Danusertib (PHA-739358)

Catalog No.S1107

For research use only.

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

CAS No. 827318-97-8

Selleck's Danusertib (PHA-739358) has been cited by 32 publications

Purity & Quality Control

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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

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 M1LiUXBzd2yrZnXyZZRqd25iYYPzZZk> NVzYc|NMSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBCOjd6MDDj[YxteyxiSVO1NF0zQCCwTR?= M4P4cVE4OTJ3Mke5
HCT116 cells MVPQdo9tcW[ncnH0bY9vKGG|c3H5 NGr0ZXJCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JGhEXDFzNjDj[YxteyxiSVO1NF0{OSCwTR?= MXuxO|EzPTJ5OR?=
human HCT116 cells NUT1OWkzWHKxbHnm[ZJifGmxbjDhd5NigQ>? NGXHdHhCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFjDWFEyPiClZXzsd{Bie3Onc4Pl[EBieyCEcnTVJIlv[2:{cH;yZZRqd25iYX\0[ZIhPzJiaILzMEBKSzVyPUOxJI5O NF\nZ3EyQTN{MES4PS=>
HCT116 cells M13XN2Z2dmO2aX;uJIF{e2G7 MnjBR4VtdCCleXPs[UBienKnc4SgbY4hUEOWMUG2JINmdGy|IHL5JIFk[3WvdXzheIlwdiCjdDDHNk9OKHCqYYPlMEBGSzVyPUiwJI5O MWKxO|EzPTJ5OR?=
MCF7 cells NWHaTWJsWHKxbHnm[ZJifGmxbjDhd5NigQ>? MVzBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IF3DSlch[2WubIOsJGlEPTB;OECgcm0> MXyxO|EzPTJ5OR?=
HeLa cells MnXvVJJwdGmoZYLheIlwdiCjc4PhfS=> MnvsRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDI[WxiKGOnbHzzMEBKSzVyPUCuNVQh|ryP M2n5OlE4OTJ3Mke5
human MOLT4 cells MYfDfZRwfG:6aXRCpIF{e2G7 Mn\GR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gUW9NXDRiY3XscJMh[XO|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kBk\WyuIHfyc5d1cCCjZoTldkA1KGSjeYOgZpkhS2WubDDUbZRmeiCEbIXlJIVv\C2yb3nueEBie3OjeTygSWM2OD1yLkG1JO69VQ>? NVqzbXF6OjJ6OEm1OlE>
human HepG2 cells MYnDfZRwfG:6aXRCpIF{e2G7 M3PI[GN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGhmeEd{IHPlcIx{KGGodHXyJFQ5KGi{czDifUBOXFRiYYPzZZktKFSFNUC9OEDPxE1? NGnHNZMzPDlzMEe2Oi=>
human A2780 cells NYe2[lBiWHKxbHnm[ZJifGmxbjDhd5NigQ>? MorYRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCDMke4NEBk\WyuczDhd5Nme3OnZDDhd{Bi[2O3bYXsZZRqd25ib3[gOG4hTE6DLDDJR|UxRTJ6IN88US=> MUWxPVMzODR6OR?=
HCT116 cells NUTO[Gp6TnWwY4Tpc44h[XO|YYm= NGfJNFdKdmirYnn0bY9vKG:oIHjpd5RwdmViaEOgdIhwe3Cqb4L5cIF1cW:wIHnuJGhEXDFzNjDj[YxteyCkeTDX[ZN1\XKwIHLsc5Qh[W6jbInzbZM> MoO2NVcyOjV{N{m=
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 (from reference)

Kinase Assay:[1]
  • 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]
  • 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.
Animal Research:[3]
  • Animal Models: Female SCID mice
  • Dosages: 15 mg/kg
  • Administration: Intraperitoneally

Solubility (25°C)

In vitro

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
1% DMSO+30% polyethylene glycol+1% Tween 80
For best results, use promptly after mixing.

30 mg/mL

Chemical Information

Molecular Weight 474.55
Formula

C26H30N6O3

CAS No. 827318-97-8
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CN1CCN(CC1)C2=CC=C(C=C2)C(=O)NC3=NNC4=C3CN(C4)C(=O)C(C5=CC=CC=C5)OC

In vivo Formulation Calculator (Clear solution)

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Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

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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.

Handling Instructions

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