舒尼替尼 标准品
| MDL | MFCD08273555 |
| 别名 | Sutent-d4;SU11248;Sunitinib;Suniti; |
| 英文名称 | Sunitinib |
| CAS | 557795-19-4 |
| 分子式 | C22H27FN4O2 |
| 分子量 | 398.47 |
| 储存条件 | 2-8℃ |
| 纯度 | HPLC≥98% |
| 外观（性状） | powder |
| 单位 | 瓶 |
| SMILES | O=C(NCCN(CC)CC)C1=C(NC(/C=C2C(NC3=C2C=C(C=C3)F)=O)=C1C)C |
| 规格 | 100mg |
苹果酸舒尼替尼
| MDL | MFCD08282795 |
| EC | EINECS 638-825-9 |
| 别名 | 苹果酸苏尼替尼;苹果酸舒尼替尼盐;sunitynibL-malate |
| 英文名称 | Sunitinib Malate |
| CAS | 341031-54-7 |
| 分子式 | C22H27FN4O2·C4H6O5 |
| 分子量 | 532.56 |
| 纯度 | Purity≥99% |
| 单位 | 支 |
| 生物活性 | Sunitinib Malate (formerly also known as SU11248 Malate; trade nameSutent)) is a potent, orally bioavailable and multi-targeted RTK (receptor tyrosine kinase) inhibitor with potent anticancer activities. It inhibits VEGFR2 (Flk-1) and PDGFRβ with IC50s of 80 nM and 2 nM in cell-free assays, and also inhibits c-Kit. It was approved by the FDA for the treatment of renal cell carcinoma and imatinib-resistant gastrointestinal stromal tumor on January 26, 2006. Sunitinib Malate is the malate salt of an indolinone-based tyrosine kinase inhibitor with potential antineoplastic activity. Sunitinib blocks the tyrosine kinase activities of VEGFR2, PDGFRb, and c-kit, thereby inhibiting angiogenesis and cell proliferation. [1] |
| 激酶实验 | IC50 values for Sunitinib against VEGFR2 (Flk-1) and PDGFRβ are determined using glutathione S-transferasefusion proteins containing the complete cytoplasmic domain of the RTK. Biochemical tyrosine kinase assays to quantitate the trans-phosphorylation activity of VEGFR2 (Flk-1) and PDGFRβ are performed in 96-well microtiter plates precoated (20 μg/well in PBS; incubated overnight at 4 °C) with the peptide substrate poly-Glu,Tyr (4:1). Excess protein binding sites are blocked with the addition of 1-5% (w/v) BSA in PBS. Purified GST-fusion proteins are produced in baculovirus-infected insect cells. GST-VEGFR2 and GST-PDGFRβ are then added to the microtiter wells in 2 × concentration kinase dilution buffer consisting of 100 mM HEPES, 50 mM NaCl, 40 μM NaVO4, and 0.02% (w/v) BSA. The final enzyme concentration for GST-VEGFR2 or GST-PDGFRβ is 50 ng/mL. Twenty-five μL of diluted Sunitinib are subsequently added to each reaction well to produce a range of inhibitor concentrations appropriate for each enzyme. The kinase reaction is initiated by the addition of different concentrations of ATP in a solution of MnCl2 so that the final ATP concentrations spanned the Km for the enzyme, and the final concentration of MnCl2 is 10 mM. The plates are incubated for 5-15 minutes at room temperature before stopping the reaction with the addition of EDTA. The plates are then washed three times with TBST. Rabbit polyclonal antiphosphotyrosine antisera are added to the wells at a 1:10,000 dilution in TBST containing 0.5% (w/v) BSA, 0.025% (w/v) nonfat dry milk, and 100 μM NaVO4 and incubated for 1 hour at 37 °C. The plates are then washed three times with TBST, followed by the addition of goat antirabbit antisera conjugated with horseradish peroxidase (1:10,000 dilution in TBST). The plates are incubated for 1 hour at 37 °C and then washed three times with TBST. The amount of phosphotyrosine in each well is quantitated after the addition of 2,2′-azino-di-[3-ethylbenzthiazoline sulfonate] as substrate.[2] |
| SMILES | O=C(NCCN(CC)CC)C1=C(NC(/C=C2C(NC3=C2C=C(C=C3)F)=O)=C1C)C.O=C([C@H](CC(O)=O)O)O |
| 靶点 | PDGFR |
| 数据来源文献 | [1]. J Med Chem. 2003;46(7):1116-9; Clin Cancer Res. 2003;9(1):327-37; Blood. 2003;101(9):3597-605. [2]. Sun L, et al. J Med Chem, 2003, 46(7), 1116-1119. |
| 规格 | 50mg 10mM*1mL in DMSO 100mg 200mg |
Sunitinib Malate是一种有效的酪氨酸激酶抑制剂， 抑制 VEGFR2 和 PDGFRβ。
舒尼替尼
| MDL | MFCD08273555 |
| 别名 | Sutent-d4;SU11248;Sunitinib;Suniti |
| 英文名称 | Sunitinib |
| CAS | 557795-19-4 |
| 分子式 | C22H27FN4O2 |
| 分子量 | 398.47 |
| 纯度 | HPLC≥98% |
| 单位 | 支 |
| 生物活性 | Sunitinib (SU 11248) is a multi-targeted receptor tyrosine kinase inhibitor with IC50s of 80 nM and 2 nM for VEGFR2 and PDGFRβ, respectively[1]. Sunitinib, an ATP-competitive inhibitor, effectively inhibits autophosphorylation of Ire1α by inhibiting autophosphorylation and consequent RNase activation[2]. |
