For research use only. Not for therapeutic Use.
<p style=/line-height:25px/>INCB3344 is a novel, potent and selective small molecule antagonist of the mouse CCR2 receptor; inhibits the binding of CCL2 to mouse monocytes with nanomolar potency (IC50 = 10 nM).<br>IC50 value: 10 nM [1]<br>Target: CCR2<br>In vitro: INCB3344 inhibits the binding of CCL2 to mouse monocytes with nanomolar potency (IC(50) = 10 nM) and displays dose-dependent inhibition of CCL2-mediated functional responses such as ERK phosphorylation and chemotaxis with similar potency. Against a panel of G protein-coupled receptors that includes other CC chemokine receptors, INCB3344 is at least 100-fold selective for CCR2 [1]. INCB3344 can also bind human CCR2 (hCCR2) with high affinity, having a dissociation constant (K(d)) of approximately 5nM. The binding of the compound to the receptor is rapid and reversible. INCB3344 potently inhibits hCCR2 binding of monocyte chemoattractant protein-1 (MCP-1) and MCP-1-induced signaling and function in hCCR2-expressing cells, including ERK phosphorylation and chemotaxis, and is competitive against MCP-1 in vitro [2].<br>in vivo: INCB3344 possesses good oral bioavailability and systemic exposure in rodents that allows in vivo pharmacological studies. INCB3344 treatment results in a dose-dependent inhibition of macrophage influx in a mouse model of delayed-type hypersensitivity [1]. Intervention with a CCR2 antagonist, INCB3344 (30 mg/kg per day, IP), 10 days after the induction of hypertension with DOCA/salt treatment, reduced the aortic expression of CCR2 mRNA and completely reversed the DOCA/salt-induced influx of macrophages [3].</p>
| Catalog Number | I001055 |
| CAS Number | 1262238-11-8 |
| Synonyms | N-[2-[[(3S,4S)-1-[4-(1,3-benzodioxol-5-yl)-4-hydroxycyclohexyl]-4-ethoxypyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide |
| Molecular Formula | C29H34F3N3O6 |
| Purity | ≥95% |
| Target | CCR2 |
| Solubility | 10 mM in DMSO |
| Storage | Store at -20°C |
| IC50 | 10 nM [1] |
| Reference | </br>1:Suppression and regression of choroidal neovascularization in mice by a novel CCR2 antagonist, INCB3344. Xie P, Kamei M, Suzuki M, Matsumura N, Nishida K, Sakimoto S, Sakaguchi H, Nishida K.PLoS One. 2011;6(12):e28933. doi: 10.1371/journal.pone.0028933. Epub 2011 Dec 19. PMID: 22205983 Free PMC Article</br>2:Discovery of INCB3344, a potent, selective and orally bioavailable antagonist of human and murine CCR2. Xue CB, Wang A, Meloni D, Zhang K, Kong L, Feng H, Glenn J, Huang T, Zhang Y, Cao G, Anand R, Zheng C, Xia M, Han Q, Robinson DJ, Storace L, Shao L, Li M, Brodmerkel CM, Covington M, Scherle P, Diamond S, Yeleswaram S, Vaddi K, Newton R, Hollis G, Friedman S, Metcalf B.Bioorg Med Chem Lett. 2010 Dec 15;20(24):7473-8. doi: 10.1016/j.bmcl.2010.10.020. Epub 2010 Oct 13. PMID: 21036044 </br>3:Pharmacological characterization of INCB3344, a small molecule antagonist of human CCR2. Shin N, Baribaud F, Wang K, Yang G, Wynn R, Covington MB, Feldman P, Gallagher KB, Leffet LM, Lo YY, Wang A, Xue CB, Newton RC, Scherle PA.Biochem Biophys Res Commun. 2009 Sep 18;387(2):251-5. doi: 10.1016/j.bbrc.2009.06.135. Epub 2009 Jul 1. PMID: 19576173 </br>4:Discovery and pharmacological characterization of a novel rodent-active CCR2 antagonist, INCB3344. Brodmerkel CM, Huber R, Covington M, Diamond S, Hall L, Collins R, Leffet L, Gallagher K, Feldman P, Collier P, Stow M, Gu X, Baribaud F, Shin N, Thomas B, Burn T, Hollis G, Yeleswaram S, Solomon K, Friedman S, Wang A, Xue CB, Newton RC, Scherle P, Vaddi K.J Immunol. 2005 Oct 15;175(8):5370-8. PMID: 16210643 Free Article |
