培利替尼作用機(jī)制 - Medchemexpress - MCE中國

1、Product Data SheetPelitinibCat. No.: HY-32718CAS No.: 257933-82-7分式: CHClFNO分量: 467.92作靶點(diǎn): EGFR; Src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(shí)驗(yàn) DMSO : 25 mg/mL (53.43 mM; Need ultrasonic)H2O : 0.1 mg/mL (insolubl

2、e)SolventMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 2.1371 mL 10.6856 mL 21.3712 mL5 mM 0.4274 mL 2.1371 mL 4.2742 mL10 mM 0.2137 mL 1.0686 mL 2.1371 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；旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲存時，請?jiān)?6 個內(nèi)使，-20C 儲存時，請?jiān)?1 個內(nèi)使。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)動物和給藥式選

3、擇適當(dāng)?shù)娜芙獍浮Ｒ韵氯芙獍付颊埾劝凑?In Vitro 式配制澄清的儲備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的式助溶1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.34 mM); Clear solution此案可獲得 2.5 mg/mL (5.34 mM，飽和度未知) 的澄清溶液。以

4、 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.34 mM); Suspended solution; Need ultrasonicPage 1 of 2 www.MedChemE此案可獲得 2.5 mg/mL (5.34 mM) 的均勻懸濁液，懸濁液可于服和腹腔注射。以

5、1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合均勻。BIOLOGICAL ACTIVITY物活性 Pelitinib (EKB-569;WAY-EKB 569)是可逆的 EGFR 抑制劑，IC50 值為38.5 nM。也可輕微抑制Src，MEK/ERK 和 ErbB2， IC50 值分別為282，800，和1255 nM。IC & Target EGFR38.5 nM (IC50)體外研究 Pelitini has much greater inhibitory activity against th

6、e EGFR kinase than against Src, MEK/ERK, Cdk4, c-Met, Raf andErbB2, for example, the IC50 for EGFR is 32-fold lower than the IC50 for the closely related ErbB2. Pelitinib results in adramatic reduction in EGFR phosphorylation but no change in the total amount of EGFR protein. It requires at least10-

7、fold more drug to equivalently inhibit ErbB2 phosphorylation in similar assays, and EKB-569 does not blockphosphorylation of another receptor tyrosine kinase (c-Met) assessed in the same manner1. EKB-569 is a potentinhibitor of proliferation in NHEK, A431, and MDA-468 cells (IC50=61, 125, and 260 nM

8、, respectively) but not MCF-7cells (IC50=3600 nM). EKB-569 is also a potent inhibitor of EGF-induced phosphorylated EGF-R (pEGF-R) in A431 andNHEK cells (IC50=20-80 nM)1.體內(nèi)研究 A single oral dose of 10 mg/kg EKB-569 inhibits EGFR phosphorylation in A431 xenografts within 60 minutes. Twenty-four hours

9、later, EGFR activity is still inhibited by over 50% by this single oral dose. The half-life of EKB-569 in mouse plasma is about 2 hours1.PROTOCOLCell Assay 1 For experiments using cells in culture, A431 cells or 3T3/c-erbB-2 cells over-expressing c-erbB2 are are treated withvarious concentrations of

10、 EKB-569 for 2.75 h before co-incubation with 100 ng/mL EGF (A431 cells) or no growthfactor (3T3/c-erbB-2 cells) for 0.25 h. Cells are ished twice with cold phosphate-buffered saline (PBS) before adding tolysis buffer for 20 min on ice, before immunoprecipitation and SDSimmunoblotting1.MCE has not i

11、ndependently confirmed the accuracy of these methods. They are for reference only.Animal Mice: For in vivo experiments, athymic nu/nu female mice are implanted subcutaneously with 5106 A431 tumorAdministration 1 cells. When tumors reach a mass of 200-300 mg, animals are treated with a single dose of

12、 10 mg/kg EKB-569 in pH2.0 water per gavage. Tumors from control and drug-treated animals are excised and minced into 1-mm pieces foranlysis1.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.

13、 Harvard Medical School LINCS LIBRARYSee more customer validations on HYPERLINK www.MedChemE www.MedChemEPage 2 of 3 www.MedChemEREFERENCES1. Torrance CJ, et al. Combinatorial chemoprevention of intestinal neoplasia. Nat Med. 2000 Sep;6(9):1024-8.2. Nunes M, et al. Phosphorylation of extracellular signal-regulated kinase 1 and 2, protein kinase B, and signal transducer and activator of transcription 3are differently inhibited by an epidermal growth factor receptor inhibitor, EKB-569, in tumor cells and normal human keratinocytes. Mol Cancer Ther. 2004Jan;3(1):21-7.McePdfHeightC