CCX140 1100318-47-5 GlpBio

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Product Data Sheet

Product Name: Cat. No.: Chemical Name:

CCX140 GC31330

CHEMICAL PROPERTIES Cas No.: 1100318-47-5 Molecular Formula: Molecular Weight: Storage: Solubility:

Chemical Structure:

C20H13ClF3N5O3S 495.86 Powder

Soluble in DMSO

Background

CCX140 is a potent CCR2 antagonist.

CCX140−B potently inhibits CCL2−induced chemotaxis of purified human blood monocytes with IC50 values of 8 nM in buffer and 200 nM in the presence of 100% human serum. CCX140−B also inhibits CCL2−induced Ca2+ mobilization in monocytes with an IC50 value of 3 nM. CCX140−B inhibits the binding of 125I−CCL2 to monocytes with an IC50 value of 17 nM. CCX140−B has a Kd value of 2.3 nM toward hCCR2. CCX140−B also inhibits monocyte chemotaxis mediated by the other CCR2 ligands: CCL8/MCP−2, CCL7/MCP−3, and CCL13/MCP−4[1].

Treatment of hCCR2 KI mice with CCX140−B causes a dose−dependent reduction in the number of peritoneal leukocytes after thioglycollate challenge: CCX140−B strongly blocks leukocyte infiltration at 30 mg/kg, partially blocks leukocyte infiltration at 10 mg/kg, and fails to block leukocyte infiltration at 3 mg/kg. In DIO hCCR2 KI mice, treatment with 100 mg/kg CCX140−B blocks the progressive increase in UAER and ACR. CCX140−B maintains lower UAER and ACR values during the entire 8−wk dosing regimen[1]. In DIO mice, the CCR2 antagonist completely blocks the recruitment of inflammatory macrophages to visceral adipose tissue. The mice exhibit reduced hyperglycemia and insulinemia, improved insulin sensitivity, increased circulating adiponectin levels, decreased pancreatic islet size and increased islet number. It also reduces urine output, glucose excretion, hepatic glycogen and triglyceride content and glucose 6−phosphatase levels[2]. References:

[1]. Sullivan T, et al. CCR2 antagonist CCX140-B provides renal and glycemic benefits in diabetic transgenic human CCR2 knockin mice. Am J Physiol Renal Physiol. 2013 Nov 1;305(9):F1288-97.

[2]. Sullivan TJ, et al. Experimental evidence for the use of CCR2 antagonists in the treatment of type 2 diabetes. Metabolism. 2013 Nov;62(11):1623-32.

Research Update

1. Effect of Hydrofluoric Acid Concentration and Etching Time on Bond Strength to Lithium Disilicate Glass Ceramic. Oper Dent. 2017 Nov/Dec;42(6):606-615. doi: 10.2341/16-215-L. Epub 2017 Jul 14. PMID:28708007 Abstract

The aim of this study was to evaluate the influence of different concentrations of hydrofluoric acid (HF) associated with varied etching times on the microshear bond strength (μSBS) of a resin cement to a lithium disilicate glass ceramic. Two hundred seventy-five ceramic blocks (IPS e.max Press [EMX], Ivoclar Vivadent), measuring 8 mm × 3 mm thickness, were randomly distributed into five groups according to the HF concentrations (n=50): 1%, 2.5%, 5%, 7.5%, and 10%.

2. Does acid etching morphologically and chemically affect lithium disilicate glass ceramic surfaces? J Appl Biomater Funct Mater. 2017 Jan 26;15(1):e93-e100. doi: 10.5301/jabfm.5000303. PMID:27647389 Abstract

BACKGROUND: This study evaluated the surface morphology, chemical composition and adhesiveness of lithium disilicate glass ceramic after acid etching with hydrofluoric acid or phosphoric acid.METHODS: Lithium disilicate glass ceramic specimens polished by 600-grit silicon carbide paper were subjected to one or a combination of these surface treatments: airborne particle abrasion with 50-μm alumina (AA), etching with 5% hydrofluoric acid (HF) or 36% phosphoric acid (Phos), and application of silane coupling agent (Si). 3. Fatigue failure load of feldspathic ceramic crowns after hydrofluoric acid etching at different concentrations. J Prosthet Dent. 2018 Feb;119(2):278-285. doi: 10.1016/j.prosdent.2017.03.021. Epub 2017 May 26. PMID:28552291 Abstract

STATEMENT OF PROBLEM: Hydrofluoric acid etching modifies the cementation surface of ceramic restorations, which is the same surface where failure is initiated. Information regarding the influence of hydrofluoric acid etching on the cyclic loads to failure of ceramic crowns is lacking.PURPOSE: The purpose of this in vitro study was to evaluate the influence of different hydrofluoric acid concentrations on the fatigue failure loads of feldspathic ceramic crowns.