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Chemical Structure| 639089-54-6 Chemical Structure| 639089-54-6

Structure of Tozasertib
CAS No.: 639089-54-6

Chemical Structure| 639089-54-6

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Tozasertib is the inhibitor of Aurora-A, -B, -C kinases with Ki values of 0.6, 18, 4.6 nM respectively.

Synonyms: VX 680; MK-0457; VE465

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Product Details of Tozasertib

CAS No. :639089-54-6
Formula : C23H28N8OS
M.W : 464.59
SMILES Code : O=C(C1CC1)NC2=CC=C(SC3=NC(N4CCN(C)CC4)=CC(NC5=NNC(C)=C5)=N3)C=C2
Synonyms :
VX 680; MK-0457; VE465
MDL No. :MFCD13185152
InChI Key :GCIKSSRWRFVXBI-UHFFFAOYSA-N
Pubchem ID :5494449

Safety of Tozasertib

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Related Pathways of Tozasertib

epigenetics
DNA

Isoform Comparison

Biological Activity

Target
  • Aurora A

    Aurora A, Ki app:0.6 nM

  • Aurora B

    Aurora B, Ki app:18 nM

  • Aurora C

    Aurora C, Ki app:4.6 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
GFP-AZI2 -4OHT cells 5 µM 24 h Screen for compounds that induce AZI2 puncta formation PMC10936636
HCT-116 cells 10 μM 24 h or 48 h To assess the effect of Tozasertib on DNA content in HCT-116 cells, results showed that Tozasertib treatment led to polyploidy. PMC5508574
MDA-MB-468 breast cancer cells 1-10 μM 2 h To evaluate the inhibitory effect of Tozasertib on Aurora A Thr288 autophosphorylation, results showed effective inhibition of Aurora A activity at concentrations ranging from 1-10 μM. PMC4429609
SKHep1 liver cancer cells 0.2 µM 7 days Induced cellular senescence, followed by treatment with Ouabain, Digoxin, or ABT-263, effectively killing senescent cancer cells. PMC6887543
A549 lung cancer cells 0.2 µM 7 days Induced cellular senescence, followed by treatment with Ouabain, Digoxin, or ABT-263, effectively killing senescent cancer cells. PMC6887543
HCT-116 cells 10 μM 24 h or 48 h To evaluate the effect of Tozasertib on DNA content in HCT-116 cells PMC5508574
Jurkat T cells 10 μM 24 h To assess the effect of Tozasertib on cytokine release from T cells, results showed that Tozasertib significantly upregulated the transcriptional expression of TNF-α, IFN-γ, and GZMB. PMC10828585
B16F10 cells 10 μM 24 h To analyze the effect of Tozasertib on the transcriptome of B16F10 cells, results showed that Tozasertib significantly affected cell cycle-related pathways and immune response pathways. PMC10828585
H23 cells 10 μM 24 h Tozasertib inhibited AURKA and increased the expression of GLI-1 and KRAS PMC10789740
H358 cells 10 μM 24 h Tozasertib inhibited AURKA and increased the expression of GLI-1 and KRAS PMC10789740
SKHep1 cells 0.2 μM 7 days Induced senescence in SKHep1 cells PMC6887543
A549 cells 0.2 μM 7 days Induced senescence in A549 cells PMC6887543
Patched mutant tumor cells 0.15 nM - 1.5 µM 48 hours To evaluate the inhibitory effect of CCT129202 on tumor cell proliferation, results showed significant inhibition of tumor cell proliferation. PMC3800039

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
C57BL/6 mice B16F10 melanoma xenograft model Intraperitoneal injection 50 mg/kg Once daily for 7 days To evaluate the anti-tumor immune effects of Tozasertib in a melanoma xenograft model, results showed that Tozasertib significantly suppressed tumor growth and reduced the number of Treg cells in the tumors. PMC10828585

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT00500006 Chronic Myelogenous Leukemia ... More >> Leukemia, Lymphoblastic, Acute, Philadelphia-Positive Less << Phase 1 Terminated - -
NCT00405054 Leukemia Phase 2 Terminated - -
NCT00290550 Carcinoma, Non-Small-Cell Lung Phase 2 Terminated - -
NCT00099346 Colorectal Cancer ... More >> Advanced Solid Tumors Less << Phase 1 Terminated - -
NCT00111683 Chronic Myelogenous Leukemia i... More >>n Blast Crisis Lymphocytic Leukemia, B Cell, Acute Myelodysplastic Syndromes Myelogenous Leukemia, Chronic Less << Phase 1 Completed - -
NCT02532868 Cancer PHASE1 TERMINATED 2025-01-08 -

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.15mL

0.43mL

0.22mL

10.76mL

2.15mL

1.08mL

21.52mL

4.30mL

2.15mL

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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