| Identification | Back Directory | [Name]
PF-04634817 succinate | [CAS]
2140301-98-8 | [Synonyms]
PF 4634817 succinate
PF-04634817 succinate
PF 04634817 succinate,PF04634817 succinate | [Molecular Formula]
C29H42F3N5O7 | [MDL Number]
MFCD29079008 | [MOL File]
2140301-98-8.mol | [Molecular Weight]
629.68 |
| Hazard Information | Back Directory | [Uses]
PF-0463481 succinate 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 succinate is safe and well-tolerated and has the potential for the study of diabetic nephropathy[3]. | [Biological Activity]
Orally availablepotent and selective CCR2/5 receptor antagonist | [in vivo]
PF-04634817 succinate (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
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| [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 |
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