PF-4634817
PF-4634817 Basic information
- Product Name:
- PF-4634817
- Synonyms:
-
- PF-04634817
- PF-4634817
- D-erythro-Pentitol, 1,5-anhydro-2,3-dideoxy-4-O-methyl-3-[[(1R,3S)-3-(1-methylethyl)-3-[[(1S,4S)-5-[6-(trifluoromethyl)-4-pyrimidinyl]-2,5-diazabicyclo[2.2.1]hept-2-yl]carbonyl]cyclopentyl]amino]-
- PF 04634817,PF04634817
- CAS:
- 1228111-63-4
- MF:
- C25H36F3N5O3
- MW:
- 511.58
- Mol File:
- 1228111-63-4.mol
PF-4634817 Chemical Properties
- Boiling point:
- 630.3±55.0 °C(Predicted)
- Density
- 1.30±0.1 g/cm3(Predicted)
- storage temp.
- Store at -20°C
- solubility
- DMSO: 50 mg/mL (97.74 mM)
- form
- Solid
- pka
- 8.62±0.40(Predicted)
- color
- White to off-white
PF-4634817 Usage And Synthesis
Uses
PF-0463481 is a potent and orally active dual CCR2/CCR5 antagonist with comparable human and rodent CCR2 potency (rat IC50=20.8 nM), and displays 10-20 fold less rodent CCR5 potency (rat IC50=470 nM). PF-0463481 is safe and well-tolerated and has the potential for the study of diabetic nephropathy[3].
in vivo
PF-04634817 (oral administration; 30 mg/kg; once daily; 31 days intervention (weeks 2-15 after Streptozotocin)) intervention at the onset of diabetes (week 2) has no impact on the fasting blood glucose levels in diabetic Nos3-/- 221 mice. The development of diabetes results in a marked increase in the levels of glycated haemoglobin (HbA1c) in Nos3-/- mice. Early intervention with PF-04634817 induces an additional increase in glycated hemoglobin (HbA1c) levels[1].
| Animal Model: | Nos3-/- mice on the C57BL/6 background[1] |
| Dosage: | 30 mg/kg |
| Administration: | Oral administration; once daily; 31 days intervention (weeks 2-15 after Streptozotocin) |
| Result: | Had no impact on the fasting blood glucose levels, but induced an additional increase in HbA1c levels. |
IC 50
Rat CCR2: 20.8 nM (IC50); CCR5: 470 nM (IC50)
References
[1] Tesch GH, et al. Combined inhibition of CCR2 and ACE provides added protection against progression of diabetic nephropathy in?Nos3-deficient mice.Am J Physiol Renal Physiol.?2019 Dec 1;317(6):F1439-F1449. DOI:10.1152/ajprenal.00340.2019
[2] Gale JD, et al. A CCR2/5 Inhibitor, PF-04634817, Is Inferior to Monthly Ranibizumab in the Treatment of Diabetic Macular Edema. Invest Ophthalmol Vis Sci. 2018 May 1;59(6):2659-2669. DOI:10.1167/iovs.17-22731
[3] Gale JD, et al. Effect of PF-04634817, an Oral CCR2/5 Chemokine Receptor Antagonist, on Albuminuria in Adults with Overt Diabetic Nephropathy. Kidney Int Rep. 2018 Aug 3;3(6):1316-1327. DOI:10.1016/j.ekir.2018.07.010
PF-4634817Supplier
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