Danusertib (PHA-739358)

Catalog No.S1107

Danusertib (PHA-739358) Chemical Structure

Molecular Weight(MW): 474.55

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. Phase 2.

Size Price Stock Quantity  
In DMSO USD 238 In stock
USD 170 In stock
USD 320 In stock
USD 970 In stock
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4 Customer Reviews

  • Mice bearing subcutaneous allografts of conditional patched mutant tumor cells were treated twice weekly with vehicle (saline) or 30 mg/kg PHA-739358. (B)Images of tumors. (C) Tumor weights. Each point represents a single tumor, and grey lines represent mean tumor weights, which were significantly different between vehicle and PHA-739358 treated mice (p < 0.05, based on paired two-tailed t-test).

    Cancer Res 2013 73(20), 6310-22. Danusertib (PHA-739358) purchased from Selleck.

    For MTT assays, cells (2,000 ~ 5,000 cells/well) were subcultured into 96-well plates according to their growth properties. Cell proliferation was assayed at 72 hr after treatment of PHA-739358 by adding 20 μl of 5 mg/ml 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) solution per 100 μl of growth medium. After incubating for 3-4 h at 37°C, the media were removed and 150 µl/well of MTT solvent (either absolute DMSO or isopropanol containing 4 mM HCl and 0.1% Nonidet-40) was added to dissolve the formazan. The absorbance of each well was measured by ELx808 (BioTek, Winooski, VT) or Wallac Victor2 (Perkin-Elmer Life Sciences, Boston, MA) Microplate Reader. Viable cells are presented as percent of control, vehicle-treated cells.

    Dr. Yong-Weon Yi from Georgetown University Medical Center. Danusertib (PHA-739358) purchased from Selleck.

  • AsPC-1 cells were treated with PHA-739358 (PHA) (3 uM), imatinib (15 uM), or combination of PHA and imatinib for 72 hours and Bcl2 and Bcl-xL expression levels by Western blotting.

    Biochem Pharmacol 2012 83(4), 452-61. Danusertib (PHA-739358) purchased from Selleck.

    Western blot analysis of Histone and Aurora kinase. 0-10μM PHA739358 was added.

    Dr. Zhang of Tianjin Medical University. Danusertib (PHA-739358) purchased from Selleck.

Purity & Quality Control

Choose Selective Aurora Kinase Inhibitors

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. 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)
13 nM 25 nM 31 nM 31 nM 47 nM
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]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
A2780 cells M1HCcXBzd2yrZnXyZZRqd25iYYPzZZk> NHTaWlFCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JGEzPzhyIHPlcIx{NCCLQ{WwQVI5KG6P NXK3cYFxOTdzMkWyO|k>
HCT116 cells M{XDbnBzd2yrZnXyZZRqd25iYYPzZZk> M1PLcWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgTGNVOTF4IHPlcIx{NCCLQ{WwQVMyKG6P M{XGU|E4OTJ3Mke5
human HCT116 cells M2rIfHBzd2yrZnXyZZRqd25iYYPzZZk> NEHVeVBCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFjDWFEyPiClZXzsd{Bie3Onc4Pl[EBieyCEcnTVJIlv[2:{cH;yZZRqd25iYX\0[ZIhPzJiaILzMEBKSzVyPUOxJI5O M1WzXlE6OzJyNEi5
HCT116 cells NGfxXGNHfW6ldHnvckBie3OjeR?= MVjD[YxtKGO7Y3zlJIFzemW|dDDpckBJS1RzMU[gZ4VtdHNiYomgZYNkfW23bHH0bY9vKGG2IFeyM20heGijc3WsJGVEPTB;OECgcm0> MXmxO|EzPTJ5OR?=
MCF7 cells NUTCXFQ4WHKxbHnm[ZJifGmxbjDhd5NigQ>? MVrBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IF3DSlch[2WubIOsJGlEPTB;OECgcm0> M1zRXVE4OTJ3Mke5
HeLa cells NIPmN2FRem:uaX\ldoF1cW:wIHHzd4F6 MUnBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IFjlUIEh[2WubIOsJGlEPTB;MD6xOEDPxE1? MlXNNVcyOjV{N{m=
human MOLT4 cells NVfRdYJYS3m2b4TvfIlkyqCjc4PhfS=> M4rTRWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJG1QVFR2IHPlcIx{KGG|c3Xzd4VlKGG|IHnubIljcXSrb36gc4Yh[2WubDDndo94fGhiYX\0[ZIhPCCmYYnzJIJ6KEOnbHygWIl1\XJiQnz1[UBmdmRvcH;pcpQh[XO|YYmsJGVEPTB;MD6xOUDPxE1? NHT3WlkzOjh6OUW2NS=>
human HepG2 cells NI\6SItEgXSxdH;4bYPDqGG|c3H5 NIq3VIVEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBJ\XCJMjDj[YxteyCjZoTldkA1QCCqcoOgZpkhVVSWIHHzd4F6NCCWQ{WwQVQh|ryP NG\1[VEzPDlzMEe2Oi=>
human A2780 cells Mof0VJJwdGmoZYLheIlwdiCjc4PhfS=> NVz0R296SW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDBNlc5OCClZXzsd{Bie3Onc4Pl[EBieyCjY3P1cZVt[XSrb36gc4YhPE5iRF7BMEBKSzVyPUK4JO69VQ>? Mn;MNVk{OjB2OEm=
HCT116 cells M1\1VGZ2dmO2aX;uJIF{e2G7 NUn2[oNKUW6qaXLpeIlwdiCxZjDobZN1d26nIHizJJBpd3OyaH;yfYxifGmxbjDpckBJS1RzMU[gZ4VtdHNiYomgW4V{fGW{bjDicI91KGGwYXz5d4l{ M{O5OlE4OTJ3Mke5

... Click to View More Cell Line Experimental Data

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]

Protocol

Kinase Assay:[1]
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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:[3]
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  • 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.
    (Only for Reference)
Animal Research:[3]
+ Expand
  • Animal Models: Female SCID mice
  • Formulation: In DMSO
  • Dosages: 15 mg/kg
  • Administration: Intraperitoneally
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 95 mg/mL (200.18 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents individually and in order:
1% DMSO+30% polyethylene glycol+1% Tween 80
30 mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 474.55
Formula

C26H30N6O3

CAS No. 827318-97-8
Storage powder
Synonyms N/A

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00872300 Terminated Multiple Myeloma Nerviano Medical Sciences October 2008 Phase 2
NCT00766324 Completed Metastatic Hormone Refractory Prostate Cancer Nerviano Medical Sciences September 2007 Phase 2
NCT00335868 Unknown status Leukemia Jonsson Comprehensive Cancer Center|National Cancer Institute (NCI) March 2007 Phase 2

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.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID