Conc. mM) H2O:70.0(Max Conc. mg/mL);159.11(Max Conc. mM)
pka	12.11±0.40(Predicted)

PF-06424439 Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
PF-06424439 is a potent and selective Diacylglycerol Acyltransferase 2 ( DGAT2) inhibitor with DGAT2 IC50 ± SEM (nM) (humarat/dog) 14 ± 1/38 ± 4/16 ± 1. PF-06424439 demonstrated excellent ADMET properties and decreased circulating and hepatic lipids when orally administered to dyslipidemic rodent models. PF-06424439 inhibited DGAT2 of different species (human, rat, and dog) with similar potency. Among related acyltransferases, no significant inhibition was observed for PF-06424439 (up to 50 μM) against human MGAT2 or MGAT3, DGAT1, or mouse MGAT1, indicating a high selectivity (>2000-fold) against these enzymes.
in vitro
The effect of PF-06424439, a selective DGAT2 inhibitor, on MCF7 breast cancer cells exposed to X-rays was evaluated. The results demonstrated that 72 h of PF-06424439 treatment reduced LD (lipid droplets) content and inhibited cell migration, without affecting cell proliferation. Interestingly, PF-06424439 pre-treatment followed by radiation was able to enhance radiosensitivity of MCF7 cells. These findings suggest that PF-06424439 pre-treatment coupled to X-ray exposure might potentiate breast cancer cell radiosensitivity and potentially improve the radiotherapy effectiveness. _x000D_ _x000D_ Reference: Int J Mol Sci. 2021 Sep 18;22(18):10102. https://pubmed.ncbi.nlm.nih.gov/34576263/
in vivo
The effects of DGAT1 and DGAT2 inhibition, alone or in combination, on dietary TAG absorption and diarrhea in mice were investigated by using a selective DGAT1 inhibitor (PF-04620110) and DGAT2 inhibitor (PF-06424439). To further understand relationship between diarrhea and changes in DGAT activity, we examined dose‐dependent effects of DGAT inhibitors in mice. Simultaneous administration of a lower‐dose DGAT1 (0.03 mg/kg) inhibitor, which did not produce maximal effects on intestinal TAG secretion, and the DGAT2 inhibitors significantly decreased plasma radioactivity. These findings suggest that DGAT-mediated intestinal TAG synthesis is a vital step for maintaining intestinal barrier integrity under HFD (high-fat diet) feeding._x000D_ _x000D_ Reference: Physiol Rep. 2020 Aug;8(15):e14542. https://pubmed.ncbi.nlm.nih.gov/32786057/
target
PF-06424439 is a selective imidazopyridine diacylglycerol acyltransferase 2 (DGAT2) inhibitor with an IC50 of 14 nM that is a slowly reversible, time-dependent inhibitor, which inhibits DGAT2 in a noncompetitive mode with respect to the acyl-CoA substrate.

PF-06424439 Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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