Apatinib-YN968D1-DataSheet-生命科学试剂-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作靶点: VEGFR; RET; Autophagy作通路: Protein Tyrosine Kinase/RTK; Autophagy储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体

2、外实验 DMSO : 32 mg/mL (64.83 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液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请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清

3、的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.07 mM); Clear solution2. 请依序添加每种溶剂： 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 您边的抑制剂师www.MedChemE3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.07 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Apatinib种选择性的 VEGFR2 抑制剂，IC50 为 1 nM。Apatinib也有效抑制Ret，c-Kit 和 c-Src活性，IC50s分别为 13，429 和 530 nM。IC50 & Target VEGFR21 nM (IC50)体外研究 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.体内研究 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 您边的抑制剂师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.户使本产品发表的科研献 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