PF-06424439
- Product Name
- PF-06424439
- CAS No.
- 1469284-78-3
- Chemical Name
- PF-06424439
- Synonyms
- Methanone, [(3R)-1-[2-[1-(4-chloro-1H-pyrazol-1-yl)cyclopropyl]-3H-imidazo[4,5-b]pyridin-5-yl]-3-piperidinyl]-1-pyrrolidinyl-;PF06424439,Diglyceride acyltransferase,mono- acylglycerol acyltransferase,Inhibitor,acyl-CoA:cholesterol acyltransferase,Diacylglycerol acyltransferase,PF 06424439,PF-06424439,Acyltransferase,inhibit
- CBNumber
- CB53355456
- Molecular Formula
- C22H26ClN7O
- Formula Weight
- 439.94
- MOL File
- 1469284-78-3.mol
PF-06424439 Property
- Boiling point:
- 752.8±60.0 °C(Predicted)
- Density
- 1.57±0.1 g/cm3(Predicted)
- solubility
- DMSO:70.0(Max Conc. mg/mL);159.11(Max Conc. mM)
H2O:70.0(Max Conc. mg/mL);159.11(Max Conc. mM) - form
- Solid
- pka
- 12.11±0.40(Predicted)
- color
- White to off-white
PF-06424439 Chemical Properties,Usage,Production
Description
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.
Uses
PF-06424439 is an oral, potent and selective imidazopyridine diacylglycerol acyltransferase 2 (DGAT2) inhibitor with an IC50 of 14 nM[1]. PF-06424439 is slowly reversible, time-dependent inhibitor, which inhibits DGAT2 in a noncompetitive mode with respect to the acyl-CoA substrate[2].
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.
References
[1] Futatsugi K, et al. Discovery and Optimization of Imidazopyridine-Based Inhibitors of Diacylglycerol Acyltransferase 2 (DGAT2). J Med Chem. 2015 Sep 24;58(18):7173-85. DOI:10.1021/acs.jmedchem.5b01006
[2] Pabst B, et al. Mechanistic Characterization of Long Residence Time Inhibitors of Diacylglycerol Acyltransferase 2 (DGAT2). Biochemistry. 2018 Dec 26;57(51):6997-7010. DOI:10.1021/acs.biochem.8b01096
PF-06424439 Preparation Products And Raw materials
Raw materials
Preparation Products
PF-06424439 Suppliers
- Tel
- 13816613772
- Fax
- QQ: 12922499
- huahero21@sina.com
- Country
- China
- ProdList
- 2391
- Advantage
- 55
- Tel
- Fax
- -
- 13006575422@163.com
- Country
- China
- ProdList
- 6355
- Advantage
- 58
- Tel
- 15911056312
- liming@bio-fount.com
- Country
- China
- ProdList
- 9729
- Advantage
- 58
- Tel
- +1-781-999-5354; +17819995354
- marketing@targetmol.com
- Country
- United States
- ProdList
- 32435
- Advantage
- 58
- Tel
- 18051384581
- sales@chemhifuture.com
- Country
- China
- ProdList
- 3000
- Advantage
- 58
- Tel
- 4008200310
- marketing@tsbiochem.com
- Country
- China
- ProdList
- 24961
- Advantage
- 58
- Tel
- 025-85560043 15850508050
- Fax
- 025-85563444
- cindy.huang@synzest.com
- Country
- China
- ProdList
- 12000
- Advantage
- 58
- Tel
- 025-58851090 17714375163
- 2881759498@qq.com
- Country
- China
- ProdList
- 13011
- Advantage
- 58
- Tel
- 400-6111-883 13121892008
- marketing@yeasen.com
- Country
- China
- ProdList
- 6173
- Advantage
- 58
- Tel
- 51288865780
- sales@biosynth.com
- Country
- China
- ProdList
- 6051
- Advantage
- 58