| Chemical Properties | Back Directory | [Boiling point ]
627.3±55.0 °C(Predicted) | [density ]
1.34±0.1 g/cm3(Predicted) | [form ]
Solid | [pka]
5.15±0.20(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
PF-07258669 is an orally active melanocortin-4 receptor (MC4R) antagonist that antagonizes MC4R with an IC50 of 13 nM (Ki=0.46 nM). PF-07258669 can be used for the research of cachexia, anorexia, or anorexia nervosa[1]. | [in vivo]
PF-07258669 (0.3-10 mg/kg, po, twice a day for 22 days) regulates appetite and food intake, increases body weight in aged rats models[2].
PF-07258669 exhibits good pharmacokinetic properties in rats and dogs with an oral bioavailability of 93% in dogs[2].
Pharmacokinetic Analysis of PF-07258669[1]
| species | Dose (mg/kg) | route | CLp (mL/min/kg) | Vss (L/kg) | T1/2 (h) | Tmax (h) | Cmax (ng/mL) | AUCinf (ng·h/mL) | AUClast (ng·h/mL)) | F (%) | | rat | 1 | iv | 21 | 0.95 | 1.0 | - | - | 785 | 780 | - | | rat | 5 | oral | - | - | 0.98 | 0.5 | 600 | 1120 | 1110 | 28 | | dog | 1 | iv | 11 | 1.3 | 2.3 | - | - | 1660 | 1640 | - | | dog | 5 | oral | - | - | 3.6 | 0.38 | 1470 | 4610 | 4580 | 93 |
| Animal Model: | Aged rats models[2] | | Dosage: | 0.3-10 mg/kg | | Administration: | po, twice a day for 22 days | | Result: | Increased daily food intake and body weight. |
| [IC 50]
MC4R: 13 nM (IC50); MC4R: 0.46 nM (Ki) | [References]
[1] Christopher Ryan BUTLER, et al. Spiro compounds as melanocortin 4 receptor antagonists and uses thereof. Patent. WO2021250541A1.
[2] Garnsey MR, et al., Discovery of the Potent and Selective MC4R Antagonist PF-07258669 for the Potential Treatment of Appetite Loss. J Med Chem. 2023 Mar 9;66(5):3195-3211. DOI:10.1021/acs.jmedchem.2c02012 |
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