ACT-660602 是一种具有口服活性的趋化因子受体CXCR3拮抗剂，IC50为 204 nM。ACT-660602 抑制 T 细胞迁移，并在体内急性肺损伤模型中表现出显著作用。ACT-660602 可用于自身免疫性疾病的研究。
| 生物活性 | ACT-660602 is an orally active antagonist ofchemokine receptor(CXCR3) with anIC50value of 204 nM. ACT-660602 inhibits T-cell migration and shows efficacy in acute lung ingury model. ACT-660602 can be used for autoimmune diseases research[1][2]. |
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体外研究
(In Vitro) | ACT-660602 shows selectivity to CXCR3 over hERG, with IC50s of 18 μM (hERG)[1].
ACT-660602 (112 nM; 6 h) inhibits cell migration and improves the metabolic stability[1].
ACT-660602 (5, 20, 100 or 500 nM) displays an non-competitive binding mode to CXCL10 and CXCL11 in different concentration, with more stable IC50s[1].
Cell Migration Assay[1] | Cell Line: | CD3/CD28-activated primary human T cells | | Concentration: | 112 nM | | Incubation Time: | 45 min | | Result: | Inhibited cell migration. |
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体内研究
(In Vivo) | ACT-660602 (1 μM; 6 h) intrinsic metabolic clearance (CLint) in human, rat, mouse liver microsomes (HLM, RLM, MLM)[1].
ACT-660602 (30 mg/kg; p.o.; once daily) displays anti-inflammatory activity and exerts efficacy in the mouse model of acute lung ingury[1].
Range for Pharmacokinetics of ACT-660602[1]
| Animal | Route | Dose (range) (mg/kg) | Cmax(range) (ng/mL) | Tmax(range) (h) | AUC (range) (ngoh/mL) | F (%) | CL (range) (mL/min/kg) | Vss(range) (L/kg) | T1/2(range) (h) | | Dog | p.o. | 2 | 1380 | 1 | 20000 | 8 | 1.3 | 1.7 | 14.5 | | i.v. | 0.5 | 1300-1450 | 0.5-2.0 | 10400-32000 | / | 0.6-3.0 | 1.6-1.7 | 6.3- | | Rat | p.o. | 2 | 1520 | 0.5 | 14000 | 80 | 1.9 | 1.1 | 7.1 | | i.v. | 0.5 | 1250-1860 | 0.5-1.0 | 11600-15641 | / | 1.9-1.9 | 0.9-1.3 | 5.7-8.8 |
| Animal Model: | LPS-induced lung inflammation model (72 h post LPS challenge)[1] | | Dosage: | 30 mg/kg | | Administration: | Oral gavage; once daily | | Result: | Significantly reduced recruitment of the CXCR3+ CD8+ T cell in the bronchoalveolar lavage compartment. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
| 溶解性数据 | In Vitro: DMSO : 110 mg/mL(205.81 mM;Need ultrasonic) 配制储备液 | 1 mM | 1.8710 mL | 9.3549 mL | 18.7098 mL | | 5 mM | 0.3742 mL | 1.8710 mL | 3.7420 mL | | 10 mM | 0.1871 mL | 0.9355 mL | 1.8710 mL |
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