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Chemical Structure| 827318-97-8 Chemical Structure| 827318-97-8

Structure of Danusertib
CAS No.: 827318-97-8

Chemical Structure| 827318-97-8

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Danusertib is a pyrrolo-pyrazole and small molecule Aurora kinases inhibitor with IC50 of 13, 79, and 61 nM for Aurora A, B, and C, respectively. It is modestly potent to Abl, TrkA, c-RET and FGFR1, and less potent to Lck, VEGFR2/3, c-Kit, CDK2, etc.

Synonyms: PHA-739358

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Product Details of Danusertib

CAS No. :827318-97-8
Formula : C26H30N6O3
M.W : 474.55
SMILES Code : O=C(NC1=NNC2=C1CN(C([C@H](OC)C3=CC=CC=C3)=O)C2)C4=CC=C(N5CCN(C)CC5)C=C4
Synonyms :
PHA-739358
MDL No. :MFCD12024692
InChI Key :XKFTZKGMDDZMJI-HSZRJFAPSA-N
Pubchem ID :11442891

Safety of Danusertib

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of Danusertib

epigenetics
DNA
RTK

Isoform Comparison

Biological Activity

Target
  • Aurora A

    Aurora A, IC50:13 nM

  • Aurora B

    Aurora B, IC50:79 nM

  • Aurora C

    Aurora C, IC50:61 nM

  • FGFR1

    FGFR1, IC50:47 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
MCF7 cells 100 nM 2-3 weeks To evaluate the inhibitory effect of Danusertib on MCF7 cells in the bone microenvironment, results showed that Danusertib significantly inhibited the proliferation of MCF7 cells. PMC6239211
MDA-MB-361 cells 100 nM 2-3 weeks To evaluate the inhibitory effect of Danusertib on MDA-MB-361 cells in the bone microenvironment, results showed that Danusertib significantly inhibited the proliferation of MDA-MB-361 cells. PMC6239211
Ba/F3 BCR-ABLT315I cells 300 nM 6 hours Evaluate the effect of Danusertib on the transcriptome of BCR-ABLT315I cells, showing no significantly regulated genes when used alone. PMC4038039
Ba/F3 BCR-ABLT315I cells 300 nM Danusertib + 1 μM Bosutinib 6 hours Evaluate the effect of Danusertib and Bosutinib combination on the transcriptome of BCR-ABLT315I cells, showing 645 genes significantly upregulated and 584 genes significantly downregulated. PMC4038039
K562-S cells 1 μM 24 hours To evaluate the effect of Danusertib on apoptosis in K562-S cells, results showed a significant increase in apoptosis. PMC6533706
K562-R cells 1 μM 24 hours To evaluate the effect of Danusertib on apoptosis in K562-R cells, results showed a significant increase in apoptosis. PMC6533706
Huh-7 50 nM 96 hours inhibition of tumor cell proliferation PMC2735802
HepG2 50 nM 96 hours inhibition of tumor cell proliferation PMC2735802

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice 4T1.2 spontaneous bone metastasis model Intraperitoneal injection 20 mg/kg once daily for three 7-day cycles To evaluate the inhibitory effect of Danusertib on spontaneous bone metastasis of 4T1.2 cells, results showed that Danusertib significantly reduced the occurrence of bone metastasis. PMC6239211
Mice Chronic doxorubicin-induced cardiomyopathy model Intraperitoneal injection 1 mg/mouse every other day for 16 days Danusertib inhibited DUSP5 siRNA+T3-induced cardiomyocyte proliferation, preventing increases in LV mass, posterior wall thickness, ejection fraction, and fractional shortening, indicating that cardiomyocyte proliferation underlies the improvement in LV function and structure induced by DUSP5 siRNA+T3 therapy. PMC7978295
NOD/SCID mice HCC xenograft model intraperitoneal injection 15 mg/kg Daily until the end of the experiment significantly inhibited tumor growth PMC2735802

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT00335868 Leukemia Phase 2 Unknown - United States, California ... More >> Jonsson Comprehensive Cancer Center at UCLA Los Angeles, California, United States, 90095-1781 Less <<
NCT00766324 Metastatic Hormone Refractory ... More >>Prostate Cancer Less << Phase 2 Completed - Italy ... More >> Nerviano Medical Sciences. Clinical Research Dept. Nerviano, Milano, Italy, 20014 Less <<
NCT00872300 Multiple Myeloma PHASE2 TERMINATED 2025-09-10 MAYO Clinic, Scottsdale, Arizo... More >>na, 85259, United States|The Robert H Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois, 60611, United States|H?pital Huriez, Centre Hospitalier Régional Universitaire de Lille, Lille, 59037, France|University Hospital H?tel-Dieu, Nantes, 44093, France Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.11mL

0.42mL

0.21mL

10.54mL

2.11mL

1.05mL

21.07mL

4.21mL

2.11mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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