PF-06882961

Product NamePF-06882961
CAS2230198-02-2
MFC31H30FN5O4
MW555.6
EINECS
MOL File2230198-02-2.mol

Chemical Properties

Boiling point	782.6±60.0 °C(Predicted)
Density	1.39±0.1 g/cm3(Predicted)
storage temp.	Store at -20°C
solubility	DMSO:10.0(Max Conc. mg/mL);18.0(Max Conc. mM) Ethanol:100.0(Max Conc. mg/mL);179.98(Max Conc. mM)
form	Solid powder
pka	3.41±0.30(Predicted)
InChIKey	HYBAKUMPISVZQP-DEOSSOPVSA-N
SMILES	C1(CN2CCC(C3=NC(OCC4=CC=C(C#N)C=C4F)=CC=C3)CC2)N(C[C@@H]2CCO2)C2=CC(C(O)=O)=CC=C2N=1

Usage And Synthesis

Uses

PF-06882961 is a potent, orally bioavailable glucagon-like peptide-1 receptor agonist (GLP-1R) agonist. It has blood glucose lowering and weight loss properties and is used to treat type 2 diabetes (T2D) and obesity.

in vitro

For example, a methylene-linked oxetane increased potency ~100-fold relative to the methyl substituent of 5, leading to the identification of PF-06882961, which is a full agonist (EC50 = 13 nM) in the CS cAMP assay. PF-06882961 also incorporates a nitrile replacement for the chloride in the benzyl ether region, which served to reduce CLint in HLM as well as in human hepatocytes.
Reference: J Med Chem. 2022 Jun 23;65(12):8208-8226. https://pubmed.ncbi.nlm.nih.gov/35647711/

in vivo

Intravenous infusion of PF-06882961 during the IVGTT led to an increase in insulin secretion and the rate of glucose disappearance (K-value). Enhancement of glucose-stimulated insulin secretion by PF-06882961 was concentration-dependent and was also observed following oral dosing with similar efficacy when compared to administration by IV infusion. Once-daily administration of PF-06882961 for 2 days also inhibited food intake compared to vehicle-treated monkeys.
Reference: J Med Chem. 2022 Jun 23;65(12):8208-8226. https://pubmed.ncbi.nlm.nih.gov/35647711/

target

PF-06882961, a non-peptide agonist, activates the canonical G protein signaling activity only in the Glucagon-like peptide-1 (GLP-1) receptor with Trp33ECD.