| In Vitro | Sunitinib Malate is also a good inhibitor of KIT and FLT-3[1]. In RS4;11 cells (FLT3-WT), treatment with Sunitinib (SU11248) inhibits FLT3-WT phosphorylation in a dose-dependent manner with IC50 of approximately 250 nM. In MV4;11 cells that express FLT3-ITD, Sunitinib inhibits FLT3-ITD phosphorylation in a dose-dependent manner with an IC50 of 50 nM following a 2-hour treatment[3].In biochemical assays, Sunitinib (SU11248) exhibits competitive inhibition (with regard to ATP) against Flk-1 and PDGFRβ with Ki values of 9 nM and 8 nM, respectively. Sunitinib is also a competitive, albeit less potent, inhibitor of FGFR1 tyrosine kinase activity, with a Ki value of 0.83 μM. In addition to these three structurally related split kinase domain RTKs, the activity of Sunitinib has also been evaluated against a broad panel of additional tyrosine and serine/threonine kinases. In these biochemical assays, the IC50 values for Sunitinib are generally at least 10-fold higher than those for Flk-1 and PDGFR (e.g., IC50values of: >10 μM for EGFR and Cdk2; 4 μM for Met; 2.4 μM for IGFR-1; 0.8 μM for Abl; and 0.6 μM for Src)[4]. |
| In Vivo | Sunitinib Malate has very good oral bioavailability, is highly efficacious in a number of preclinical tumor models, and is well tolerated at efficacious doses[1]. Sunitinib (80 mg/kg/day) inhibits the growth of established SF763T and Colo205 tumor xenografts in athymic mice. Sunitinib (SU11248) treatment effectively inhibits the growth of established tumor xenografts[4]. |
| SMILES | O=C(NCCN(CC)CC)C1=C(NC(/C=C2C(NC3=C2C=C(C=C3)F)=O)=C1C)C |
| 靶点 | VEGFR |
| 动物实验 | Mice[2] Female nu/nu mice (8-12 weeks old, 25 grams) are used. Briefly, 3-5×106 tumor cells are implanted s.c. into the hind flank region of mice on day 0. Daily treatment of tumor-bearing mice with oral administration of Sunitinib as a carboxymethyl cellulose suspension or as a citrate buffered (pH 3.5) solution is initiated once the tumors reached the indicated average size. Tumor growth is evaluated based on twice-weekly measurement of tumor volume. Typically, studies are terminated when tumors in vehicle-treated animals reach an average size of 1000 mm3 or when the tumors are judged to adversely effect the well being of the animals. Rats[4] Adult male Wistar rats (325-349 g) are used. To validate the ability of the time-lapse imaging method to evaluate the anti-angiogenic effects for a given drug treatment, two drug studies are conducted. In the first study, mesenteric windows are harvested from adult male Wistar rats and cultured for 3 days according to the two experimental groups: 1) 10% serum (n=8 tissues from 4 rats), and 2) 10% serum+Sunitinib (5 μM; n=8 tissues from 4 rats). |
| 细胞实验 | RS4;11 and MV4;11 cell lines are starved overnight in medium containing 0.1% FBS prior to addition of Sunitinib (1 nM, 5 nM, 10 nM, 25 nM, 75 nM, 100 nM, 250 nM, 500 nM) and FL (50 ng/mL; FLT3-WT cells only). Proliferation is measured after 48 hours of culture using the Alamar Blue assay in triplicate for each condition, as described by the manufacturer. Trypan blue cell viability assays are performed in parallel and yielded similar results[3]. |
| 数据来源文献 | [1]. Sun L, et al. Discovery of 5-[5-fluoro-2-oxo-1,2- dihydroindol-(3Z)-ylidenemethyl]-2,4- dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide, a novel tyrosine kinase inhibitor targeting vascular endothelial and platelet-derived growth factor receptor tyrosine kinase. J Med Chem. 2003 Mar 27;46(7):1116-9.
[2]. Ali MM, et al. Structure of the Ire1 autophosphorylation complex and implications for the unfolded protein response. EMBO J. 2011 Mar 2;30(5):894-905. [3]. O’Farrell AM, et al. SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood. 2003 May 1;101(9):3597-605. [4]. Mendel DB, et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Can |
| 规格 | 50mg 10mM*1mL in DMSO 100mg 200mg |
是一种多靶点受体酪氨酸激酶抑制剂，抑制VEGFR2 和 PDGFRβ 。
舒尼替尼
| 英文名称 | Sunitinib |
| CAS | 557795-19-4 |
| 储存条件 | 2-8℃ |
| 单位 | 瓶 |
| 规格 | 30mg |