PKI-402 is a selective, reversible, ATP-competitive inhibitor of PI3K, including PI3K-α mutants, and mTOR (IC₅₀=2, 3, 7,14 and 16 nM for PI3Kα, mTOR, PI3Kβ, PI3Kδ and PI3Kγ).

PKI-402 is an equipotent inhibitor of class I PI3K, including the E545K and H1047R PI3K-α mutants (IC₅₀=2, 3 and 3 nM for PI3Kα, PI3Kα-H1047R and PI3Kα-E545K, respectively). PKI-402 causes in vitro growth inhibition of human tumor cell lines derived from a diverse set of human tumor tissues, including breast, brain (glioma), pancreas, and non-small cell lung cancer (NSCLC) tissues. PKI-402 inhibits MDA-MB-361 [breast: Her2⁺ and PIK3CA mutant (E545K)], with an IC₅₀ of 6 nM. PKI-402 inhibits HCT116 (K-Ras and PIK3CA mutant) with an IC₅₀ of 33 nM^[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.

PKI-402 displays antitumor activity (i.v. route) in breast [MDA-MB-361: Her2⁺ and PIK3CA (E545K)], glioma (U87MG and PTEN), and NSCLC (A549; K-Ras and STK11) xenograft models. PKI-402 causes regression in the MDA-MB-361 xenograft model. PKI-402 effect is most pronounced at 100 mg/kg (daily for 5 days, one round), which reduces initial tumor volume and prevents tumor re-growth for 70 days. In MDA-MB-361 tumor tissue, PKI-402 at 100 mg/kg (single dose) fully suppresses p-Akt at both the T308 and the S473 sites at 8 hours and induces cleaved PARP. At 24 hours, p-Akt suppression is still evident, as is cleaved PARP^[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.

570.65

C₂₉H₃₄N₁₀O₃

1173204-81-3

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 : 5 mg/mL (8.76 mM; Need ultrasonic)

H₂O : < 0.1 mg/mL (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。-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。

• [1]. Mallon R et al. Antitumor efficacy profile of PKI-402, a dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor. Mol Cancer Ther. 2010 Apr;9(4):976-84.

Enzyme assays are done in fluorescent polarization (FP) format. Human class I PI3Ks and PI3K-α mutants (E545K and H1047R) are produced in Sf9. GST-GRP1 (murine) is produced in Escherichia coli and isolated by GST-Sepharose. Assay buffers are reaction buffer [20 mM HEPES (pH 7.1), 2 mM MgCl₂, 0.05% CHAPS, and 0.01% β-mercaptoethanol] and stop/detection buffer [100 mM HEPES (pH 7.5), 4 mM EDTA, 0.05% CHAPS]. FP reaction is run for 30 min at room temperature in 20 μL of reaction buffer containing 20 μM phosphatidylinositol 4,5-bisphosphate (PIP2), 25 μM ATP, and <4% DMSO (compound solvent). FP reaction is stopped with 20 μL of stop/detection buffer (10 nM probe and 40 nM GST-GRP), and after 2 h, data are collected. Selectivity of PKI-402 is evaluated in the 236 human kinase panel at [ATP]=K_m for each enzyme^[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.

MDA-MB-361, MDA-MB-468, T47D, MCF7, BT474, HT29, HCT116, DLD1, U87MG, H157, NCI-H460, A549, NCI-H1975, NCI-H1650, NCI-H2170, KB, 786-0, A498, MIA-PaCa-2, and PC3 cell lines are propagated at 37°C in 5% CO₂ incubators in supplier-recommended growth medium. Cell growth inhibition is determined using the CellTiter 96 AQueous proliferation assay. Data are collected after 72 h using a Wallac Victor2 V 1420 multilabel HTS counter. FOXO-GFP translocation in U2OS cells is quantified after 60-min PKI-402 exposure using a Cellomics ArrayScan VTI Reader^[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^[1]
PKI-402 or vehicle is administered by i.v. route. Nude mice bearing MDA-MB-361 tumors are used. Tumor weight is calculated. Pharmacodynamic (biomarker) measurements are done on tumor-bearing female nude mice administered PKI-402. Tumor or normal tissue samples are collected from euthanized animals, homogenized, washed twice with cold (4°C) PBS, and then treated with cell lysis buffer^[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.

• [1]. Mallon R et al. Antitumor efficacy profile of PKI-402, a dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor. Mol Cancer Ther. 2010 Apr;9(4):976-84.