PF-06427878
PF-06427878 is an orally active, selective liver-targeted diacylglycerol acyltransferase 2 (DGAT2) inhibitor with IC50s of 99 nM and 202 nM for human and rat DGAT2, respectively. PF-06427878 shows greater than 470-fold selectivity for DGAT2 over DGAT1, MGAT1, MGAT2 and MGAT3. PF-06427878 can improve liver steatosis and function. PF-06427878 can be used for the study of nonalcoholic fatty liver diseases.
For research use only. We do not sell to patients.
- CAS No.: 1809064-23-0
- Formula: C26H28N4O5
- Molecular Weight:476.52
-
Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
-
CAS No. 1809064-23-0
-
Molecular Weight 476.52
-
Formula C26H28N4O5
-
SMILES
O=C(O)C1=CC=CC(CNC(C2=CN=C(N3C[C@H](OC4=CC=CC=C4OCC)CCC3)N=C2)=O)=C1
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
-
Research Protocol for Metabolic Diseases
AMP-activated protein kinase, AMPK, is a conserved cellular energy sensor that responds to reduced cellular energy status and coordinates metabolism by increasing ATP-generating catabolic pathways while suppressing ATP-consuming anabolic processes. In metabolic disease research, the AMPK pathway is experimentally relevant because it regulates hepatic lipid synthesis, fatty acid oxidation, glucose production, skeletal-muscle glucose disposal, mTORC1-linked biosynthesis, autophagy, mitochondrial homeostasis, and whole-body energy balance. The central pathway logic is that energy stress, metformin, exercise-like stimulation, or direct AMPK activators increase AMPKα Thr172 phosphorylation and downstream substrate phosphorylation, including ACC and RAPTOR. Phosphorylation of ACC suppresses lipogenesis and supports fatty acid oxidation, whereas phosphorylation of RAPTOR suppresses mTORC1 signaling and links cellular energy status to growth and protein synthesis control. The pathway is linked
-
Liver Histomorphometry
Liver histomorphometry is a quantitative histological approach used to measure structural alterations in hepatic tissue, including parenchymal loss, steatosis, fibrosis, and vascular remodeling, by combining stained tissue section analysis with stereological or computerized image-based measurements. Classical morphometric frameworks quantify volume fractions of liver compartments and fibrotic regions using systematic sampling and image analysis, enabling objective comparison of pathological changes across experimental groups. These approaches are widely applied in liver cirrhosis and fibrosis studies to reduce subjectivity in histological scoring and improve reproducibility of tissue evaluation. Recent methodological advances integrate automated image analysis and radiomics-based extraction of histological features from standard liver stains (e. g. , H&E and fibrotic stains), enabling quantitative correlation between morphometric features and fibrosis stages in non-alcoholic fatty live
Purity & Documentation
References
[1]. Amin NB, et al. Targeting diacylglycerol acyltransferase 2 for the treatment of nonalcoholic steatohepatitis. Sci Transl Med. 2019 Nov 27;11(520):eaav9701. [Content Brief]
[2]. Sharma R, et al. Mitigating a Bioactivation Liability with an Azetidine-Based Inhibitor of Diacylglycerol Acyltransferase 2 (DGAT2) En Route to the Discovery of the Clinical Candidate Ervogastat. Chem Res Toxicol. 2023 Jun 19;36(6):934-946. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)