product name AZD8931 (Sapitinib)
Description: AZD8931 (also known as Sapitinib) is a highly potent, reversible, and ATP competitive inhibitor of EGFR, ErbB2 and ErbB3 with IC50 of 4 nM, 3 nM and 4 nM in cell-free assays, it is more potent than Gefitinib or Lapatinib against NSCLC cell, and is 100-fold more selective for the ErbB family than MNK1 and Flt. AZD8931 binds to and inhibits erbB tyrosine receptor kinases, which may result in the inhibition of cellular proliferation and angiogenesis in tumors expressing erbB.
References: Clin Cancer Res. 2010 Feb 15;16(4):1159-69.
473.93
Formula
C23H25ClFN5O3
CAS No.
848942-61-0
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 40 mg/mL (84.4 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
30% PEG400+0.5% Tween80+5% propylene glycol: 5 mg/mL
Synonyms
Sapitinib
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19417038
| In Vitro |
In vitro activity: AZD8931 shows different potency to NSCLC and SCCHN cell lines. AZD8931 has high sensitivity to PC-9 cells (EGFR activating mutation) with GI50 of 0.1 nM and low activity to NCI-1437 cells with GI50 above 10 μM. AZD8931 exhibits more potency against phospho-EGFR, phospho-erbB2 and phospho-erbB3 than either lapatinib or gefitinib in PE/CA-PJ41, PE/CA-PJ49, DOK and FaDu cells. Kinase Assay: The intracellular kinase domains of human EGFR and erbB2 are cloned and expressed in the baculovirus/Sf21 system. The inhibitory activity of AZD8931 is determined with ATP at Km concentrations (0.4 mM for erbB2 and 2 mM for EGFR) using the ELISA method. Cell Assay: To determine the antiproliferative activity against cell lines grown in vitro, AZD8931 is tested in a panel of NSCLC and SCCHN cell lines. Cells are incubated for 96 hours with AZD8931 (0.001-10 μM). Viable cell number is determined by 4 hours of incubation with MTS Colorimetric Assay reagent and absorbance measured at 490 nm on a spectrophotometer. Head and neck tumor cell lines (KYSE-30, OE21, PE/CA-PJ15, PE/CA-PJ34 (clone C12), PE/CA-PJ41 (clone D2), PE/CA-PJ49, DOK, Detroit562, RPMI2650, SCC-4, SCC-9, SCC-25, CAL 27, SW579, FaDu, Hs 840.T, KB, KYSE-450, and HEp-2, HN5) and NSCLC cell lines (PC-9). |
|---|---|
| In Vivo | AZD8931 reveals antitumor activity in BT474c, Calu-3, LoVo, FaDu and PC-9 xenografts. AZD8931 could reduce p-Akt, Ki67 expression and p-ERK in BT474c xenografts following acute treatment. AZD8931 also causes induction of the M30 apoptosis marker. Furthermore, AZD8931 shows greater proapoptotic effect compared with gefitinib and lapatinib in LoVo xenografts. |
| Animal model | BT474c, Calu-3, LoVo, FaDu and PC-9 xenografts in Swiss nude or severe combined immunodeficient (Charles River) mice. |
| Formulation & Dosage | Suspended in a 1% (v/v) solution of polyoxyethylenesorbitan monooleate (Tween 80) in deionized water; 6.25-50 mg/kg; oral gavage |
| References | Clin Cancer Res. 2010 Feb 15;16(4):1159-69. |
