Home Cell Cycle Aurora Kinase inhibitor - Bcr-Abl inhibitor - c-RET inhibitor - FGFR inhibitor - Autophagy activator - Apoptosis related activator - Trk receptor inhibitor Danusertib (PHA-739358) For research use only.

Danusertib (PHA-739358)

Danusertib (PHA-739358) is an Aurora kinase inhibitor for Aurora A/B/C with IC50 of 13 nM/79 nM/61 nM in cell-free assays, modestly potent to Abl, TrkA, c-RET and FGFR1, and less potent to Lck, VEGFR2/3, c-Kit, CDK2, etc. Danusertib induces apoptosis, cell cycle arrest, and autophagy. Phase 2.

Danusertib (PHA-739358) Chemical Structure

Danusertib (PHA-739358) Chemical Structure

CAS No. 827318-97-8

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Danusertib (PHA-739358) Related Products

Signaling Pathway

Aurora Kinase Signaling Pathways

Aurora Kinase Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
A2780 cells Proliferation assay Antiproliferative activity against A2780 cells, IC50=28 nM 17125279
HCT116 cells Proliferation assay Antiproliferative activity against HCT116 cells, IC50=31 nM 17125279
human HCT116 cells Proliferation assay Antiproliferative activity against human HCT116 cells assessed as BrdU incorporation after 72 hrs, IC50=31 nM 19320489
HCT116 cells Function assay Cell cycle arrest in HCT116 cells by accumulation at G2/M phase, EC50=80 nM 17125279
MCF7 cells Proliferation assay Antiproliferative activity against MCF7 cells, IC50=80 nM 17125279
HeLa cells Proliferation assay Antiproliferative activity against HeLa cells, IC50=0.14 μM 17125279
human MOLT4 cells Cytotoxic assay Cytotoxicity against human MOLT4 cells assessed as inhibition of cell growth after 4 days by Cell Titer Blue end-point assay, EC50=0.15 μM 22889561
human HepG2 cells Cytotoxic assay Cytotoxicity against human HepG2 cells after 48 hrs by MTT assay, TC50=4 μM 24910766
human A2780 cells Proliferation assay Antiproliferative activity against human A2780 cells assessed as accumulation of 4N DNA, IC50=28 μM 19320489
HCT116 cells Function assay Inhibition of histone h3 phosphorylation in HCT116 cells by Western blot analysis 17125279
Click to View More Cell Line Experimental Data

Biological Activity

Description Danusertib (PHA-739358) is an Aurora kinase inhibitor for Aurora A/B/C with IC50 of 13 nM/79 nM/61 nM in cell-free assays, modestly potent to Abl, TrkA, c-RET and FGFR1, and less potent to Lck, VEGFR2/3, c-Kit, CDK2, etc. Danusertib induces apoptosis, cell cycle arrest, and autophagy. Phase 2.
Targets
Aurora A [1]
(Cell-free assay)		 Abl [1]
(Cell-free assay)		 RET [1]
(Cell-free assay)		 TrkA [1]
(Cell-free assay)		 FGFR1 [1]
(Cell-free assay)		 Click to View More Targets
13 nM 25 nM 31 nM 31 nM 47 nM
In vitro
In vitro Danusertib inhibits the activities of other kinases such as FGFR1, Abl, Ret and Trka, with IC50 of 47 nM, 25 nM, 31 nM and 31 nM, respectively. In a cell assay, after treatment of wild-type and p53-deficient MEFs with Danusertib, the wild-type cells undergo an arrest in mitosis (4N) that is maintained for up to 48 h. The p53-deficient cells on the other hand do not arrest at the 4N DNA stage, but continues with additional rounds of DNA synthesis to become >8N. Treatment with Danusertib results in an increase in p53 protein levels and an associated increase in p21 protein, which is known to be transcriptionally regulated by p53. [1] Increasing concentrations of Danusertib produces a dose-dependent reduction of cell growth after 48 hours in BCR-ABL-positive (K562, BV173) and BCR-ABL-negative (HL60) cells. [3]
Kinase Assay Biochemical kinase Assays
The Km values for ATP and the specific substrate are initially determined, and each assay is then run at optimized ATP (2Km) and substrate (5Km) concentrations. This setting enabled direct comparison of IC50 values of Danusertib across the applied kinase selectivity screening panel for the evaluation of the selectivity profile.
Cell Research Cell lines CD34+ cells
Concentrations 5 μM
Incubation Time 5 days
Method For short-term expansion assays, 1 × 103 CD34+ cells are plated in triplicates in 96-well plates containing 100 μL of serum-free medium per well supplemented with human stem-cell factor (100 ng/mL), human Flt-3 Ligand (100 ng/mL), human thrombopoietin (50 ng/mL), human interleukin-3 and -6 (IL-3 and IL-6, respectively, both 20 ng/mL), and granulocyte colony-stimulating factor (20 ng/mL) along with Danusertib at the indicated concentrations. After 5 days, an additional 100 μL of cytokine and Danusertib containing medium are added. Cell numbers within each individual well are estimated on days 3, 6, and 9 or on days 3, 6, and 12 for healthy donor samples.
In Vivo
In vivo Administration of 25 mg/kg Danusertib (b.d. i.v.) to HL-60 xenograft rats results in 75% inhibition of tumor growth with complete regression in one animal. Danusertib results in biomarker modulation accompanied by inhibition of tumor growth. This is compatible with an expected mechanism of action of aurora kinase inhibition. [1] Danusertib significantly inhibits proliferation of K562 cells and virtually suppressed tumor growth during the 10-day treatment period. [3]
Animal Research Animal Models Female SCID mice
Dosages 15 mg/kg
Administration Intraperitoneally

Chemical Information & Solubility

Molecular Weight 474.55 Formula

C26H30N6O3
CAS No. 827318-97-8 SDF Download Danusertib (PHA-739358) SDF
Smiles CN1CCN(CC1)C2=CC=C(C=C2)C(=O)NC3=NNC4=C3CN(C4)C(=O)C(C5=CC=CC=C5)OC
Storage (From the date of receipt)

In vitro
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DMSO : 95 mg/mL ( (200.18 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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