CCR4-351 hydrochloride 是口服有效和选择性的CCR4拮抗剂。CCR4-351 hydrochloride 具有新颖的哌啶基-氮杂环丁烷基序，在钙流量和 CTX 分析中的IC50为 22 nM 和 50 nM。CCR4-351 hydrochloride 具有抗肿瘤活性。
| 生物活性 | CCR4-351 hydrochloride is an orally active, potent and selectiveCCR4antagonist. CCR4-351 hydrochloride, featuring a novel piperidinyl-azetidine motif, hasIC50s of 22 nM and 50 nM in the calcium flux and CTX assay. CCR4-351 hydrochloride has antitumor activity[1]. |
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体外研究
(In Vitro) | CCR4-351 (compound 38) hydrochloride shows no activity in a CYP450 induction assay[1].
CCR4-351 hydrochloride inhibits the migration of mouse iTregcells with an IC50of 39 nM, while the IC50in human iTregcells is 33 nM[1].
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体内研究
(In Vivo) | CCR4-351 (compound 38; 50 mg/kg; PO; daily; for 40 days) hydrochloride significantly reduces the tumor growth[1].
CCR4-351 (0.5 mg/kg; IV) hydrochloride has low clearance (CL=10.2 mL/min/kg), medium volume of distribution (Vss=5.2 L/kg), a T1/2of 6.9 h, and good bioavailability (%F = 29) of oral dosing in mouse[1].
CCR4-351 hydrochloride has low clearance (CL=7.3 mL/min/kg), a half-life of 12.7 hr, and is 44% bioavailable in dog. CCR4-351 hydrochloride has low clearance (CL=3.7 mL/min/kg), a long terminal half-life (10.7 hr), and good bioavailability (%F = 41) in cynomolgus monkey[1].
| Animal Model: | Six-to eight-week-old, female C57BL/6 mice with Pan02-OVA tumor[1] | | Dosage: | 50 mg/kg | | Administration: | PO; daily; for 40 days | | Result: | Significantly reduced the tumor growth. |
| Animal Model: | Rat and mouse[1] | | Dosage: | 0.5 mg/kg of IV; 2 mg/kg of PO | | Administration: | IV or PO | | Result: | Possessed medium clearance (CL=47.6 mL/min/kg) and was 49% bioavailable upon oral dosing in rat.
Had low clearance (CL=10.2 mL/min/kg), medium volume of distribution (Vss=5.2 L/kg), a T1/2of 6.9 h, and good bioavailability (%F = 29) of oral dosing in mouse. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | 4°C, sealed storage, away from moisture *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture) |
| 溶解性数据 | In Vitro: DMSO : 170 mg/mL(Need ultrasonic) In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 4.25 mg/mL (Infinity mM); Clear solution
此方案可获得 ≥ 4.25 mg/mL (Infinity mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 42.5 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 4.25 mg/mL (Infinity mM); Clear solution
此方案可获得 ≥ 4.25 mg/mL (Infinity mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例，取 100 μL 42.5 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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