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| 5mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
Sapitinib (formerly AZD8931; AZD-8931) is an orally bioactive, reversible and ATP competitive inhibitor of multiple kinases including EGFR, ErbB2/3 with potential antitumor activity. In cell-free assays, it inhibits EGFR and ErbB2/3 at IC50s of 4 nM, 3 nM, and 4 nM. In vitro, it exhibits strong anti-proliferative action against NSCLC cells.
| Targets |
EGFR (IC50 = 4 nM); ErbB2 (IC50 = 4 nM); HER3 (IC50 = 4 nM)
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|---|---|
| ln Vitro |
AZD8931 exhibits varying levels of potency in comparison to NSCLC and SCCHN cell lines. With a GI50 of 0.1 nM, AZD8931 exhibits high sensitivity to PC-9 cells (which have an EGFR activating mutation), while its activity against NCI-1437 cells is low, with a GI50 exceeding 10 μM. In PE/CA-PJ41, PE/CA-PJ49, DOK, and FaDu cells, AZD8931 shows greater efficacy against phospho-EGFR, phospho-erbB2, and phospho-erbB3 than either lapatinib or gefitinib does.[1]
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| ln Vivo |
AZD8931 exhibits antitumor activity in xenografts of PC-9, BT474c, Calu-3, LoVo, and FaDu. After acute treatment, AZD8931 may lower p-Akt, Ki67 expression, and p-ERK in BT474c xenografts. Additionally, AZD8931 induces the M30 apoptosis marker. Additionally, in LoVo xenografts, AZD8931 exhibits a higher proapoptotic effect than both lapatinib and gefitinib.[1]
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| Enzyme Assay |
Human EGFR and erbB2 intracellular kinase domains have been cloned and expressed in the baculovirus/Sf21 system. Using the ELISA method, the inhibitory activity of AZD8931 is assessed with ATP at Km concentrations (0.4 mM for erbB2 and 2 mM for EGFR).
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| Cell Assay |
AZD8931 is tested in a panel of NSCLC and SCCHN cell lines to ascertain its antiproliferative activity against cell lines grown in vitro. AZD8931 (0.001-10 μM) is added to cells and incubated for 96 hours. After incubating the MTS Colorimetric Assay reagent for four hours, the absorbance at 490 nm is measured using a spectrophotometer to determine the viable cell count.
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| Animal Protocol |
The mice used are severe combined immunodeficient and Swiss nude (nu/nu genotype). A 1% (v/v) solution of polyoxyethylenesorbitan monooleate (Tween 80) in deionized water is used to suspend AZD8931, GW572016, and ZD1839. Once (qd) or twice daily (bid), animals are given AZD8931 (6.25-50 mg/kg), GW572016 (100 mg/kg), ZD1839 (100-150 mg/kg), or vehicle control by oral gavage. Tumor growth characteristics dictate the duration of each study, with studies coming to an end when tumors reach less than 1 cm3. Tumor volume and percentage tumor growth inhibition are determined, and a standard t test is used to statistically analyze any changes in tumor volume (a P value of less than 0.05 is deemed statistically significant).
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| References |
| Molecular Formula |
C23H25CLFN5O3
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|---|---|
| Molecular Weight |
473.93
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| Exact Mass |
473.16
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| Elemental Analysis |
C, 58.29; H, 5.32; Cl, 7.48; F, 4.01; N, 14.78; O, 10.13
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| CAS # |
848942-61-0
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| Related CAS # |
848942-61-0 (free bade);1196531-39-1 (fumurate);
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| Appearance |
Solid powder
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| SMILES |
CNC(=O)CN1CCC(CC1)OC2=C(C=C3C(=C2)C(=NC=N3)NC4=C(C(=CC=C4)Cl)F)OC
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| InChi Key |
DFJSJLGUIXFDJP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H25ClFN5O3/c1-26-21(31)12-30-8-6-14(7-9-30)33-20-10-15-18(11-19(20)32-2)27-13-28-23(15)29-17-5-3-4-16(24)22(17)25/h3-5,10-11,13-14H,6-9,12H2,1-2H3,(H,26,31)(H,27,28,29)
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| Chemical Name |
2-[4-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]-N-methylacetamide
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| Synonyms |
AZD 8931; Sapitinib; AZD 8931; AZD8931
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.28 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.28 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.28 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 30% PEG400+0.5% Tween80+5% propylene glycol: 5 mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1100 mL | 10.5501 mL | 21.1002 mL | |
| 5 mM | 0.4220 mL | 2.1100 mL | 4.2200 mL | |
| 10 mM | 0.2110 mL | 1.0550 mL | 2.1100 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01284595 | Completed | Drug: [14C] AZD8931 | Healthy | AstraZeneca | March 2011 | Phase 1 |
| NCT01330758 | Completed | Drug: AZD8931 | Healthy | AstraZeneca | April 2011 | Phase 1 |
| NCT00637039 | Completed | Drug: AZD8931 | Advanced Solid Malignancies | AstraZeneca | February 2008 | Phase 1 |
| NCT00900627 | Completed | Drug: AZD8931 Drug: Paclitaxel |
Neoplasms Breast Cancer |
AstraZeneca | June 2009 | Phase 1 Phase 2 |
| NCT00879346 | Completed | Drug: AZD8931 | Healthy | AstraZeneca | March 2009 | Phase 1 |
Cellular phospho-EGFR, phospho-erbB2, and phospho-erbB3 geometric IC50 means and 95% confidence intervals for AZD8931, gefitinib, and lapatinib in the (A) PE/CA-PJ41 cell line, (B) PE/CA-PJ49 cell line, (C) DOK cell line, and (D) FaDu cell line. Clin Cancer Res. 2010 Feb 15;16(4):1159-69. |
Antitumor studies of AZD8931, gefitinib, and lapatinib using (A) BT474c, (B) Calu-3, (C) LoVo, (D) FaDu, and (E) PC-9 xenograft mouse models. |
Pharmacodynamic effects of AZD8931, lapatinib, and gefitinib. |
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