Sapitinib-AZD-8931-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemESapitinibCat. No.: HY-13050CAS No.: 848942-61-0Synonyms: AZD-8931分式: CHClFNO分量: 473.93作靶點: EGFR作通路: JAK/STAT Signaling; Protein Tyrosine Kinase/RTK儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 D

2、MSO : 33 mg/mL (69.63 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.1100 mL 10.5501 mL 21.1002 mL5 mM 0.4220 mL 2.1100 mL 4.2200 mL10 mM 0.2110 mL 1.0550 mL 2.1100 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。體內(nèi)實驗 Sapitinib (AZD8931) is suspended in

3、 1% (v/v) solution of polyoxyethylenesorbitan monooleate (Tween 80) indeionized water4.BIOLOGICAL ACTIVITY物活性Sapitinib (AZD-8931)可逆的，ATP競爭型 EGFR 抑制劑，對EGFR，ErbB2 和 ErbB3的 IC50 值分別為4，3 和1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE4 nM。IC50 & Target EGFR ErbB2 HER34 nM (IC50) 3 nM (IC50) 4 nM (IC5

4、0)體外研究 AZD8931 shows potent inhibitory effect on erbB2 in the ligand-independent MCF-7 cl24 cells, with IC50 of 59nM 1. AZD8931 (1 M) has no significant effect on EGFR expression level, but significantly inhibitsphosphorylation of Akt in a time- and dose-dependent manner in both SUM149 and FC-IBC-02

5、 cells.AZD8931 (0.01, 0.1, 1, or 2 M) inhibits proliferation and induces apoptosis in human IBC cells 2. At thecellular level, AZD8931 inhibits EGF-stimulated phosphorylation of EGFR in the KB cell line (IC50: 4 nM) andheregulin-stimulated phosphorylation of HER2 (IC50: 3 nM) and HER3 (IC50: 4 nM) i

6、n the MCF-7 cell line.However, AZD8931 exhibits no CYP P450 inhibition (IC50 10 M against 1A2, 2C9, 2C19, 2D6, and 3A4)3.體內(nèi)研究 AZD8931 (6.25-50 mg/kg, p.o.) significantly inhibits BT474c (breast), Calu-3 (NSCLC), LoVo (colorectal),FaDu (SCCHN), and PC-9 (NSCLC) tumor xenograft growth. AZD8931 is acti

7、ve in xenograft tumor modelsresponsive to EGFR inhibition alone (LoVo and PC-9) or EGFR or erbB2 inhibition (BT474c, Calu-3, andFaDu). AZD8931 causes pharmacodynamic changes in proliferation and apoptosis markers in human tumorxenograft models 1. AZD8931 (25 mg/kg, p.o.) significantly inhibits the g

8、rowth of SUM149 and FC-IBC-02cells in vivo in SCID mice 2. AZD8931 displays favorable oral pharmacokinetics in rat and dog (lowclearance and good bioavailability) and low human hepatocyte turnover (Clint 0.2 cm3). AZD8931, lapatinib, and gefitinib are suspended in a 1% (v/v) solution ofpolyoxyethyle

9、nesorbitan monooleate (Tween 80) in deionized water. Animals are given AZD8931 (6.25-502/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEmg/kg), Lapatinib (100 mg/kg), Gefitinib (100-150 mg/kg), or vehicle control once (qd) or twice daily (bid) byoral gavage. The duration of each study is determined

10、by tumor growth characteristics, with studies endingonce tumors reach 1 cm3. Tumor volume and percentage tumor growth inhibition are calculated andstatistical analysis of any change in tumor volume is carried out using a standard t test (P value of lower then0.05 is considered to be statistically si

11、gnificant).MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Hickinson DM, et al. AZD8931, an equipotent, reversible inhib

12、itor of signaling by epidermal growth factor receptor, ERBB2 (HER2), andERBB3: a unique agent for simultaneous ERBB receptor blockade in cancer. Clin Cancer Res. 2010 Feb 15;16(4):1159-69.2. Mu Z, et al. AZD8931, an equipotent, reversible inhibitor of signaling by epidermal growth factor receptor (E

13、GFR), HER2, and HER3:preclinical activity in HER2 non-amplified inflammatory breast cancer models. J Exp Clin Cancer Res. 2014 May 30;33:47.3. Barlaam B, et al. Discovery of AZD8931, an Equipotent, Reversible Inhibitor of Signaling by EGFR, HER2, and HER3 Receptors. ACSMed Chem Lett. 2013 May 31;4(8):742-6.4. Wang R, et al. Endothelial Cells Promote Colorectal Cancer Cell Survival by Activating the HER3-AKT Pathway in a Paracrine Fashion.Mol Cancer Res. 2018 Aug 21. pii: molcanres.0341.20