Danusertib (PHA-739358)


Danusertib (PHA-739358)化学構造


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.

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  • c, Upper panel: viable cell number of FLT3-ITD-positive AML patient samples incubated with vandetanib, danusertib, or DMSO for 7 days in methylcellulose. The mean ± SD of duplicates is shown. Lower panel: viability and proliferation of mutant FLT3-positive AML cell lines and one AML patient sample treated with vandetanib and crenolanib alone or in combination for 3 days. The calculated additive effects of both inhibitors according to the Bliss Independence model are indicated by the dashed lines. The mean ± SD of four (cell lines) or two (patient sample) independent experiments is shown. P-values were calculated using one-way ANOVA followed by Dunnett’s test for multiple comparisons. *P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001.

    Leukemia, 2018, doi: 10.1038/s41375-018-0102-4. Danusertib (PHA-739358) purchased from Selleck.

    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.


Aurora Kinase阻害剤の選択性比較


製品説明 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.
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

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 Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
A2780 cells NFXSPZhRem:uaX\ldoF1cW:wIHHzd4F6 NH;mVWlCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JGEzPzhyIHPlcIx{NCCLQ{WwQVI5KG6P MWWxO|EzPTJ5OR?=
HCT116 cells NFPuVFhRem:uaX\ldoF1cW:wIHHzd4F6 MlzoRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDIR3QyOTZiY3XscJMtKEmFNUC9N|Ehdk1? NF7oPIwyPzF{NUK3PS=>
human HCT116 cells Mke1VJJwdGmoZYLheIlwdiCjc4PhfS=> MVjBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEiFVEGxOkBk\WyuczDhd5Nme3OnZDDhd{BDemSXIHnuZ49zeG:{YYTpc44h[W[2ZYKgO|IhcHK|LDDJR|UxRTNzIH7N NFyyeW0yQTN{MES4PS=>
MCF7 cells M3LxcXBzd2yrZnXyZZRqd25iYYPzZZk> NHLaTYRCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JG1ETjdiY3XscJMtKEmFNUC9PFAhdk1? NUnUPGxQOTdzMkWyO|k>
HeLa cells MV3Qdo9tcW[ncnH0bY9vKGG|c3H5 MVvBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IFjlUIEh[2WubIOsJGlEPTB;MD6xOEDPxE1? MV:xO|EzPTJ5OR?=
human MOLT4 cells M{HuemN6fG:2b4jpZ:Kh[XO|YYm= MXrDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDNU2xVPCClZXzsd{Bie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJINmdGxiZ4Lve5RpKGGodHXyJFQh\GG7czDifUBE\WyuIGTpeIVzKEKudXWg[Y5lNXCxaX70JIF{e2G7LDDFR|UxRTBwMUWg{txO NU\jVZdrOjJ6OEm1OlE>
human HepG2 cells NVvnXYJFS3m2b4TvfIlkyqCjc4PhfS=> MVnDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDI[ZBIOiClZXzsd{Bi\nSncjC0PEBpenNiYomgUXRVKGG|c3H5MEBVSzVyPUSg{txO M{HNc|I1QTFyN{[2
human A2780 cells NVPlc3VwWHKxbHnm[ZJifGmxbjDhd5NigQ>? MmPjRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCDMke4NEBk\WyuczDhd5Nme3OnZDDhd{Bi[2O3bYXsZZRqd25ib3[gOG4hTE6DLDDJR|UxRTJ6IN88US=> NUnKPJhuOTl|MkC0PFk>
HCT116 cells NF;pOYVHfW6ldHnvckBie3OjeR?= MojOTY5pcWKrdHnvckBw\iCqaYP0c45mKGh|IIDoc5NxcG:{eXzheIlwdiCrbjDIR3QyOTZiY3XscJMh[nliV3XzeIVzdiCkbH;0JIFv[Wy7c3nz MVexO|EzPTJ5OR?=


体内試験 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]


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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.
細胞試験: [3]
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  • 細胞株: CD34+ cells
  • 濃度: 5 μM
  • 反応時間: 5 days
  • 実験の流れ: 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.
+ 展開
  • 動物モデル: Female SCID mice
  • 製剤: In DMSO
  • 投薬量: 15 mg/kg
  • 投与方法: Intraperitoneally

溶解度 (25°C)

体外 DMSO 95 mg/mL (200.18 mM)
Water Insoluble
Ethanol Insoluble
体内 左から(NMPから)右の順に溶剤を製品に加えます(文献ではなく、Selleckの実験によるデータ):
1% DMSO+30% polyethylene glycol+1% Tween 80
30 mg/mL

* 溶解度測定はSelleck技術部門によって行われており、その他文献に示されている溶解度と差異がある可能性がありますが、同一ロットの生産工程で起きる正常な現象ですからご安心ください。


分子量 474.55


CAS No. 827318-97-8
in solvent
別名 N/A





質量 (g) = 濃度 (mol/L) x 体積 (L) x 分子量 (g/mol)


  • 質量





開始濃度 x 開始体積 = 最終濃度 x 最終体積


この方程式は、一般に略語を使われます:C1V1 = C2V2 ( 入力 出力 )

  • C1



  • 連続希釈剤

  • 計算結果

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):




チップス: 化学式は大文字と小文字の区別ができます。C10H16N2O2 c10h16n2o2


質量 濃度 体積 分子量


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



Handling Instructions


  • * 必須

Aurora Kinaseシグナル伝達経路

Aurora Kinase Inhibitors with Unique Features

相関Aurora Kinase製品

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細胞株 試験類型 濃度 培養時間 溶剤類型 活性叙述 PMID