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XL147

Cat. No. M1879
XL147 Structure
Synonym:

SAR245408

Size Price Availability Quantity
5mg USD 110 In stock
10mg USD 140 In stock
50mg USD 385 In stock
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Quality Control
  • Current batch:
  • Purity >99%
  • COA
  • MSDS
Biological Activity

XL147 (SAR245408) is a novel small molecule PI3K inhibitor. Activation of the PI3 kinase pathway occurs frequently in many cancers and is implicated in tumor cell proliferation, survival, and resistance to chemotherapy and radiotherapy. XL147 demonstrated cytotoxic activity, with a median relative IC(50) value of 10.9 µM (range 2.7-24.5 µM) in vitro. Also XL147 was well tolerated in vivo, all 44 tested xenograft models were evaluable for efficacy. XL147 (SAR245408) induced tumor growth inhibition meeting criteria for intermediate EFS T/C activity (EFS T/C > 2) in 4 of 37 (11%) solid tumor xenografts. Knockdown of HER3 with siRNA or cotreatment with the HER2 inhibitors trastuzumab or lapatinib enhanced XL147-induced cell death and inhibition of pAKT and pS6 in HER2(+) cells. Trastuzumab and lapatinib each synergized with XL147 for inhibition of pAKT and growth of established BT474 xenografts.

Protocol
Cell Experiment
Cell lines panel of cell lines, such as BT474, PC-3 and MCF-7
Preparation method Cell-based assays.
Cell lines were obtained from the ATCC in 2001–2005 and maintained in culture conditions at 37°C under 5% CO2 as previously described. For PI3K pathway status assessment following EGF treatment, the culture medium was replaced with test compounds dissolved in serum-free DMEM containing 0.3% DMSO. After incubation for 3 hours, cells were stimulated with 100 ng/mL of EGF (R&D Systems, 236-EG) for 10 minutes and Western immunoblot analysis of cell lysates was performed as previously described. Assessment of mTOR pathway status in Ramos cells was performed as previously described. Cellular proliferation was assessed as previously described using the Cell Proliferation ELISA, bromodeoxyuridine (BrdUrd) chemiluminescence kit.
Concentrations 0~30 μM
Incubation time 48 or 72 h
Animal Experiment
Animal models MCF-7 and OVCAR cells tumour xenograft model
Formulation sterile water/10 mmol/L HCl or water
Dosages 30, 100mg/kg qd or 300mg/kg twice weekly
Administration oral gavage
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 448.52
Formula C21H16N6O2S2
CAS Number 956958-53-5
Purity >99%
Solubility DMSO 80 mg/mL
Storage at -20°C
References

The Selective PI3K Inhibitor XL147 (SAR245408) Inhibits Tumor Growth and Survival and Potentiates the Activity of Chemotherapeutic Agents in Preclinical Tumor Models.
Foster P, et al. Mol Cancer Ther. 2015 Apr;14(4):931-40. PMID: 25637314.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: XL147, SAR245408 supplier, PI3K, inhibitors

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