苹果酸苏尼替尼 标准品
| EC | EINECS 638-825-9 |
| MDL | MFCD08282795 |
| 别名 | 苹果酸苏尼替尼;苹果酸舒尼替尼盐;sunitynib L-malate; |
| 英文名称 | Sunitinib Malate |
| CAS | 341031-54-7 |
| 分子式 | C22H27FN4O2·C4H6O5 |
| 分子量 | 532.56 |
| 储存条件 | -20℃ |
| 纯度 | HPLC≥97% |
| 外观（性状） | White to orange Powder |
| 单位 | 瓶 |
| 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 |
| 规格 | 50mg |
苹果酸卡博替尼
| 有效期 | 2年 |
| 描述 | 是一种有效的多受体酪氨酸激酶抑制剂， 抑制VEGFR2，c-Met，Kit，Axl 和 Flt3。 |
| EC | EINECS 691-711-0 |
| MDL | MFCD20923480 |
| 别名 | XL-184;卡博替尼苹果酸盐 |
| 英文名称 | Cabozantinib Malate |
| CAS | 1140909-48-3 |
| 分子式 | C28H24FN3O5·C4H6O5 |
| 分子量 | 635.59 |
| 储存条件 | RT |
| 纯度 | ≥98% |
| 外观（性状） | Solid |
| 单位 | 瓶 |
| 生物活性 | Cabozantinib (S-malate)是一种有效的多受体酪氨酸激酶抑制剂， 抑制VEGFR2，c-Met，Kit，Axl 和 Flt3 的 IC50 分别为0.035，1.3，4.6，7 和 11.3 nM。[1-3] |
| In Vitro | XL184（0.1-0.5μM）抑制所有MPNST细胞中的组成型和诱导型MET磷酸化及其产生的下游信号传导。 XL184（>0.1μM）引起显著的MPNST细胞生长抑制;需要更高的XL184剂量来抑制NSC生长。 XL184处理阻断HGF诱导的MPNST运动和侵袭（在NSC上发现的类似作用）[2]。在细胞试验中，cabozantinib抑制MET和VEGFR2以及KIT，FLT3和AXL的磷酸化，IC50值分别为7.8,1.9,5.0,7.5和42μM。 Cabozantinib还响应来自MDA-MB-231（IC50 = 5.1 nM），A431（IC50 = 4.1 nM），HT1080（IC50 = 7.7 nM）和B16F10（IC50 = 4.7 nM）培养物的条件培养基抑制小管形成细胞[3]。 |
| In Vivo | 卡博替尼（60mg / kg，ip）降低肿瘤血管分布，在动物中降低范围从3mg / kg的67％至30mg / kg的83％。与载体的相应值[1]相比，在10周龄开始治疗7天的RIP-Tag2小鼠中的肿瘤在XL880后小40％，在XL184后小35％。 XL184（30 mg / kg）显著降低小鼠的微血管密度[2]。卡博替尼（100mg / kg，口服）抑制体内刺激肝脏肝细胞中HGF的MET磷酸化和VEGF刺激的FLK1磷酸化，同时抑制持续8小时后的两种靶标。卡博替尼（100mg / kg，口服）破坏肿瘤血管系统并促进肿瘤和内皮细胞死亡。 Cabozantinib（1-60 mg / kg，po）抑制肿瘤生长并促进体内肿瘤消退[3]。 |
| 激酶实验 | 使用荧光素酶偶联的化学发光，33P-磷酰基转移或AlphaScreen技术测定卡博替尼对270种人激酶的广泛组的抑制特性。使用重组人全长，谷胱甘肽S-转移酶标签或组氨酸标签融合蛋白，并通过测量在ATP浓度等于或低于该浓度的肽底物聚（Glu，Tyr）的磷酸化来确定半数最大抑制浓度（IC50）值。每种激酶的Km。通过测定ATP浓度范围内的IC 50值，使用AlphaScreen Assay评估激酶抑制的机制。 |
| SMILES | O=C([C@H](CC(O)=O)O)O.O=C(NC1=CC=C(C=C1)OC2=CC=NC3=CC(OC)=C(C=C23)OC)C4(CC4)C(NC5=CC=C(C=C5)F)=O |
| 靶点 | VEGFR |
| 动物实验 | 将H441细胞（3×106）皮内植入后腹部，当肿瘤达到约150mg时，使用下式计算肿瘤重量:(肿瘤体积=长度（mm）×宽度2（mm2）] / 2，小鼠随机分组（每组n = 5）并口服单剂量100mg / kg剂量的cabozantinib或载体。在指定的时间点收集肿瘤。用抗MET（SC161）对合并的肿瘤裂解物进行免疫沉淀，并用抗蛋白质印迹法进行免疫沉淀。 -phosphotyrosine MET（pY1230 / 34/35）。在印迹剥离后，将总MET定量为上样对照。在单独的实验中，给予幼稚小鼠（每组n = 5）单次100mg / kg剂量的cabozantinib或在收集肝脏前10分钟静脉注射HGF（每只小鼠10μg），肝脏裂解液中的MET磷酸化分析如上所述。在另一项实验中，幼稚小鼠（每组n = 5）给予单一100 mg / kg剂量的cabozantinib或载体，然后在肺采集前30分钟静脉内施用VEGF（每只小鼠10μg）。汇集的肺裂解物用FLK1（SC6251）进行免疫沉淀，并用抗磷酸酪氨酸（4G10）进行蛋白质印迹。印迹剥离后，定量总FLK1作为上样对照。 |
| 细胞实验 | 将细胞在含有10％FBS的培养基中一式三份接种过夜。第二天，用连续稀释的卡博替尼处理细胞48小时，然后使用细胞增殖ELISA，BrdUrd分析增殖。 |
| 数据来源文献 | [1]. You WK, et al. VEGF and c-Met blockade amplify angiogenesis inhibition in pancreatic islet cancer. Cancer Res, 2011, 71(14), 4758-4768.
[2]. Torres KE, et al. Activated MET is a molecular prognosticator and potential therapeutic target for malignant peripheral nerve sheath tumors. Clin Cancer Res, 2011, 17(12), 3943-3955. [3]. Yakes FM, et al. Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther, 2011, 10(12), 2298-2308 |
| 规格 | 5mg 10mg 20mg |
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。
苹果酸脱氢酶
| 有效期 | 2年 |
| 级别 | Ultra Pure Grade |
| 别名 | Malate dehydrogenase porcine heart；L-malate: NAD+oxidoreductase, mitochondrial malate dehydrogenase；MDH |
| 英文名称 | Malatedehydrogenase |
| CAS | 9001-64-3 |
| 分子量 | 70 kDa |
| 储存条件 | 2-8℃ |
| 酶活/效价 | 30.4KU/ML |
| 外观（性状） | 混浊液体 |
| 单位 | 支 |
| 规格 | 5KU |
苹果酸脱氢酶是细胞溶酶体中的一种氧化还原酶。
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D-(+)-苹果酸 标准品
| EC | EINECS 211-262-2 |
| MDL | MFCD00004245 |
| 别名 | (R)-malic acid;D(+)-苹果酸;(R)-羟基丁二酸;D-苹果酸; |
| 英文名称 | D-(+)-Malic Acid |
| CAS | 636-61-3 |
| 分子式 | C4H6O5 |
| 分子量 | 134.09 |
| 储存条件 | 2-8℃ |
| 纯度 | GC≥98% |
| 外观（性状） | Off-white Powder |
| 单位 | 支 |
| SMILES | O=C(O)[C@H](O)CC(O)=O |
| 规格 | 100mg |