PP121 is a multi-targeted kinase inhibitor with IC₅₀s of 10, 60, 12, 14, 2 nM for mTOR, DNK-PK, VEGFR2, Src, PDGFR, respectively.

PP121 blocks the PI3K pathway by direct inhibition of PI3K/mTOR in two glioblastoma cell lines, U87 and LN229. PP121 potently inhibits the proliferation of a diverse panel of tumor cell lines containing mutations in the PI3-K pathway components PIK3CA, PTEN, or RAS. PP121 induces a G₀G₁ arrest in most tumor cells. PP121 directly inhibits Src in cells and reverses its biochemical and morphological effects. PP121 potently inhibits the Ret kinase domain in vitro (IC₅₀<1 nm). pp121 potently blocks vegf stimulated activation of the pi3-k and mapk pathways. inhibits vegfr2 autophosphorylation at low nanomolar concentrations, confirming that this molecule directly targets in cells. bcr-abl induced tyrosine phosphorylation k562 cells as well baf3 express bcr-abl^[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.

Oral administration of PP121 remarkably inhibits Eca-109 xenograft growth. Mice body weights are not significantly affected by PP121 or the vehicle treatment. PP121 oral administration dramatically inhibits activations of Akt-mTOR and NFkB in xenograft tumors. p-Akt Ser 473 and p-IKKa/b are both inhibited by PP121 administration^[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.

319.36

C₁₇H₁₇N₇

1092788-83-4

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 : 20 mg/mL (62.63 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 mg/mL (6.26 mM); Clear solution

  此方案可获得 ≥ 2 mg/mL (6.26 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 20.0 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 mg/mL (6.26 mM); Clear solution

  此方案可获得 ≥ 2 mg/mL (6.26 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 20.0 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
• 3.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2 mg/mL (6.26 mM); Clear solution

  此方案可获得 ≥ 2 mg/mL (6.26 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 20.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Apsel B, et al. Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat Chem Biol, 2008, 4(11), 691-699.

  [2]. Peng Y, et al. The anti-esophageal cancer cell activity by a novel tyrosine/phosphoinositide kinase inhibitor PP121. Biochem Biophys Res Commun. 2015 Sep 11;465(1):137-44.

Purified kinase domains are incubated with inhibitors (PP121) at 2- or 4-fold dilutions over a concentration range of 50- 0.001 µM or with vehicle (0.1% DMSO) in the presence of 10 µM ATP, 2.5 µCi of γ- ³²P-ATP and substrate. Reactions are terminated by spotting onto nitrocellulose or phosphocellulose membranes, depending on the substrate; this membrane is then washed 5-6 times to remove unbound radioactivity and dried. Transferred radioactivity is quantitated by phosphorimaging and IC₅₀ values are calculated by fitting the data to a sigmoidal doseresponse using Prism software^[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.

Cells grown in 96-well plates are treated with PP121 at 4-fold dilutions (10 µM – 0.040 μM) or vehicle (0.1% DMSO). After 72 h cells are exposed to Resazurin sodium salt (22 µM) and fluorescence is quantified. IC₅₀ values are calculated. For proliferation assays involving single cell counting, non-adherent cells are plated at low density (3–5% confluence) and treated with drug (2.5 µM) or vehicle (0.1% DMSO). Cells are diluted into trypan blue daily and viable cells counted using a hemocytometer^[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.

Mice: Eca-109 cells are injected into the axillary regions of nude mice (5×10⁶ cells/mouse). When the tumor volumes reach around 200 mm³, the mice are randomly separated to three groups: Untreated control, PP121 (30 mg/kg) and vehicle (10% 1-methyl-2-pyrrolidinone and 90% PEG 300) group. Tumor volumes and the mice body weights are measured every 10 d^[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.

• [1]. Apsel B, et al. Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat Chem Biol, 2008, 4(11), 691-699.

  [2]. Peng Y, et al. The anti-esophageal cancer cell activity by a novel tyrosine/phosphoinositide kinase inhibitor PP121. Biochem Biophys Res Commun. 2015 Sep 11;465(1):137-44.