ChemicalBook CAS DataBase List 2140301-98-8

2140301-98-8

Name	PF-04634817 succinate
CAS	2140301-98-8
Molecular Formula	C29H42F3N5O7
MDL Number	MFCD29079008
Molecular Weight	629.68
MOL File	2140301-98-8.mol

Chemical Properties

storage temp.	room temp
solubility	DMSO: 2mg/mL, clear
form	Solid
color	White to off-white
InChIKey	MCRWZBYTLVCCJJ-DKALBXGISA-N
SMILES	CO[C@H]1[C@@H](N[C@@H]2CC[C@@](C(N3C[C@@]4([H])N(C5=NC=NC(C(F)(F)F)=C5)C[C@]3([H])C4)=O)(C(C)C)C2)CCOC1

Safety Data

WGK Germany	WGK 3
Storage Class	11 - Combustible Solids

Hazard Information

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

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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