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PHA-739358

Cat. No. M1769

PHA-739358 Structure

Synonym: Danusertib

Size Price Availability Quantity
10mg USD 220 In stock
50mg USD 600 In stock
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Quality Control
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.

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 resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 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 resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 474.55
Formula C26H30N6O3
CAS Number 827318-97-8
Purity 100.00%
Solubility DMSO ≥95 mg/mL
Storage at -20°C
References

Targeting Aurora Kinases with Danusertib (PHA-739358) Inhibits Growth of Liver Metastases from Gastroenteropancreatic Neuroendocrine Tumors in an Orthotopic Xenograft Model.
Fraedrich K, et al. Clin Cancer Res. 2012 Sep 1;18(17):4621-32. PMID: 22753592.

Treatment of human pre-B acute lymphoblastic leukemia with the Aurora kinase inhibitor PHA-739358 (Danusertib).
Fei F, et al. Mol Cancer. 2012 Jun 21;11(1):42. PMID: 22721004.

Danusertib, an aurora kinase inhibitor.
Meulenbeld HJ, et al. Expert Opin Investig Drugs. 2012 Mar;21(3):383-93. PMID: 22242557.

The molecular mechanism studies of chirality effect of PHA-739358 on Aurora kinase A by molecular dynamics simulation and free energy calculations.
Cheng Y, et al. J Comput Aided Mol Des. 2011 Feb;25(2):171-80. PMID: 21222017.

Danusertib (formerly PHA-739358)--a novel combined pan-Aurora kinases and third generation Bcr-Abl tyrosine kinase inhibitor.
Gontarewicz A, et al. Recent Results Cancer Res. 2010;184:199-214. PMID: 20072840.

PHA-739358, a potent inhibitor of Aurora kinases with a selective target inhibition profile relevant to cancer.
Carpinelli P, et al. Mol Cancer Ther. 2007 Dec;6(12 Pt 1):3158-68. PMID: 18089710.

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  Catalog
Abmole Inhibitor Catalog 2017




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

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