| Description | Cenicriviroc (TAK-652) is an orally active, dual antagonist of CCR2/CCR5. It also inhibits both HIV-1 and HIV-2, and displays potent anti-infective and anti-inflammatory activity. |
| In vitro | Cenicriviroc 阻止 HIV-1 的细胞进入[2]。就测试的 4 个 R5 HIV-2 临床分离株而言，cenicriviroc 的有效浓度 50% (EC50) 分别为 0.03、0.33、0.45 和 0.98 nM。具有双重亲和性和 X4-亲和性的 HIV-2 株对 cenicriviroc 显示出抗性，其 EC50 值均 >1000 nM，MPI 分别为 33% 和 4% [3]。 |
| In vivo | Cenicriviroc (≥20 mg/kg/天) 在体内显著减少单核细胞/巨噬细胞的招募。在NASH模型中，cenicriviroc 显著降低非酒精性脂肪肝病活动评分。Cenicriviroc治疗对体重或肝/肾重量没有显著影响[1]。 |
| Animal experiments | Male C57BL/6 mice (n=44; 8-10 weeks of age) are allocated to receive treatments via oral gavage (PO) on Days 1-5 in the following groups: non-disease control, vehicle control twice daily (BID), Cenicriviroc 5 mg/kg/day (Cenicriviroc5) BID, Cenicriviroc 20 mg/kg/day (Cenicriviroc20) BID, Cenicriviroc 100 mg/kg/day (Cenicriviroc100) BID, Cenicriviroc20 QD, and positive control (corticosteroid known to reduce inflammation in a variety of animal models) 1 mg/kg QD. On Day 4, peritonitis is induced via IP injection of TG 3.85% (1 mL/animal) 2 hours post-dose in all groups except non-disease controls [1]. |
| Target activity | CCR5:0.29 nM, CCR2:5.9 nM, R5 HIV-1:0.024-0.08 nM (in PBMCs), R5 HIV-2:0.03-0.98 nM (in PBMCs) |
| Synonyms | TAK-652, TBR-652 |
| molecular weight | 696.94 |
| Molecular formula | C41H52N4O4S |
| CAS | 497223-25-3 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 120 mg/mL (172.19 mM) |
| References | 1. Lefebvre E, et al. Antifibrotic Effects of the Dual CCR2/CCR5 Antagonist Cenicriviroc in Animal Models of Liver and Kidney Fibrosis. PLoS One. 2016 Jun 27;11(6):e0158156 2. Kuwata T, et al. Incompatible Natures of the HIV-1 Envelope in Resistance to the CCR5 Antagonist Cenicriviroc and to Neutralizing Antibodies. Antimicrob Agents Chemother. 2015 Nov 2;60(1):437-5 3. Visseaux B, et al. Cenicriviroc, a Novel CCR5 (R5) and CCR2 Antagonist, Shows In Vitro Activity against R5 Tropic HIV-2 Clinical Isolates. PLoS One. 2015 Aug 6;10(8):e0134904 |