| 產(chǎn)品描述： | INCB3344 is a potent, selective and orally bioavailable CCR2 antagonist with IC50 values of 5.1 nM (hCCR2) and 9.5 nM (mCCR2) in binding antagonism and 3.8 nM (hCCR2) and 7.8 nM (mCCR2) in antagonism of chemotaxis activity. |
| 靶點(diǎn)： |
hCCR2:5.1 nM (IC50);mCCR2:9.5 nM (IC50);CCR |
| 體內(nèi)研究： |
When administered intravenously to CD-1 mice, INCB3344 exhibits a high clearance and a moderate volume of distribution, resulting in a short half life of 1 h. Despite its high clearance, however, good oral exposure is achieved, with an AUC at 2664 nM h at a dose of 10 mg/kg. The oral bioavailability is 47%. By comparison, slightly better oral exposure (AUC=3888 nM h) is obtained when administered orally to Balb/c mice at the same dose. This PK property, couple with its potent anti-mCCR2 activity and good selectivity, makes this compound suitable for model studies in rodents. INCB3344 prevents Deoxycorticosterone acetate/salt-induced changes in vascular expression of CCR2. In a separate series of experiments, CCR2 expression is elevated (≈1.5-fold higher) in aortas from mice that receive INCB3344 from days 7 to 21 of the Deoxycorticosterone acetate/salt treatment period compare with sham animals; however, this level of CCR2 expression is significantly lower than that observed in the vehicle-treated group (P<0.05, n=6). Likewise, increased expression of its receptor ligand CCL2 in Deoxycorticosterone acetate/salt-treated mice is blunted in mice receiving INCB3344 (P<0.05, n=6). By contrast, levels of CCL7, CCL8, and CCL12 are elevated to similar extents in Deoxycorticosterone acetate/salt-treated mice receiving vehicle or INCB3344 |
| 參考文獻(xiàn)： |
1. Xue CB, et al. Discovery of INCB3344, a potent, selective and orally bioavailable antagonist of human and murine CCR2. Bioorg Med Chem Lett. 2010 Dec 15;20(24):7473-8 2. Brodmerkel CM, et al. Discovery and pharmacological characterization of a novel rodent-active CCR2 antagonist, INCB3344. J Immunol. 2005 Oct 15;175(8):5370-8. 3. Chan CT, et al. Reversal of vascular macrophage accumulation and hypertension by a CCR2 antagonist in deoxycorticosterone/salt-treated mice. Hypertension. 2012 Nov;60(5):1207-12. 4. Dansereau MA, et al. Spinal CCL2 pronociceptive action is no longer effective in CCR2 receptor antagonist-treated rats. J Neurochem. 2008 Jul;106(2):757-69. 5. Zhao W, et al. Enrichment of Ly6Chi monocytes by multiple GM-CSF injections with HBV vaccine contributes to viral clearance in a HBV mouse model. Hum Vaccin Immunother. 2017 Dec 2;13(12):2872-2882. 6. Aye-Mon A, et al. CCR2 upregulation in DRG neurons plays a crucial role in gastric hyperalgesia associated with diabetic gastropathy. Mol Pain. 2018 Jan-Dec;14:1744806917751322. 7. Cassini MF, et al. Mcp1 Promotes Macrophage-Dependent Cyst Expansion in Autosomal Dominant Polycystic Kidney Disease. J Am Soc Nephrol. 2018 Oct;29(10):2471-2481. |
| 溶解性： |
DMSO : 220 mg/mL (380.89 mM; Need ultrasonic) |
| 保存條件： |
-20℃ |
| 配置溶液濃度參考： |
|
1mg |
5mg |
10mg |
| 1 mM |
1.732 ml |
8.662 ml |
17.324 ml |
| 5 mM |
0.346 ml |
1.732 ml |
3.465 ml |
| 10 mM |
0.173 ml |
0.866 ml |
1.732 ml |
| 50 mM |
0.035 ml |
0.173 ml |
0.346 ml |
|
| 注意： |
部分產(chǎn)品我司僅能提供部分信息，我司不保證所提供信息的權(quán)威性，僅供客戶參考交流研究之用。 |
上海工商
危險(xiǎn)品化學(xué)品經(jīng)營(yíng)許可證（不帶存儲(chǔ)）
營(yíng)業(yè)執(zhí)照(三證合一)
北京