AZD8931 (Sapitinib) 化学構造
分子量: 473.93

高品質保証

カスタマーフィードバック(1)

Quality Control & MSDS

製品説明

  • Compare HER2 Inhibitors
    HER2製品生物活性の比較
  • 研究分野

製品の説明

生物活性

製品説明 AZD8931 (Sapitinib)は、EGFR、erbB2とerbB3の可逆的な、ATP競争的阻害剤で、IC50 がそれぞれ 4 nM、3 nM、4 nMです。
ターゲット

EGFR

ErbB2

ErbB3

IC50

4 nM

3 nM

4 nM [1]

In vitro試験 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試験 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]
臨床試験 Currently under Phase I clinical trial in Japanese patients with advanced solid malignancies.
特集

プロトコル (参考用のみ)

キナーゼアッセイ:

[1]

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.

細胞アッセイ:

[1]

細胞株 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,
濃度 0.001-10 μM
反応時間 96 hours
実験の流れ

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.

動物実験:

[1]

動物モデル BT474c, Calu-3, LoVo, FaDu and PC-9 xenografts in Swiss nude or severe combined immunodeficient (Charles River) mice.
製剤 Suspended in a 1% (v/v) solution of polyoxyethylenesorbitan monooleate (Tween 80) in deionized water
投薬量 6.25-50 mg/kg
投与方法 Gavage

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDogMonkeyBaboon
Weight (kg)0.020.151.80.40.0810312
Body Surface Area (m2)0.0070.0250.150.050.020.50.240.6
Km factor361285201220
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.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

参考

化学情報

Download AZD8931 (Sapitinib) SDF
分子量 473.93
化学式

C23H25ClFN5O3

CAS No. 848942-61-0
保管 2年-20℃
6月-80℃in solvent
別名 N/A
溶解度 (25°C) * In vitro DMSO 40 mg/mL (84.4 mM)
<1 mg/mL (<1 mM)
エタノール <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.
化学名 2-(4-(4-(3-chloro-2-fluorophenylamino)-7-methoxyquinazolin-6-yloxy)piperidin-1-yl)-N-methylacetamide

カスタマーフィードバック (1)


Click to enlarge
Rating
Source J Immunol, 2014, 192(2), 722-31. AZD8931 (Sapitinib) purchased from Selleck
Method Flow cytometry
Cell Lines htSMC
Concentrations 50 uM
Incubation Time 24 h
Results Treatment with the EGFR kinase inhibitor PD168393, the ErbB1/2/3 inhibitor AZD8931, the ErbB1/2/4 inhibitor PF299804, or cetuximab (block of EGFR ligand binding) reduced the LPS-induced release of CXCL8 , suggesting a critical role of EGFR/ErbB2 in this response.

文献中の引用 (5)

技術サポート&よくある質問(FAQ)

ストックの作り方、阻害剤の保管する方法、細胞実験や動物実験に注意すべきな点を全部含めており、製品を取扱う時よくあった質問に対して取扱説明書でお答えいたします。

電話番号: +1-832-582-8158 Ext:3月曜日〜金曜日 9:00 AM–5:00 PM (米国中部標準時)

他の質問がある場合は、お気軽くお問合せください。

* 必須

Related HER2 阻害剤

  • Erlotinib

    Erlotinib is an EGFR inhibitor with IC50 of 2 nM, >1000-fold more sensitive for EGFR than human c-Src or v-Abl.

  • R428 (BGB324)

    R428 (BGB324) is an inhibitor of Axl with IC50 of 14 nM, >100-fold selective for Axl versus Abl. Selectivty for Axl is also greater than Mer and Tyro3 (50-to-100- fold more selective) and InsR, EGFR, HER2, and PDGFRβ (100- fold more selective).

  • Pexidartinib (PLX3397)

    Pexidartinib (PLX3397) is an oral, potent mutil-targeted receptor tyrosine kinase inhibitor of CSF-1R, Kit, and Flt3 with IC50 of 20 nM, 10 nM and 160 nM, respectively. Phase 3.

  • PF-06463922

    PF-06463922 is a potent, dual ALK/ROS1 inhibitor with Ki of <0.02 nM, <0.07 nM, and 0.7 nM for ROS1, ALK (WT), and ALK (L1196M), respectively. Phase 1.

  • Lapatinib (GW-572016) Ditosylate

    Lapatinib (GW-572016) Ditosylateは有効EGFRとErbB2阻害剤、IC50それぞれ10.8と9.2nM。

  • AC480 (BMS-599626)

    AC480 (BMS-599626)は、HER1とHER2の選択的で口で有効な阻害剤で、IC50 がそれぞれ 20 nM と 30 nMです。

  • CP-724714

    CP-724714は、10nMのIC50によるerbB2の強力な、選択的な阻害剤です。

  • Neratinib (HKI-272)

    Neratinib(HKI-272)は、非常に選択的なHER2とEGFR阻害剤で、IC50 がそれぞれ 59 nM と 92 nMです。

  • Mubritinib (TAK 165)

    Mubritinib (TAK 165)は、6nMのIC50によるErbB2への強力な阻害剤です。

最近チェックしたアイテム

Tags: AZD8931 (Sapitinib)を買う | AZD8931 (Sapitinib)供給者 | AZD8931 (Sapitinib)を購入する | AZD8931 (Sapitinib)費用 | AZD8931 (Sapitinib)生産者 | オーダーAZD8931 (Sapitinib) | AZD8931 (Sapitinib)代理店
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
お問い合わせ