Pyrotinib dimaleate (SHR-1258 dimaleate) is a potent and selectiveEGFR/HER2dual inhibitor withIC₅₀s of 13 and 38 nM, respectively^[1].

Pyrotinib dimaleate has high potency in HER2-dependent cell lines (BT474, SK-OV-3), while showing much weaker inhibition in the HER2 negative cell line (MDA-MB-231). Pyrotinib dimaleate inhibits BT474 and SK-OV-3 cells with IC₅₀s of 5.1 and 43 nM, respectively. Pyrotinib dimaleate displays high selectivity as HKI-272 when tested in a panel of different kinases such as KDR, c-Kit, PDGFRβ, c-Src and C-Met (c-Src with an IC₅₀of 790 nM, and others >3000 nM)^[1].

Pyrotinib dimaleate has acceptable bioavailability of 20.6%, 43.5% and 13.5% in nude mice, rats and dogs, respectively. Pyrotinib dimaleate has favorable drug-like physicochemical properties and shows relatively higher oral exposure in human subjects (oral; t_1/2=15 h) with a much longer half life than that of preclinical animal species such as mouse (i.v.; t_1/2=1.56 h; i.g.; t_1/2=2.52 h) and rat (i.v.; t_1/2=4.42 h; i.g.; t_1/2=3.38 h)^[1].

815.22

Solid

C₄₀H₃₉ClN₆O₁₁

1397922-61-0

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

H₂O : ≥ 106 mg/mL(130.03 mM)

DMSO : 100 mg/mL(122.67 mM;Need ultrasonic)

*"≥" 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℃, 6 months; -20℃, 1 month (sealed storage, away from moisture)。-80℃ 储存时，请在 6 个月内使用，-20℃ 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： 10% DMSO    40%PEG300   5%Tween-80   45% saline

  Solubility: 2.5 mg/mL (3.07 mM); Suspended solution; Need ultrasonic

  此方案可获得 2.5 mg/mL (3.07 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 25.0 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
• 2.

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

  Solubility: 2.5 mg/mL (3.07 mM); Suspended solution; Need ultrasonic

  此方案可获得 2.5 mg/mL (3.07 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 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