Lapatinib (GW-572016) Ditosylate 化学構造
分子量: 925.46

高品質保証

文献中の引用(51)

カスタマーフィードバック(7)

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 Lapatinib (GW-572016) Ditosylateは有効EGFRとErbB2阻害剤、IC50それぞれ10.8と9.2nM。
ターゲット EGFR ErbB2
IC50 10.8 nM 9.2 nM [1]
In vitro試験 Lapatinib Ditosylate weakly inhibits the activity of ErbB4 with IC50 of 367 nM, and displays >300-fold selectivity for EGFR and ErbB2 over other kinases such as c-Src, c-Raf, MEK, ERK, c-Fms, CDK1, CDK2, p38, Tie-2, and VEGFR2. Lapatinib Ditosylate significantly inhibits receptor autophosphorylation of EGFR and ErbB2 in a dose-dependent manner with IC50 of 170 nM and 80 nM, respectively in HN5 cells; as well as 210 nM and 60 nM, respectively in BT474 cells. Unlike OSI-774 and Iressa (ZD1839) which preferentially inhibit the growth of the EGFR-overexpressing cells, Lapatinib Ditosylate inhibits the growth of both EGFR- and ErbB2-overexpressing cells. Lapatinib Ditosylate displays higher inhibitory activity against EGFR- or ErbB2-overexpressing cells with IC50 of 0.09-0.21 μM, compared with cells expressing low levels of EGFR or ErbB2 with IC50 of 3-12 μM, and exhibits ~100-fold selectivity over the normal fibroblast cells. Lapatinib Ditosylate potently inhibits the outgrowth of EGFR-overexpressing HN5 and A-431 cells, as well as ErbB2-overexpressing BT474 and N87 cells, and significantly induces G1 arrest of HN5 cells and apoptosis of BT474 cells, which are associated with inhibition of AKT phosphorylation. [1]
In vivo試験 Oral administration of Lapatinib Ditosylate (~100 mg/kg) twice daily significantly inhibits the growth of BT474 and HN5 xenografts in a dose-dependent manner. [1]
臨床試験 A Phase II study of Lapatinib in treating patients with recurrent prostate cancer has been completed.
特集

プロトコル (参考用のみ)

キナーゼアッセイ: [1]

In vitro kinase assays The IC50 values for inhibition of enzyme activity are generated by measuring inhibition of phosphorylation of a peptide substrate. The intracellular kinase domains of EGFR and ErbB2 are purified from a baculovirus expression system. EGFR and ErbB2 reactions are performed in 96-well polystyrene round-bottomed plates in a final volume of 45 μL. Reaction mixtures contain 50 mM 4-morpholinepropanesulfonic acid (pH 7.5), 2 mM MnCl2, 10 μM ATP, 1 μCi of [γ33P] ATP/reaction, 50 μM Peptide A [Biotin-(amino hexonoic acid)-EEEEYFELVAKKK-CONH2], 1 mM dithiothreitol, and 1 μL of DMSO containing serial dilutions of Lapatinib beginning at 10 μM. The reaction is initiated by adding the indicated purified type-1 receptor intracellular domain. The amount of enzyme added is 1 pmol/reaction (20 nM). Reactions are terminated after 10 minutes at 23°C by adding 45 μL of 0.5% phosphoric acid in water. The terminated reaction mix (75 μL) is transferred to phosphocellulose filter plates. The plates are filtered and washed three times with 200 μL of 0.5% phosphoric acid. Scintillation cocktail (50 μL) is added to each well, and the assay is quantified by counting in a Packard Topcount. IC50 values are generated from 10-point dose-response curves.

細胞アッセイ: [1]

細胞株 HFF, MCF-7, T47D, A-431, HN5, BT474, N87, CaLu-3, HB4a, and HB4a c5.2
濃度 Dissolved in DMSO, final concentrations ~100 μM
反応時間 72 hours
実験の流れ Cells are exposed to various concentrations of Lapatinib for 72 hours. Relative cell number is estimated using methylene blue staining. The absorbance at 620 nm is read in a Spectra microplate reader. Cell death and cell cycle analysis are assessed by propidium iodide staining and antibody detection of incorporated BrdUrd and staining with propidium iodide.

動物実験: [1]

動物モデル CD-1 nude female mice implanted s.c. with HN5 cells, and C.B-17 SCID female mice implanted s.c. with BT474 cells
製剤 Formulated in a vehicle of sulfo-butyl-ether-β-cyclodextrin 10% aqueous solution (CD10)
投薬量 ~100 mg/kg
投与方法 Orally twice daily

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 Lapatinib (GW-572016) Ditosylate SDF
分子量 925.46
化学式

C29H26ClFN4O4S.2C7H8O3S

CAS No. 388082-77-7
保管 3年-20℃
2年-80℃in solvent
別名 N/A
溶解度 (25°C) * In vitro DMSO 100 mg/mL (108.05 mM)
Water <1 mg/mL
Ethanol <1 mg/mL
In vivo 2% DMSO+30% PEG 300+ddH2O 10mg/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 N-(4-(3-fluorobenzyloxy)-3-chlorophenyl)-6-(5-((2-(methylsulfonyl)ethylamino)methyl)furan-2-yl)quinazolin-4-amine,di4-methylbenzenesulfonate

文献中の引用 (51)

Frequently Asked Questions

  • Question 1
    If I need to use S1028 for treating tumor-bearing mice with injection, how could I prepare the solution?

    Answer: S1028 Lapatinib Ditosylate can be dissolved in 2% DMSO/30% PEG 300/ddH2O at 10 mg/ml as clear solution.

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.

  • 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。

  • AZD8931 (Sapitinib)

    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。

  • 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: Lapatinib (GW-572016) Ditosylateを買う | Lapatinib (GW-572016) Ditosylate供給者 | Lapatinib (GW-572016) Ditosylateを購入する | Lapatinib (GW-572016) Ditosylate費用 | Lapatinib (GW-572016) Ditosylate生産者 | オーダーLapatinib (GW-572016) Ditosylate | Lapatinib (GW-572016) Ditosylate代理店
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
お問い合わせ