1、Product Data SheetApatinibCat. No.: HY-13342CAS No.: 1218779-75-9分式: CHNOS分量: 493.58作靶點(diǎn): VEGFR; RET; c-Kit; Src; Autophagy作通路: Protein Tyrosine Kinase/RTK; Autophagy儲(chǔ)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 : 250 mg/mL (506.50 mM)* means soluble, but satura

2、tion unknown.SolventMass1 mg 5 mg 10 mgConcentration制備儲(chǔ)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(qǐng)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(chǔ)備液；旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)內(nèi)使，-20C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?1 個(gè)內(nèi)使。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)

3、您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍浮Ｒ韵氯芙獍付颊?qǐng)先按照 In Vitro 式配制澄清的儲(chǔ)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(chǔ)備液可以根據(jù)儲(chǔ)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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的式助溶1. 請(qǐng)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 solution此案可獲得 2.5 mg/mL (5.07 mM，飽和度

4、未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)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(qǐng)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 solutionPage 1 of 2 www.MedChemE此案可獲得 2.5 mg/mL (5.07 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L

5、 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合均勻。3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.07 mM); Clear solution此案可獲得 2.5 mg/mL (5.07 mM，飽和度未知) 的澄 溶液，此案不適于實(shí)驗(yàn)周 期在半個(gè)以上的實(shí)驗(yàn)。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Apatinib (YN968D1)種服物可利

6、的酪氨酸激酶抑制劑，選擇性靶向VEGFR-2，IC50 為 1 nM。Apatinib(YN968D1) 有效抑制 Ret，c-Kit 和 c-Src 活性，IC50 分別為 13，429 和 530 nM。Apatinib (YN968D1) 也抑制 VEGFR-2、c-kit 和 PDGFR 的細(xì)胞磷酸化。IC & Target VEGFR21 nM (IC50)體外研究 Apatinib (YN968D1) slightly inhibits proliferation of HUVEC stimulated by 20% FBS (IC50=23.4 M), whereas Apati

7、nibsignificantly inhibits proliferation stimulated by 20 ng/mL VEGF (IC50=0.17 M). The IC50 values of Sunitinib are lowerunder the same conditions (7.4 M and 0.034 M, respectively). 1 M Apatinib significantly inhibits the migration ofHUVEC induced by FBS, but does not affect proliferation of HUVEC,

8、indicating that the inhibitory effect of Apatinib onFBS-induced migration is not due to the suppression of proliferation. At a concentration of 1 M, Sunitinib alsoinhibits the migration of HUVEC1.Apatinib promotes ROS-dependent apoptosis and autophagy mainly via the inhibition of the Nrf2/HO-1-GSHsi

9、gnaling pathway1.體內(nèi)研究 The antitumor potential of Apatinib (YN968D1) is evaluated in six human tumor xenografts in immunodeficient mice.Once-daily oral administration of Apatinib produces a dose-dependent inhibition of tumor growth in all tumor models examined. Statistically significant growth inhibi

10、tion is obtained with 50 mg/kg per day Apatinib in three of fivetumor xenografts tested. Each tumor xenograft model is significantly growth inhibited by Apatinib at the dose of 100kg/day. Similar tumor growth inhibition is observed (T/C%, 8% to 18%) in mice following treatment with Apatinib atthe do

11、se of 200 kg/day. Full growth inhibition profiles are shown for three of the xenografts. Compared with thecontrol animals, no effect of Apatinib treatment on bodyweight is observed at any dose level, which suggested thatApatinib is well tolerated1.PROTOCOLCell Assay 1 The following human tumor cell

12、lines are used: Ls174t, HCT 116, SGC-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 at 37C with 5%carbon dioxide. Primary HUVEC are isolated from segments of normal-term cords by digestion with type Icollagenase, and a

13、re pooled and cultured in Medium 199 (M199) supplemented with 20% FBS and endothelial cellgrowth factor. Cells in the exponential growth phase are used in the experiments. The HUVEC are seeded into 96-wellplates. After 24 h of incubation, cells are exposed to the test agents (vehicle as control) tog

14、ether with 20 ng/mL VEGFor 20% FBS for another 72 h. After fixation with 10% trichloroacetic acid, the cells are stained with 0.4%sulforhodamine B for 30 min at 37C and then washed with 1% acetic acid. Tris is added to dissolve the complex, andthe optical density is measured at 520 nm1.MCE has not i

15、ndependently confirmed the accuracy of these methods. They are for reference only.Page 2 of 3 www.MedChemEAnimal Mice1Administration 1 The effects of Apatinib (YN968D1) on tumor growth are tested against various human tumors grown subcutaneouslyin BALB/cA nude mice. Tumor growth is initiated by subc

16、utaneous inoculation of cells into mice. Tumors are allowedto establish and grow to 100-300 mm3, at which time the mice are randomized into experimental groups. Apatinib isadministered once daily by oral gavage for the indicated periods. In combination treatment experiments, mice areadministered Apa

17、tinib alone by oral gavage; 5-FU, oxaliplatin, docetaxel and doxorubicin alone by intravenousinjection; or Apatinib in combination with each cytotoxic drug at the indicated dose and schedule. Tumor volume andbodyweight are monitored every other day or every 3 days, with the means indicated for group

18、s of six (treated) or 12(vehicle control) animals. Tumor volumes are determined 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 accordingto the equation: T/C (%)=mean increase of t

19、umor volumes of treated groupsmean increase of tumor volumes ofcontrol 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. Oxid Med Cell Longev. 2020 May. Immunol Res. 2019 Jul 10.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Tian S, et al. YN968D1 is a novel and selective inhibitor of vascular endoth