ACP-5862 is a major active, circulating, pyrrolidine ring-opened metabolite of Acalabrutinib with an IC₅₀ of 5.0 nM for Bruton tyrosine kinase (BTK). ACP‐5862 is a weak time‐dependent inactivator of CYP3A4 and CYP2C8. Acalabrutinib is an orally active, irreversible, and highly selective BTK inhibitor, with an IC₅₀ of 3 nM and EC₅₀ of 8 nM^[1][2].

Following a single oral dose of 100 mg Acalabrutinib, the half‐life of ACP‐5862 is 6.9 hours and the mean exposure is approximately twofold to threefold higher than that of Acalabrutinib^[2].
ACP-5862 (M27) is the major single metabolite in the systemic circulation and accountes for 57.4% and 42.1% of the AUC_0-t total radioactivity in male and female rat plasma, respectively. ACP-5862, the major human metabolite, is a relatively minor component in the systemic circulation and accountes for 6.1% and 8.1% of the AUC_0-t total radioactivity in male and female dog plasma, respectively^[1].
ACP-5862 (1 or 10 μM) has reversible protein binding of 98.6%, 99.8%, 94.3%, 98.6% in mouse, rat, dog, and human plasma^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

481.51

C₂₆H₂₃N₇O₃

2230757-47-6

Room temperature in continental US; may vary elsewhere.

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

In Vitro: 

DMSO : 250 mg/mL (519.20 mM; Need ultrasonic)

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

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: ≥ 2.08 mg/mL (4.32 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (4.32 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 20.8 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。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• [1]. Herman SE, et al. The Bruton’s tyrosine kinase (BTK) inhibitor acalabrutinib demonstrates potent on-target effects and efficacy in two mouse models of chronic lymphocytic leukemia. Clin Cancer Res. 2016 Nov 30

  [2]. Diansong Zhou, et al. Evaluation of the Drug-Drug Interaction Potential of Acalabrutinib and Its Active Metabolite, ACP-5862, Using a Physiologically-Based Pharmacokinetic Modeling Approach. CPT Pharmacometrics Syst Pharmacol. 2019 Jul;8(7):489-499.