Antibodies
AZD8931 (Sapitinib)
- 貨號 Cat. No.
- S2192
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
AZD8931 (Sapitinib)
Catalog No.S21921 Product Citations
AZD8931 is a reversible, ATP competitive inhibitor of EGFR, ErbB2 and ErbB3 with IC50 of 4 nM, 3 nM and 4 nM, more potent than Gefitinib or Lapatinib against NSCLC cell, 100-fold more selective for the ErbB family than MNK1 and Flt. Phase 1/2.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | AZD8931 is a reversible, ATP competitive inhibitor of EGFR, ErbB2 and ErbB3 with IC50 of 4 nM, 3 nM and 4 nM, more potent than Gefitinib or Lapatinib against NSCLC cell, 100-fold more selective for the ErbB family than MNK1 and Flt. Phase 1/2. | |||||
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| Targets | EGFR | ErbB2 | ErbB3 | |||
| IC50 | 4 nM | 3 nM | 4 nM [1] | |||
| In vitro | 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. [1] | |||||
| 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. [1] | |||||
| Features | ||||||
Protocol(Only for Reference)
Kinase Assay:
| Isolated kinase assays | 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. |
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Cell Assay:
| Cell lines | 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, Calu-3, NCI-H2073, NCI-H1623, NCI-H522, NCI-H2085, NCI-H2030, NCI-H1703, NCI-H2291, NCI-H2135, NCI-H1975, NCI-H23, NCI-H1650, NCI-H1437, NCI-H3255, and NCI-H1666) |
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| Concentrations | 0.001-10 μM |
| Incubation Time | 96 hours |
| Method | 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. |
Animal Study:
| Animal Models | BT474c, Calu-3, LoVo, FaDu and PC-9 xenografts in Swiss nude or severe combined immunodeficient (Charles River) mice. |
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| Dosages | 6.25-50 mg/kg |
| Administration | Gavage |
| Solubility | 30% PEG400/0.5% Tween80/5% propylene glycol, 5 mg/mL |
References
Clinical Trial Information( data from http://clinicaltrials.gov)
| NCT Number | Recruitment | Conditions | Sponsor /Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT01151215 | Terminated | Neoplasms|Breast Neoplasms|Breast Cancer | AstraZeneca | 2010-06 | Phase 2 |
| NCT01284595 | Completed | Healthy | AstraZeneca | 2011-03 | Phase 1 |
| NCT01579578 | Terminated | Metastatic, Gastric or Gastro-oesophageal Junction, Cancer | AstraZeneca | 2012-04 | Phase 2 |
| NCT01596530 | Terminated | Breast Neoplasm | AstraZeneca | 2012-06 | Phase 1 |
| NCT01862003 | Not yet recruiting | Metastatic Colorectal Cancer|Recurrent Colorectal Cancer | University College, London|Cancer Research UK|AstraZeneca|UCL Biomedical Research Centre | 2013-08 | Phase 1 |
Chemical Information
Download AZD8931 (Sapitinib) SDF
| Molecular Weight (MW) | 473.93 |
|---|---|
| Formula | C23H25ClFN5O3 |
| CAS No. | 848942-61-0 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | 40 mg/mL (84 mM) |
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| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | <1 mg/mL (<1 mM) | ||
| In vivo | 30% PEG400/0.5% Tween80/5% propylene glycol, | 5 mg/mL | |
| * <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. | |||
| Chemical Name | 2-(4-(4-(3-chloro-2-fluorophenylamino)-7-methoxyquinazolin-6-yloxy)piperidin-1-yl)-N-methylacetamide |
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Preparing Stock Solutions
| Stock Solution (1ml DMSO) | 1mM | 10mM | 20mM | 30mM |
|---|---|---|---|---|
| Mass(mg) | 0.47393 | 4.7393 | 9.4786 | 14.2179 |
Product Citations (1)
Smooth Muscle Cells Relay Acute Pulmonary Inflammation via Distinct ADAM17/ErbB Axes. [Dreymueller D ,et al. J Immunol 2013;192(2):722-31]
PubMed: 24342803
