| Bioactivity | Avacopan (CCX168) is a potent, selective and orally available complement 5a receptor (C5aR) inhibitor with an IC50 of 0.1 nM. | ||||||||||||
| Target | IC50: 0.1 nM (complement 5a receptor ) | ||||||||||||
| Invitro | CCX168 取代[125I]-C5a 与人骨髓细胞系 (U937) 上的 C5aR 结合，效力 (IC50) 为 0.1 nM。CCX168 抑制 C5a 介导的 U937 细胞趋化性，效力 (CCX168 的浓度在 C5a 活性中产生 2 倍右移) 为 0.2 nM。CCX168 竞争性和选择性地阻断纯化的人嗜中性粒细胞中 C5a 诱导的钙动员，IC50 值为 0.2 nM。CCX168 抑制 C5a 诱导的分离的中性粒细胞释放活性氧，并能够完全阻断这些中性粒细胞的呼吸爆发[1]。 MCE has not independently confirmed the accuracy of these methods. They are for reference only. 0 --> Avacopan 相关抗体: | ||||||||||||
| In Vivo | CCX168 显示在广泛的剂量范围 (1 至 100 毫克) 内具有良好的耐受性，并且显示出剂量依赖性药代动力学。每天两次口服 30 mg CCX168 可在一整天内阻断循环中性粒细胞中 C5a 诱导的 CD11b 上调 94% 或更多，表明基本完全覆盖靶标。在口服 0.03 mg/kg CCX168 的小鼠中，所得血浆 CCX168 浓度为 15 nM (8.7 ng/mL)，可将循环白细胞的下降从 53% 降低至 25%。在给予 0.3 mg/kg CCX168 的小鼠中，75 nM (44 ng/mL) 的血浆 CCX168 浓度使循环白细胞相对于基线的下降从 53% 减少到 10% (与对照相比，p<0.05)。 在 hC5aR 敲入小鼠中，口服剂量为 3 或 30 mg/kg 的 CCX168 可完全阻断 C5a 诱导的白细胞减少症[1]。口服 CCX168，每天 30 mg/kg，可降低 hC5aR 小鼠中抗 MPO NCGN 的严重程度。CCX168 组肾小球月牙状病变由 30.4% 降至 3.3%。每天接受 CCX168 30 mg/kg 的小鼠的尿血尿、蛋白尿和白细胞尿减少。CCX168 的保护导致新月体和坏死减少[2]。 MCE has not independently confirmed the accuracy of these methods. They are for reference only. | ||||||||||||
| CAS | 1346623-17-3 | ||||||||||||
| Formula | C33H35F4N3O2 | ||||||||||||
| Molar Mass | 581.64 | ||||||||||||
| Appearance | 固体 | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
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| Reference | [1]. Bekker P, et al. Characterization of Pharmacologic and Pharmacokinetic Properties of CCX168, a Potent and Selective Orally Administered Complement 5a Receptor Inhibitor, Based on Preclinical Evaluation and Randomized Phase 1 Clinical Study. PLoS One. 2016 Oct 21;11(10):e0164646. [2]. Xiao H, et al. C5a receptor (CD88) blockade protects against MPO-ANCA GN. J Am Soc Nephrol. 2014 Feb;25(2):225-31. |
Avacopan
CAS: 1346623-17-3 F: C33H35F4N3O2 W: 581.64
Avacopan (CCX168) is a potent, selective and orally available complement 5a receptor (C5aR) inhibitor with an IC50 of 0.
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