Samotolisib (LY3023414) potently and selectively inhibitsclass IPI3Kisoforms,DNA-PK, andmTORC1/2withIC₅₀s of 6.07 nM, 77.6 nM, 38 nM, 23.8 nM, 4.24 nM and 165 nM forPI3Kα,PI3Kβ,PI3Kδ,PI3Kγ,DNA-PKandmTOR, respectively. Samotolisib potently inhibitsmTORC1/2at low nanomolar concentrations^[1][2].

In cell-based assays, Samotolisib (LY3023414) inhibition of PI3K and mTOR is assessed in the PTEN-deficient U87 MG glioblastoma cell line. Samotolisib inhibits the phosphorylation of Akt at position T308 downstream of PI3K at an IC₅₀of 106 nM. Similarly, Samotolisib inhibits phosphorylation of Akt at position S473 (IC₅₀=94.2 nM) by mTORC2 as well as phosphorylation of mTORC1 kinase targets p70S6K (position T389; IC₅₀=10.6 nM) and 4E-BP1 (positions T37/46; IC₅₀=187 nM). The downstream phosphorylation of S6RP at positions pS240/244 (IC₅₀=19.1 nM) by p70S6K is inhibited as well, indicating target inhibition along the entire PI3K/Akt/mTOR pathway by Samotolisib. Similar IC₅₀concentrations for PI3K and mTOR phosphorylation targets are observed in other cell lines with activated PI3K/Akt/mTOR pathways. The ability of Samotolisib to inhibit cancer cell proliferation is evaluated in 32 human cancer cell lines from different tumor types in culture after Samotolisib treatment for 2 to 3 cell doublings in dose–response studies. Samotolisib demonstrates potent single-agent activity and IC₅₀values below 122 nM in half of the cell lines tested^[1].

The ability of Samotolisib (LY3023414) to inhibit tumor growth is studied in several xenograft models exhibiting mutations or deletions that activate the PI3K/Akt/mTOR pathway. Treatment with Samotolisib at 3, 6, or 10 mg/kg twice daily orally for 28 days results in dose-responsive inhibition of tumor growth in the PTEN-deleted U87 MG xenograft model. This treatment produces similar TGI in models exhibiting PTEN truncation (786-O), activating PI3Kα mutation (NCI-H1975), and transgenic Eμ-myc mutant PI3Kα-driven leukemia models. Of note, the total daily dose of Samotolisib appears to result in equipotent antitumor activity: 12 mg/kg once daily and 6 mg/kg twice daily produces similar delta T/C values (42% and 38%, respectively) in U87 MG^[1].

406.48

Solid

C₂₃H₂₆N₄O₃

1386874-06-1

Room temperature in continental US; may vary elsewhere.

DMSO : 50 mg/mL(123.01 mM;Need ultrasonic)

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• 1.

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

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  此方案可获得 ≥ 2.5 mg/mL (6.15 mM，饱和度未知) 的澄清溶液。

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• 2.

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  此方案可获得 ≥ 2.5 mg/mL (6.15 mM，饱和度未知) 的澄清溶液。

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• 3.

  请依序添加每种溶剂： 10% DMSO    90%corn oil

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  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玉米油中，混合均匀。

• 4.

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• 5.

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• 6.

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