2. PI3K/Akt/mTOR Cell Cycle/DNA Damage Autophagy
  3. PI3K DNA-PK mTOR Autophagy
  4. Samotolisib

Samotolisib  (Synonyms: LY3023414)

Cat. No.: HY-12513 Purity: 99.42%
COA Handling Instructions

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Samotolisib (LY3023414) potently and selectively inhibits class I PI3K isoforms, DNA-PK, and mTORC1/2 with IC50s of 6.07 nM, 77.6 nM, 38 nM, 23.8 nM, 4.24 nM and 165 nM for PI3Kα, PI3Kβ, PI3Kδ, PI3Kγ, DNA-PK and mTOR, respectively. Samotolisib potently inhibits mTORC1/2 at low nanomolar concentrations.

For research use only. We do not sell to patients.

Samotolisib Chemical Structure

Samotolisib Chemical Structure

CAS No. : 1386874-06-1

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Solid + Solvent
10 mM * 1 mL in DMSO
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Based on 4 publication(s) in Google Scholar

Samotolisib Related Antibodies

Top Publications Citing Use of Products

View All PI3K Isoform Specific Products:

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PI3Kα PI3Kβ PI3Kγ PI3Kδ PI3KC2α PI3KC2β PI3KC2γ Vps34 PI3K PI3KC3 p120γ

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mTOR mTORC1 mTORC2

  • Biological Activity

  • Protocol

  • Purity & Documentation

  • References

  • Customer Review

Description

Samotolisib (LY3023414) potently and selectively inhibits class I PI3K isoforms, DNA-PK, and mTORC1/2 with IC50s of 6.07 nM, 77.6 nM, 38 nM, 23.8 nM, 4.24 nM and 165 nM for PI3Kα, PI3Kβ, PI3Kδ, PI3Kγ, DNA-PK and mTOR, respectively. Samotolisib potently inhibits mTORC1/2 at low nanomolar concentrations[1][2].

IC50 & Target[2]

PI3Kα

6.07 nM (IC50)

PI3Kγ

23.8 nM (IC50)

PI3Kδ

38 nM (IC50)

PI3Kβ

77.6 nM (IC50)

DNA-PK

4.24 nM (IC50)

mTOR

165 nM (IC50)

mTORC1

 

mTORC2

 

In Vitro

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 IC50 of 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 IC50 concentrations 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 IC50 values below 122 nM in half of the cell lines tested[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Samotolisib Related Antibodies
In Vivo

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
Molecular Weight

406.48

Formula

C23H26N4O3
CAS No.
Appearance

Solid

Color

Light yellow to yellow

SMILES

O=C(N1C[C@@H](OC)C)N(C)C2=C1C3=CC(C4=CC(C(C)(O)C)=CN=C4)=CC=C3N=C2
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 2 years
-20°C 1 year
Solvent & Solubility
In Vitro: 

DMSO : 50 mg/mL (123.01 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.4601 mL 12.3007 mL 24.6015 mL
5 mM 0.4920 mL 2.4601 mL 4.9203 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

  • Molarity Calculator

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Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass
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Concentration
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Volume
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Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

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Volume (start)

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C2

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In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 2.5 mg/mL (6.15 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

    Solubility: ≥ 2.5 mg/mL (6.15 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

    Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
% 
+
%
Tween-80 +
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation

Purity: 99.42%

COA (250 KB) LCMS (267 KB)

Handling Instructions (2659 KB)
References
Cell Assay
[1]

The CellTiter-Glo luminescent cell viability assay system is used to measure the antiproliferative effects of Samotolisib after 2 cell doublings on cells plated on plastic or incubated for 2 weeks in soft agar with a collection of standard cell lines and human patient–derived tumor xenografts passaged in nude mice. For the soft-agar assay, RKO and SK-OV-3 cells; MOLT-4 and L-363 cells; DLD-1, HCT-116, HCT-15, and NCI-H460 cells are used. These standard cell lines are genotyped by STR and matched to existing STR reference genotypes. Oncotest PDX models (including model MX1 originally derived at NCI) are characterized using the Affymetrix genome-wide human SNP Array 6.0 as well as whole-exome sequencing. Genetic identity analysis confirm that all PDX models are derived from independent patient samples. Combination studies are conducted in which Samotolisib is mixed with other therapeutic agents in fixed ratios of concentrations corresponding to the IC50 equivalents of each single agent. The combination index at 50% inhibition (CI50) is calculated[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration
[1]

Mice[1]
Xenograft tumors are implanted subcutaneously in athymic nude, CD-1 nude mice, and NMRI athymic nude mice. B6.Cg-Tg(IghMyc)22Bri/J mice and C57BL/6NTac mice are used in the Eμ-myc transgenic orthotopic mutant PI3Kα E545K-driven leukemia model similar to the Akt1 E17K cancer model. Samotolisib is formulated in 1% HEC in distilled water containing 0.25% polysorbate 80 and 0.05% Dow-Corning Antifoam 1510-US and administered by oral gavage (final volume 0.2 mL) at the indicated doses and schedules. Efficacy and in vivo target inhibition studies are carried out after tumor volumes reach 150 to 200 mm3. Target inhibition studies are conducted at various time points after administration of a single dose of Samotolisib to mice harboring tumors. Tumors are harvested, flash frozen, lysed in MSD buffer, and then analyzed using the MSD-ELISA multiplex method.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 2.4601 mL 12.3007 mL 24.6015 mL 61.5036 mL
5 mM 0.4920 mL 2.4601 mL 4.9203 mL 12.3007 mL
10 mM 0.2460 mL 1.2301 mL 2.4601 mL 6.1504 mL
15 mM 0.1640 mL 0.8200 mL 1.6401 mL 4.1002 mL
20 mM 0.1230 mL 0.6150 mL 1.2301 mL 3.0752 mL
25 mM 0.0984 mL 0.4920 mL 0.9841 mL 2.4601 mL
30 mM 0.0820 mL 0.4100 mL 0.8200 mL 2.0501 mL
40 mM 0.0615 mL 0.3075 mL 0.6150 mL 1.5376 mL
50 mM 0.0492 mL 0.2460 mL 0.4920 mL 1.2301 mL
60 mM 0.0410 mL 0.2050 mL 0.4100 mL 1.0251 mL
80 mM 0.0308 mL 0.1538 mL 0.3075 mL 0.7688 mL
100 mM 0.0246 mL 0.1230 mL 0.2460 mL 0.6150 mL
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Samotolisib Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

Samotolisib1386874-06-1LY3023414LY 3023414LY-3023414PI3KDNA-PKmTORAutophagyPhosphoinositide 3-kinaseDNA-dependent protein kinaseMammalian target of RapamycinInhibitorinhibitorinhibit

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