Ravoxertinib hydrochloride (GDC-0994 hydrochloride) is an orally bioavailable inhibitor selective for ERK kinase activity with IC₅₀ of 6.1 nM and 3.1 nM for ERK1 and ERK2, respectively.

Ravoxertinib also inhibits p90RSK with IC₅₀ of 12 nM^[1].
Ravoxertinib is highly selective for ERK1 and ERK2, with biochemical potency of 1.1 nM and 0.3 nM, respectively^[2].
Ravoxertinib (GDC0994; 50 nM, 0.5 µM, and 5 µM; 48 hours) decreases the viability of lung adenocarcinoma cell lines (A549, HCC827, HCC4006)^[4].

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.

In CD-1 mice, a 10 mg/kg oral dose of Ravoxertinib is sufficient to achieve the desired target coverage for at least 8 h^[1]. Daily, oral dosing of Ravoxertinib results in significant single-agent activity in multiple in vivo cancer models, including KRAS-mutant and BRAF-mutant human xenograft tumors in mice^[2].

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.

477.32

C₂₁H₁₉Cl₂FN₆O₂

2070009-58-2

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)

DMSO : 100 mg/mL (209.50 mM; Need ultrasonic)

H₂O : < 0.1 mg/mL (ultrasonic;warming;heat to 80°C) (insoluble)

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 (sealed storage, away from moisture)。-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： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.5 mg/mL (5.24 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.24 mM，饱和度未知) 的澄清溶液。

  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-CD in saline)

  Solubility: ≥ 2.5 mg/mL (5.24 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.24 mM，饱和度未知) 的澄清溶液。

  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 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

• [1]. Blake JF, et al. Discovery of (S)-1-(1-(4-Chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (GDC-0994), an Extracellular Signal-Regulated Kinase 1/2 (ERK1/2) Inhibitor in Early Clinical Developme

  [2]. Kirk Robarge, et al. Abstract DDT02-03: Discovery of GDC-0994, a potent and selective ERK1/2 inhibitor in early clinical development. Proceedings: AACR Annual Meeting 2014; April 5-9, 2014.

  [3]. MICHAEL LAI. Opportunity for Pharmaceutical Intervention in Lung Cancer: Selective Inhibition of JAK1/2 to Eliminate EMT-Derived Mesenchymal Cells.

Mice^[1]
PK/PD data for Ravoxertinib in the HCT116 mouse xenograft model. HCT116 tumors are established in nude mice to a tumor volume of 400−600 mm³. Mice are treated with a single oral dose of 22 at 15, 30, or 100 mg/kg versus vehicle control alone (40% PEG400/60% (10% HPβCD)) follow by tumor and plasma collection at 2, 8, 16, and 24 h postdose. Tumor levels of phosphorylated p90RSK (pRSK) relative total p90RSK (tRSK) are measured by quantitative Western blot and are normalized to vehicle control at 2 h postdose (set to 100%). Plasma and tumor concentrations are measured by LC−MS.

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]. Blake JF, et al. Discovery of (S)-1-(1-(4-Chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (GDC-0994), an Extracellular Signal-Regulated Kinase 1/2 (ERK1/2) Inhibitor in Early Clinical Developme

  [2]. Kirk Robarge, et al. Abstract DDT02-03: Discovery of GDC-0994, a potent and selective ERK1/2 inhibitor in early clinical development. Proceedings: AACR Annual Meeting 2014; April 5-9, 2014.

  [3]. MICHAEL LAI. Opportunity for Pharmaceutical Intervention in Lung Cancer: Selective Inhibition of JAK1/2 to Eliminate EMT-Derived Mesenchymal Cells.