PF-04634817 succinate 

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].

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

629.67

C₂₉H₄₂F₃N₅O₇

2140301-98-8

Solid

White to off-white

O=C(N1[C@@]2([H])C[C@@]([H])(C1)N(C3=NC=NC(C(F)(F)F)=C3)C2)[C@@]4(C[C@@H](CC4)N[C@@H]5[C@@H](COCC5)OC)C(C)C.OC(CCC(O)=O)=O

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

• [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.  [Content Brief]

  [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.  [Content Brief]

  [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.  [Content Brief]