Danuglipron

• CAT Number: I046044
• CAS Number: 2230198-02-2
• Molecular Formula: C31H30FN5O4
• Molecular Weight: 555.60
• Purity: ≥95%
• Synonyms: 2-[[4-[6-[(4-cyano-2-fluorophenyl)methoxy]pyridin-2-yl]piperidin-1-yl]methyl]-3-[[(2S)-oxetan-2-yl]methyl]benzimidazole-5-carboxylic acid
• InChI: InChI=1S/C31H30FN5O4/c32-25-14-20(16-33)4-5-23(25)19-41-30-3-1-2-26(35-30)21-8-11-36(12-9-21)18-29-34-27-7-6-22(31(38)39)15-28(27)37(29)17-24-10-13-40-24/h1-7,14-15,21,24H,8-13,17-19H2,(H,38,39)/t24-/m0/s1
• InChIKey: HYBAKUMPISVZQP-DEOSSOPVSA-N
• SMILES: C1CN(CCC1C2=NC(=CC=C2)OCC3=C(C=C(C=C3)C#N)F)CC4=NC5=C(N4CC6CCO6)C=C(C=C5)C(=O)O

Danuglipron (PF-06882961) is an orally active glucagon-like peptide-1 receptor (GLP-1R) agonist. Danuglipron has the potential for type 2 diabetes research[1][2].
Danuglipron (PF-06882961) shows agonist activities at both the cAMP and βArr pathways. Danuglipron is a full agonist (EC50 of 13 nM) in the CS cAMP assay. Danuglipron is a partial agonist in recruiting βArr2 (EC50 of 490 nM)[1].
Danuglipron (PF-06882961; 10 mg/kg; po; a single dose) reduces blood glucose levels following intraperitoneal glucose tolerance test (IPGTT) in the hGLP-1R mouse model[2].
Pharmacokinetic Parameters of Danuglipron in Male Wistar rats and Male cynomolgus monkeys[1].

1.19

Species
Dose (mg/kg)
Cmax (ng/mL)
Tmax (h)
AUC0–∞ (ng h/mL)
CLp (mL/min/kg)
Vdss (L/kg)
t1/2 (h)
Oral F (%)

rat
1.0 (iv)
–
–
296 ± 39.8
57.3 ± 8.68
0.86 ± 0.38
1.13 ± 0.84
–

rat
5.0 (po)
141
0.5
168
–
–
0.63
11

rat
100 (po)
2820
0.75
11900
–
–
2.37
39

monkey
1.0 (iv)
–
–
1240
13.8
0.266
1.89
–

monkey
5.0 (po)
68.7
1.5
303
–
–
6.92
5.0

monkey
100 (po)
1150 ± 715
3.3 ± 2.5
11000 ± 3500
–
–
6.37
9.0

Reference

[1]. David A Griffithm, et al. A Small-Molecule Oral Agonist of the Human Glucagon-like Peptide-1 Receptor. J Med Chem. 2022 Jun 23;65(12):8208-8226.
 [Content Brief]

[2]. W. GUO, et al. Preclinical pharmacology of low molecular weight GLP-1 receptor agonist XW014.