司馬沙尼作用機(jī)制 - Medchemexpress - MCE中國

1、Product Data SheetSemaxinibCat. No.: HY-10374CAS No.: 204005-46-9分式: CHNO分量: 238.28作靶點(diǎn): VEGFR作通路: 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)體外實驗 DMF : 50 mg/mL (209.84 mM)DMSO : 22.5 mg/mL (94.43 mM; Need ultrasonic and warming)H2O : 0.1 mg

2、/mL (insoluble)* means soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 4.1967 mL 20.9837 mL 41.9674 mL5 mM 0.8393 mL 4.1967 mL 8.3935 mL10 mM 0.4197 mL 2.0984 mL 4.1967 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。-

3、80C 儲存時，請在 6 個內(nèi)使，-20C 儲存時，請在 1 個內(nèi)使。體內(nèi)實驗請根據(jù)您的實驗動物和給藥式選擇適當(dāng)?shù)娜芙獍?。以下溶解案都請先按?In Vitro 式配制澄清的儲備液，再依次添加助溶劑：為保證實驗結(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)實驗的作液，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% DMF 90% corn oil2.Solubility: 2.5 mg/mL (10.49 mM); Clear solution請依序添加

4、每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.25 mg/mL (9.44 mM); Suspended solution; Need ultrasonic此案可獲得 2.25 mg/mL (9.44 mM) 的均勻懸濁液，懸濁液可于服和腹腔注射。以 1 mL 作液為例，取 100 L 22.5 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Page 1 of 2 www.MedChemE50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。

5、BIOLOGICAL ACTIVITY物活性 Semaxinib (SU5416)是有效，選擇性的 VEGFR (Flk-1/KDR) 抑制劑，IC50 為1.23 M。IC & Target Flk-11.23 M (IC50)體外研究 Semaxinib (SU5416) inhibits VEGF-driven mitogenesis in a dose-dependent manner with an IC50 of 0.040.02 M(n=3). In contrast, Semaxinib (SU5416) blocks FGF-dependent mitogenesis of

6、HUVECs with an IC50 of 50 M (n=10).An IC50 of 20.265.2 M, which is about 20-fold less in potency on PDGF-dependent autophosphorylation, isobserved when SU5416 is tested in NIH 3T3 cells overexpressing the human PDGF receptor 1.體內(nèi)研究 Daily administration of Semaxinib (SU5416) (i.p., 3 mg/kg/day) inhib

7、its the local growth of C6 tumors in the colon. Acomparable level of growth inhibition (62% by day 16; P=0.001) is observed for tumors growing in the colon incomparison with ones growing in the hindflank region (54% by day 18; P=0.001). These results indicate thatSemaxinib (SU5416) could inhibit tum

8、or growth at a site other than the subcutaneous implantation site, where thepreexisting vasculature may be different1. Daily treatment with Semaxinib (SU5416) (25 mg/kg) results in asignificantly lower tumor growth rate with tumor masses of up to 8% of that present in control animals by day 22after

9、implantation. Inhibition of tumor growth is clearly preceded by a marked reduction of the tissue area covered bythe newly formed glioma microvasculature in the Semaxinib-treated group, indicating a reduced initial tumorvascularization2.PROTOCOLCell Assay 3T3Her2 and 488G2M2 are NIH3T3 fibroblast cel

10、l lines engineered to overexpress Her2 and to express human PDGF-BB and human PDGF receptor . Both cell lines are cultured in DMEM supplemented with 2% CS and 2 mM L-glutamine. C6, Calu 6, A375, A431, and SF767T are plated in their respective growth medium at 2103 cells/100 L/well in 96-well, flat-b

11、ottomed plates. Semaxinib (SU5416) is serially diluted in media containing DMSO (0.5%) andadded to cultures of tumor cells 1 day after the initiation of culture. Cell growth is measured after 96 h using thesulforhodamine B method. IC50s are calculated by curve fitting using four-parameter analysis1.

12、MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice1Administration 13 Female BALB/c nu/nu mice (20-22 g; 12 weeks of age) are used. Aseptic technique is used during this surgicalprocedure. A small midline incision (1 cm) is made in the abdomen d

13、irectly over the colon. C6 cells are implanted(0.5106 cells/animal) under the serosa of the colon using a 27-gauge needle. After implantation, all exposedsections of the intestine are returned into the abdominal cavity. The peritoneum and skin are closed using a 6.0surgical suture and wound clips. T

14、he wound clips are removed 7 days after surgery. Animals are treated once dailywith a 50 L i.p. bolus injection of either Semaxinib (SU5416) or DMSO, beginning 1 day after implantation.Approximately 13-16 days after implantation, animals are euthanized, and local tumor growth on the colon isquantita

15、ted either by weighing the tumors or by measuring the tumors using venier calipers. Tumor volumes arecalculated as the product of lengthwidthheight.Rats3Male Sprague Dawley rats (n=60, 6-8 wk) are randomly divided among five groups: control (Con), Semaxinib (SU),pneumonectomy (PNx), Semaxinib+hypoxi

16、a (SuHx), and Semaxinib+PNx (SuPNx). The SuHx protocol is employed.Page 2 of 3 www.MedChemEBriefly, animals are injected with Semaxinib (25 mg/kg) dissolved in carboxymethylcellulose (CMC) and exposed tohypoxia (10%) for 4 wk followed by re-exposure to normoxia. PNx animals underwent a left pneumone

17、ctomy. Twodays following PNx surgery an injection of Semaxinib is administered (25 mg/kg). The Con group received only thesolvent CMC. Echocardiography is utilized at baseline (prehypoxia/presurgery), week 2, and week 6 to determinecardiac morphometry and function. Two and six weeks postsurgery/post

18、hypoxia animals are anesthetized and rightventricle (RV) and left ventricle (LV) pressure measurements via catheterization are performed.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) Transl Stroke Res. 2018 Oct;9(5):540-548. J Am Heart Ass

19、oc. 2019 Mar 5;8(5):e011227. Am J Respir Cell Mol Biol. 2019 Jun 18. Acta Pharmacol Sin. 2020 May 12. Am J Pathol. 2019 Dec 10. pii: S0002-9440(19)30758-8.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Fong TA, et al. SU5416 is a potent and selective inhibitor of th

20、e vascular endothelial growth factor receptor (Flk-1/KDR) that inhibits tyrosine kinasecatalysis, tumor vascularization, and growth of multiple tumor types. Cancer Res, 1999, 59(1), 99-106.2. Vajkoczy P, et al. Inhibition of tumor growth, angiogenesis, and microcirculation by the novel Flk-1 inhibito