Apatinib-YN968D1-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEApatinibCat. No.: HY-13342CAS No.: 1218779-75-9Synonyms: YN968D1分式: CHNOS分量: 493.58作靶點: VEGFR; RET; Autophagy作通路: Protein Tyrosine Kinase/RTK; Autophagy儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體

2、外實驗 DMSO : 32 mg/mL (64.83 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.0260 mL 10.1301 mL 20.2601 mL5 mM 0.4052 mL 2.0260 mL 4.0520 mL10 mM 0.2026 mL 1.0130 mL 2.0260 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，并請注意儲備液的保存式和期限。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?，配制前請先配制澄?/p>

3、的儲備液，再依次添加助溶劑(為保證實驗結(jié)果的可靠性，體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲備液可以根據(jù)儲存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.07 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.07 mM); Clear solution1/3 Maste

4、r of Small Molecules 您邊的抑制劑師www.MedChemE3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.07 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Apatinib種選擇性的 VEGFR2 抑制劑，IC50 為 1 nM。Apatinib也有效抑制Ret，c-Kit 和 c-Src活性，IC50s分別為 13，429 和 530 nM。IC50 & Target VEGFR21 nM (IC50)體外研究 Apatinib (YN968D1) sligh

5、tly inhibits proliferation of HUVEC stimulated by 20% FBS (IC50=23.4 M), whereasApatinib significantly inhibits proliferation stimulated by 20 ng/mL VEGF (IC50=0.17 M). The IC50 values ofSunitinib are lower under the same conditions (7.4 M and 0.034 M, respectively). 1 M Apatinibsignificantly inhibi

6、ts the migration of HUVEC induced by FBS, but does not affect proliferation of HUVEC,indicating that the inhibitory effect of Apatinib on FBS-induced migration is not due to the suppression ofproliferation. At a concentration of 1 M, Sunitinib also inhibits the migration of HUVEC 1.體內(nèi)研究 The antitumo

7、r potential of Apatinib (YN968D1) is evaluated in six human tumor xenografts inimmunodeficient mice. Once-daily oral administration of Apatinib produces a dose-dependent inhibition oftumor growth in all tumor models examined. Statistically significant growth inhibition is obtained with 50mg/kg per d

8、ay Apatinib in three of five tumor xenografts tested. Each tumor xenograft model is significantlygrowth inhibited by Apatinib at the dose of 100 kg/day. Similar tumor growth inhibition is observed (T/C%, 8%to 18%) in mice following treatment with Apatinib at the dose of 200 kg/day. Full growth inhib

9、ition profiles areshown for three of the xenografts. Compared with the control animals, no effect of Apatinib treatment onbodyweight is observed at any dose level, which suggested that Apatinib is well tolerated 1.PROTOCOLCell Assay 1 The following human tumor cell lines are used: Ls174t, HCT 116, S

10、GC-7901, HT-29, A549, NCI-H460, Mo7e,A431, BT474 and NIH-3T3. The cells are cultured in RPMI-1640 or DMEM supplemented with 10% FBS at37C with 5% carbon dioxide. Primary HUVEC are isolated from segments of normal-term cords by digestionwith type I collagenase, and are pooled and cultured in Medium 1

11、99 (M199) supplemented with 20% FBSand endothelial cell growth factor. Cells in the exponential growth phase are used in the experiments. TheHUVEC are seeded into 96-well plates. After 24 h of incubation, cells are exposed to the test agents (vehicleas control) together with 20 ng/mL VEGF or 20% FBS

12、 for another 72 h. After fixation with 10% trichloroaceticacid, the cells are stained with 0.4% sulforhodamine B for 30 min at 37C and then washed with 1% aceticacid. Tris is added to dissolve the complex, and the optical density is measured at 520 nm 1.MCE has not independently confirmed the accura

13、cy of these methods. They are for reference only.Animal Mice 1Administration 1 The effects of Apatinib (YN968D1) on tumor growth are tested against various human tumors grown2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEsubcutaneously in BALB/cA nude mice. Tumor growth is initiated by subcutaneou

14、s inoculation of cells intomice. Tumors are allowed to establish and grow to 100-300 mm3, at which time the mice are randomized intoexperimental groups. Apatinib is administered once daily by oral gavage for the indicated periods. Incombination treatment experiments, mice are administered Apatinib a

15、lone by oral gavage; 5-FU, oxaliplatin,docetaxel and doxorubicin alone by intravenous injection; or Apatinib in combination with each cytotoxic drugat the indicated dose and schedule. Tumor volume and bodyweight are monitored every other day or every 3days, with the means indicated for groups of six

16、 (treated) or 12 (vehicle control) animals. Tumor volumes aredetermined by measuring the largest diameter (a) and its perpendicular (b) according to the formula (ab2)/2.The evaluation index for inhibition is the relative tumor growth ratio according to the equation: T/C (%)=meanincrease of tumor vol

17、umes of treated groupsmean increase of tumor volumes of control groups100%.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. J Med Chem. 2017 Apr 13;60(7):2930-2943. Cell Oncol (Dordr). 2019 Jul 20. Immunol Res. 2019 Jul 10. BMC Gastroenterol. 2018 Nov 6;18(1):169.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Tian S, et al. YN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase with pot