1. Cell Cycle/DNA Damage Epigenetics Autophagy
  2. Aurora Kinase Autophagy
  3. Danusertib

Danusertib  (Synonyms: PHA-739358)

Cat. No.: HY-10179 Purity: 99.44%
COA Handling Instructions

Danusertib is a pyrrolo-pyrazole and aurora kinase inhibitor with IC50 of 13, 79, and 61 nM for Aurora A, B, and C, respectively.

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

Danusertib Chemical Structure

Danusertib Chemical Structure

CAS No. : 827318-97-8

Size Price Stock Quantity
Solid + Solvent
10 mM * 1 mL in DMSO
ready for reconstitution
USD 151 In-stock
Solution
10 mM * 1 mL in DMSO USD 151 In-stock
Solid
1 mg USD 69 In-stock
5 mg USD 145 In-stock
10 mg USD 251 In-stock
50 mg USD 779 In-stock
100 mg USD 1122 In-stock
200 mg   Get quote  
500 mg   Get quote  

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This product is a controlled substance and not for sale in your territory.

Customer Review

Based on 5 publication(s) in Google Scholar

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  • Biological Activity

  • Protocol

  • Purity & Documentation

  • References

  • Customer Review

Description

Danusertib is a pyrrolo-pyrazole and aurora kinase inhibitor with IC50 of 13, 79, and 61 nM for Aurora A, B, and C, respectively.

IC50 & Target[1]

Aurora A

13 nM (IC50)

Aurora B

79 nM (IC50)

Aurora C

61 nM (IC50)

In Vitro

Danusertib (0.01 to 50 μM) significantly decreases viability of C13 and A2780cp cells. The IC50s are 10.40 and 1.83 μM for C13 cells, and 19.89 and 3.88 μM for A2780cp cells after 24- and 48-h treatment. Danusertib induces cell cycle arrest in G2/M phase in C13 and A2780cp cells. Danusertib treatment results in a marked increase in the percentage of cells arrested in G2/M phase and an accumulation of polyploidy in C13 and A2780cp cells. Danusertib demotes the expression of CDK1/CDC2 and cyclin B1 but promotes the expression of p21 Waf1/Cip1, p27 Kip1, and p53. Danusertib induces autophagy in C13 and A2780cp cells with the involvement of PI3K/Akt/mTOR signaling pathway[1]. PHA-739358 strongly inhibits proliferation of all leukemic cell lines tested, with IC50 values ranging from 0.05 μM to 3.06 μM. PHA-739358 induces antiproliferative effects in BaF3-p210 cells, including IM-resistant M351T, E255K, and T315I mutants. PHA-739358 (5 μM) reduces phosphorylation of CrkL in BaF3-p210 wt cells and IM-resistant mutants[2]. Danusertibsertib leads to cell-cycle arrest and completely inhibits cell proliferation of the GEP-NET cells in vitro[3].

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

In Vivo

PHA-739358 (15 mg/kg twice a day, i.p.) and IM are well tolerated, and significantly inhibit proliferation of K562 cells andvirtually suppressed tumor growth during the 10-day treatment period[2]. In a subcutaneous murine xenograft model, danusertibsertib (2×15 mg/kg/d, i.p.) significantly reduces tumor growth in vivo compared with controls or mice treated with streptozotocine/5-fluorouracil[3].

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

Clinical Trial
Molecular Weight

474.55

Formula

C26H30N6O3

CAS No.
Appearance

Solid

Color

Off-white to yellow

SMILES

O=C(N1CC2=C(NN=C2NC(C3=CC=C(N4CCN(CC4)C)C=C3)=O)C1)[C@@H](C5=CC=CC=C5)OC

Shipping

Room temperature in continental US; may vary elsewhere.

Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 1 year
-20°C 6 months
Solvent & Solubility
In Vitro: 

DMSO : 50 mg/mL (105.36 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 2.1073 mL 10.5363 mL 21.0726 mL
5 mM 0.4215 mL 2.1073 mL 4.2145 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, 1 years; -20°C, 6 months. When stored at -80°C, please use it within 1 years. When stored at -20°C, please use it within 6 months.

  • Molarity Calculator

  • Dilution Calculator

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

Mass
=
Concentration
×
Volume
×
Molecular Weight *

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

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

×
Volume (start)

V1

=
Concentration (final)

C2

×
Volume (final)

V2

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: ≥ 2.08 mg/mL (4.38 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 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: ≥ 2.08 mg/mL (4.38 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 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: 99.44%

References
Cell Assay
[1]

The MTT assay is performed to examine the effect of danusertib on the viability of C13 and A2780cp cells. Briefly, cells are seeded in 96-well culture plates at a density of 8×l03 cells/well. After cells are attached, the cells are treated with danusertib at different concentrations (0.01-50 μM). The control cells receive the vehicle only. After 24-h incubation, 10 μL MTT (5 g/L) is added to each well and cultured for another 4 h. Then, the media is carefully aspirated and 100 μL DMSO is added. The absorbance at the 450 nm wavelength is measured with a Synergy H4 Hybrid microplate reader. The IC50 values are determined using the relative viability over danusertib concentration curve using GraphPad Prism 6.0.

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

Animal Administration
[2]

To evaluate the efficacy and toxicity of PHA-739358 in vivo, a subcutaneous animal model for CML is used; 5×107 K562 cells are injected into the flanks of female SCID mice and tumor growth is monitored daily by palpation. On day 7, when tumors reach an estimated weight of 100 to 150 mg, animals are assigned to 3 experimental groups by random selection and receive the following treatment for a period of 10 days: group 1, control, vehicle solution (7 mice); group 2, PHA-739358 twice a day intraperitoneally at a dose of 15 mg/kg (7 mice); and group 3, IM twice a day per os at 100 mg/kg. Tumor growth is assessed by caliper, and tumor weight is calculated according to the following formula: Tumor weight=[length (mm) × width2 (mm)]/2. Toxicity is monitored by changes in body weight and vitality of the animals.

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, 1 years; -20°C, 6 months. When stored at -80°C, please use it within 1 years. When stored at -20°C, please use it within 6 months.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 2.1073 mL 10.5363 mL 21.0726 mL 52.6815 mL
5 mM 0.4215 mL 2.1073 mL 4.2145 mL 10.5363 mL
10 mM 0.2107 mL 1.0536 mL 2.1073 mL 5.2681 mL
15 mM 0.1405 mL 0.7024 mL 1.4048 mL 3.5121 mL
20 mM 0.1054 mL 0.5268 mL 1.0536 mL 2.6341 mL
25 mM 0.0843 mL 0.4215 mL 0.8429 mL 2.1073 mL
30 mM 0.0702 mL 0.3512 mL 0.7024 mL 1.7560 mL
40 mM 0.0527 mL 0.2634 mL 0.5268 mL 1.3170 mL
50 mM 0.0421 mL 0.2107 mL 0.4215 mL 1.0536 mL
60 mM 0.0351 mL 0.1756 mL 0.3512 mL 0.8780 mL
80 mM 0.0263 mL 0.1317 mL 0.2634 mL 0.6585 mL
100 mM 0.0211 mL 0.1054 mL 0.2107 mL 0.5268 mL
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  • Do most proteins show cross-species activity?

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