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抑制剂/激活剂

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凋亡与自噬

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INCB3344

INCB3344 是一种有效的 CCR2 拮抗剂，拮抗结合活性时，IC50 为 5.1 nM (hCCR2) 和 9.5 nM (mCCR2)，拮抗趋化活性时，IC50 为 3.8 nM (hCCR2) 和 7.8 nM (mCCR2)。

货号：
TK0595
规格：

1mg

5mg

10mg
价格：
￥0.00

产品参数

CAS No.	1262238-11-8
生物活性	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.
分子式	C29H34N3O6F3
分子量	577.59
运输条件	Room temperature in continental US; may vary elsewhere.
储存条件	Powder -20°C 3 years
溶解性数据	DMSO : 220 mg/mL (380.89 mM; Need ultrasonic)
体内研究	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.
体外研究	INCB3344 is a potent antagonist towards rat and cynomolgus CCR2 as well, displaying IC50 values of 7.3 and 16 nM in binding antagonism and 2.7 and 6.2 nM in antagonism of chemotaxis activity, respectively. INCB3344 is a selective hCCR2 antagonist, exhibiting IC50 values of more than 1 μM against a panel of >50 ion channels, transporters, chemokine receptors and other selected GPCRs. It is also a selective mCCR2 antagonist, showing IC50 values of >1 μM and >3 μM against murine CCR1 and murine CCR5, respectively, the two most homologous chemokine receptors to mCCR2. Characterization of the pharmacological activity of INCB3344 is first evaluated by testing its ability to inhibit CCL2 binding to CCR2 in a whole cell binding assay using a murine monocyte cell line, WEHI-274.1 and I-labeled mCCL2 as a tracer. The binding IC50 of INCB3344 in this assay is determined to be 10±5 nM, and inhibition of >90% binding is observed at a concentration of 90 nM.
文献	•EMBO Mol Med. 2015 Mar 14;7(5):547-61. •Hypertension. 2012 Nov;60(5):1207-12. •J Am Soc Nephrol. 2018 Oct;29(10):2471-2481. •Diabetes. 2019 Nov;68(11):2063-2073. •EMBO Rep. 2016 Dec;17(12):1738-1752. •J Neuroinflammation. 2021 Sep 12;18(1):196. •Acta Neuropathol Commun. 2014 Aug 23;2(1):98. •J Neurosci. 2015 Jan 7;35(1):4-20. •J Biol Chem. 2018 Jun 22;293(25):9685-9695. •Inflammopharmacology. 2018 Feb;26(1):207-215. •Neuroscience. 2020 Jan 15;425:29-38. •Mol Pain. 2018 Jan-Dec;14:1744806917751322. •Hum Vaccin Immunother. 2017 Dec 2;13(12):2872-2882. •Oncotarget. 2018 Jul 13;9(76):34213-34228. •Department of Physiology. University of Toronto. 2016 Nov.
纯度及产品资料	98%

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