Arginase inhibitor 1 is a potent inhibitor of human arginases I and II with IC₅₀s of 223 and 509 nM, respectively.

IC50: 223 nM (arginases I), 509 nM (arginases II)^[1]

Arginase inhibitor 1inhibits human arginases I and II with IC₅₀s of 223±22.3 and 509±85.1 nM, respectively, and is active in a recombinant cellular assay overexpressing human arginase I (CHO cells). Arginase inhibitor 1 is a novel second generation arginase inhibitor with significant activity in a rat model of myocardial ischemia/reperfusion injury (MI/RI). Arginase inhibitor 1 is potent against hARG I in both in vitro enzyme and cellular assays. The IC₅₀ for Arginase inhibitor 1 is 8 μM in CHO Cells Over-Expressing hArgI^[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.

A pharmacokinetic evaluation of Arginase inhibitor 1 is conducted after intravenous (i.v.) and oral (p.o.) dosing in male Sprague-Dawley rats (n=3 per dose route). Arginase inhibitor 1 is formulated in 0.9% saline and administered intravenously at 10 mg/kg by bolus through a preimplanted cannula at a dosing volume of 1 mL/kg, and orally at 10 mg/kg via gavage at a dosing volume of 2 mL/kg. Following i.v. dosing with 10 mg/kg in fasted animals, Arginase inhibitor 1has a terminal elimination half-life (t_1/2) of 3.3 h with a volume of distribution and total body clearance of 1.86 L/kg and 7.89 mL/min/kg, respectively. The oral bioavailability of Arginase inhibitor 1 (10 mg/kg, p.o.) is 28% with a C_max of 0.45 mg/L^[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.

286.18

C₁₃H₂₇BN₂O₄

1345808-25-4

Room temperature in continental US; may vary elsewhere.

DMSO : ≥ 48 mg/mL (167.73 mM)

H₂O : ≥ 30 mg/mL (104.83 mM)

* “≥” means soluble, but saturation unknown.

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。

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： PBS

  Solubility: 65 mg/mL (227.13 mM); Clear solution; Need ultrasonic
• 2.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 1.67 mg/mL (5.84 mM); Clear solution

  此方案可获得 ≥ 1.67 mg/mL (5.84 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 16.7 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

• 3.

  请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

  Solubility: ≥ 1.67 mg/mL (5.84 mM); Clear solution

  此方案可获得 ≥ 1.67 mg/mL (5.84 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 16.7 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 4.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 1.67 mg/mL (5.84 mM); Clear solution

  此方案可获得 ≥ 1.67 mg/mL (5.84 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 16.7 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Van Zandt MC, et al. Discovery of (R)-2-amino-6-borono-2-(2-(piperidin-1-yl)ethyl)hexanoic acid and congeners as highly potentinhibitors of human arginases I and II for treatment of myocardial reperfusion injury. J Med Chem. 2013 Mar 28;56(6):2568-80.

Rats^[1]
Single dose pharmacokinetics are evaluated in male Sprague-Dawley rats by intravenous bolus (i.v.) and oral (p.o.) dosing. Three rats are evaluated per dose group. Arginase inhibitor 1 is freshly formulated in 0.9% saline prior to dosing, at 10 mg/mL for i.v. dosing at a dose volume of 1 mL/kg animal body weight, and at 5 mg/mL for p.o. dosing at a dose volume of 2 mL/kg. Animals are fasted overnight prior to dosing, with water given ad libitum. Arginase inhibitor 1 is administered i.v. through a preimplanted cannula or orally by gavage. Food is reintroduced to animals 4 h following dosing. Blood samples are collected through preimplanted cannulae (dual cannulated animals used for i.v. dosing; blood collection separate from dosing cannula) at 0.25 mL per draw, followed by volume replacement with 0.9% saline. Samples are collected at predose 0.083 (i.v. only), 0.25, 0.5, 1, 2, 4, 6, 8, and 24 h following dosing. Blood samples are maintained on ice and centrifuged at 10 000g to obtain plasma. Plasma is frozen at -20 °C prior to analysis. Analysis is performed by LC/MS/MS. Pharmacokinetic evaluation is performed using standard noncompartmental analyses in Phoenix WinNonlin software.

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.

• [1]. Van Zandt MC, et al. Discovery of (R)-2-amino-6-borono-2-(2-(piperidin-1-yl)ethyl)hexanoic acid and congeners as highly potentinhibitors of human arginases I and II for treatment of myocardial reperfusion injury. J Med Chem. 2013 Mar 28;56(6):2568-80.