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PHA-739358 (Danusertib)

Cat. No. M1769
PHA-739358 (Danusertib) Structure
Synonym:

Danusertib

Size Price Availability Quantity
Free Sample 0.5 mg  USD 0 In stock
10mM*1mL in DMSO USD 112  USD112 In stock
2mg USD 70  USD70 In stock
5mg USD 110  USD110 In stock
10mg USD 200  USD200 In stock
50mg USD 590  USD590 In stock
100mg USD 880  USD880 In stock
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Quality Control
  • Current batch:
  • Purity >98%
  • COA
  • MSDS
Biological Activity

PHA-739358 (Danusertib) is a small molecule with low nanomolar activity against all aurora kinases (AKs) with IC50 value of 13 nM for aurora-A and 79 nM for aurora-B respectively. PHA-739358 (Danusertib) also inhibits other cancer relevant tyrosine kinases such as wild type and mutated ABL, RET, TRK-A and FGFRs.

Customer Product Validations & Biological Datas
Source PLoS One (2014). Figure 1. PHA-739358
Method MTT assay
Cell Lines Ba/F3 cells
Concentrations 200 nM
Incubation Time 48 h
Results Accordingly, IC50 values were in a range of 150 nM for PHA-739358 and 10 nM for R763/AS703569, independent of the BCR-ABL mutation status
Protocol
Cell Experiment
Cell lines wild-type (HCT-116 cells )or p53 −/− MEF (A2780) cells
Preparation method Analysis of Cell Proliferation Analysis was done as previously described (20). Briefly, cells were seeded at different densities in 24-well plates with the appropriate medium. After 24 h, cells were treated with compound and incubated for 72 h at 37°C in 5% CO2 atmosphere. At the end of the incubation time, cells were detached from each plate and counted using a cell counter (Coulter Counter-Beckman). IC50 values were calculated using percent of growth versus untreated control.
Concentrations 1μM
Incubation time 24 or 48 hr
Animal Experiment
Animal models Mice bearing established A2780 and HCT-116 tumor xenografts
Formulation saline
Dosages 30 mg/kg bd for 5 consecutive days
Administration i.v.
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

Chemical Information
Molecular Weight 474.55
Formula C26H30N6O3
CAS Number 827318-97-8
Purity >98%
Solubility DMSO 50 mg/mL
Storage at -20°C
References

[1] Fraedrich K, et al. Clin Cancer Res. Targeting Aurora Kinases with Danusertib (PHA-739358) Inhibits Growth of Liver Metastases from Gastroenteropancreatic Neuroendocrine Tumors in an Orthotopic Xenograft Model.

[2] Fei F, et al. Mol Cancer. Treatment of human pre-B acute lymphoblastic leukemia with the Aurora kinase inhibitor PHA-739358 (Danusertib).

[3] Meulenbeld HJ, et al. Expert Opin Investig Drugs. Danusertib, an aurora kinase inhibitor.

[4] Cheng Y, et al. J Comput Aided Mol Des. The molecular mechanism studies of chirality effect of PHA-739358 on Aurora kinase A by molecular dynamics simulation and free energy calculations.

[5] Gontarewicz A, et al. Recent Results Cancer Res. Danusertib (formerly PHA-739358)--a novel combined pan-Aurora kinases and third generation Bcr-Abl tyrosine kinase inhibitor.

[6] Carpinelli P, et al. Mol Cancer Ther. PHA-739358, a potent inhibitor of Aurora kinases with a selective target inhibition profile relevant to cancer.

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Keywords: PHA-739358 (Danusertib), Danusertib supplier, Aurora Kinase, inhibitors

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