Characterization of CCX140-B, an orally bioavailable antagonist of the CCR2 chemokine receptor, for the treatment of type 2 diabetes and associated complications

Abstract

The following manuscript was published as a Fast Forward article on February 29, 2012: Sullivan TJ, Dairaghi DJ, Krasinski A, Miao Z, Wang Y, Zhao BN, Baumgart T, Berahovich R, Ertl LS, Pennell A, Seitz L, Miao S, Ungashe S, Wei Z, Johnson D, Boring L, Tsou C-L, Charo IF, Bekker P, Schall TJ, and Jaen JC, Characterization of CCX140-B, an orally bioavailable antagonist of the CCR2 chemokine receptor, for the treatment of type 2 diabetes and associated complications. J Pharmacol Exp Ther jpet.111.190918; doi:10.1124/jpet.111.190918 It was later found that the chemical identity of a compound cited in the article, CCX140-B, was not sufficiently disclosed. The authors are unable, at this time, to provide the chemical identity of CCX140-B in accordance with the editorial policies of The Journal of Pharmacology and Experimental Therapeutics. As a result, the authors have voluntarily withdrawn this manuscript from publication. We apologize for any inconvenience this may cause JPET's readers.

Targeting chemokines in proteinuria-induced renal disease

“…A number of small-molecule CCR2 antagonists have advanced to clinical trials in humans, with different degrees of success [73]. One of these, CCX140-B [74], decreased inflammation in preclinical models of sterile peritonitis and improved glucose tolerance in obese mice [75]. A Phase I clinical trial informed for the dose chosen for ongoing Phase II trials [75].…”

“…One of these, CCX140-B [74], decreased inflammation in preclinical models of sterile peritonitis and improved glucose tolerance in obese mice [75]. A Phase I clinical trial informed for the dose chosen for ongoing Phase II trials [75].…”

The Fine Balance of Chemokines During Disease: Trafficking, Inflammation, and Homeostasis

“…It was also reported that insulin infusion can exert an anti-inflammatory effect by suppressing plasma concentrations of key chemokines involved in monocyte trafficking including CCL2 and CCL5 and their respective receptors CCR2 and CCR5 (107). Due to the importance of monocytes/macrophages in the pathology of diabetes, anti- mouse CCL2 drugs (108) and CCR2 antagonists (109) have been developed to treat T2DM diabetic nephropathy and other associated complications. The validation and applicability to T2DM patients is still uncertain.…”

Inflammation, obesity, and the promise of immunotherapy for metabolic disease

“…Human trials are in progress studying a macrophage homing molecule antagonist with early promising results (50). Targeting specific pathogenic macrophage subpopulations is another important line of research.…”