BMS-690514

EGFR (IC50 = 5 nM); HER2 (IC50 = 20 nM); HER4 (IC50 = 60 nM)

BMS-690514 控制的主要信号陷阱包括生长因子受体 (HER)/ErbB 的人体参与、通过 VEGFR2 的血管生成信号传导、通过 VEGFR3 的淋巴管生成，并且还被证明可以靶向 VEGFR1、Flt-3 和 Lck 。 -690514 具有中等潜力成为 P-gp 底物，并且在 Caco-2 细胞中具有中等范围的渗透性 [2]。 BMS-690514 抑制 VEGFR 家族成员，IC50 值范围为 25 至 50 nM。 BMS-690514 抑制外显子 19 输出的 NSCLC 癌症（HCC4006、HCC827 和 PC9）的增殖，IC50 值范围为 2 至 35 nM。这些肿瘤对这种药物特别敏感。此外，EGFR 阳性肿瘤细胞系（DiFi、NCI-H2073、A431）对 BMS-690514 表现出强烈的敏感性。研究还表明，依赖 HER2 信号传导的肿瘤细胞系对 BMS-690514 极其敏感。 BMS-690514 表现出显着程度的 HER2 基因敏感性。 BMS-690514 的 IC50 值范围为 20 至 60 nM，对乳腺癌和腺癌细胞系 N87、SNU-216、AU565、BT474、KPL4 和 HCC202 有影响 [1]。

已证明 BMS-690514 在多种异种肿瘤移植中效果良好。在动物模型中，BMS-690514 能有效且耐受性良好地抑制肿瘤细胞增殖和肿瘤血流 [1]。研究发现，BMS-690514 在小鼠中的生物利用度为 78%，在比重中为 100%，在猴子中为 8%，在狗中为 29%。 BMS-690514 可以以一个脑宽度的比例穿过血脑屏障。 -690514 的临床前 ADME 特征显示出良好的人体伤口生物利用度，并支持氧化和甲醛途径等途径 [2]。

Rats: Male Sprague-Dawley rats receive BMS-690514 orally by gavage (10 mg/kg) or intraarterially (IA) for 10 minutes. The vehicles used for dosing are PO, PEG400/10mM acetate buffer (pH 5.0, 2 mL/kg) (10:90) and IA, 10mM acetate buffer (pH 5.0, 1 mL/kg). Predose, at 0.17 (or 0.25 for PO), 0.5, 0.75, 1, 2, 4, 6, 8, 12, and 24 hours after the dose are the times at which serial plasma samples are taken. Rats are given an overnight fast and fed four hours after the dose. In a 2-week toxicology study, the brain uptake of BMS-690514 (3, 10, and 30 mg/kg/day) is examined following the final dosage. Three volumes of ice-cooled water are used to weigh and homogenize brain samples. LC/MS/MS is used to determine the concentrations of BMS-690514 in brain homogenates and plasma[2].
Mice: Male balb-c mice are used to study the pharmacokinetics of BMS-690514. 18 mice in total are split into two groups and given either a single IV bolus dose of 1 mg/kg or an oral gavage dose of 5 mg/kg of BMS-690514. The vehicle used is Tween-80/PG/water (10:40:50) for both IV (0.1 mL/mouse) and PO (0.2 mL/mouse) doses. Blood levels of BMS-690514 are assessed at 0.05 (or 0.25 in the case of PO), 0.5, 1, 3, 6, 8, and 24 hours after the dosage. The mice are given their dose six hours after fasting through the night. Each mouse has three blood samples obtained through retro-orbital bleeding, with three mice per time point. For each of the three mice, only one sample is collected at the 24-hour mark. For pharmacokinetic analysis, composite serum concentration–time profiles are created[2].

[1]. Antitumor and antiangiogenic activities of BMS-690514, an inhibitor of human EGF and VEGF receptor kinase families. Clin Cancer Res. 2011 Jun 15;17(12):4031-41.

[2]. Preclinical pharmacokinetics and in vitro metabolism of BMS-690514, a potent inhibitor of EGFR and VEGFR2. J Pharm Sci. 2010 Aug;99(8):3579-93.

BMS-690514 has been investigated for the treatment of Breast Cancer.
Pan HER/VEGFR2 Receptor Tyrosine Kinase Inhibitor BMS-690514 is a pyrrolotriazine-based compound and a pan inhibitor of receptor tyrosine kinases with potential antineoplastic activity. Pan HER/VEGFR2 receptor tyrosine kinase inhibitor BMS-690514 binds to human epidermal growth factor receptors (EGFR) 1, 2 and 4 (HER1, HER2 and HER4) and vascular endothelial growth factor receptor 1, 2 and 3 (VEGFR-1, -2 and -3), all of which are frequently overexpressed by a variety of tumor types. Binding of this agent to these receptors may result in the inhibition of tumor cell proliferation; the inhibition of endothelial cell migration and proliferation and angiogenesis; and tumor cell death.

C19H24N6O2

368.43

368.196

C, 61.94; H, 6.57; N, 22.81; O, 8.69

859853-30-8

859853-30-8

11349170

White to off-white solid powder

1.4±0.1 g/cm3

1.705

-0.52

100.94

3

7

5

27

483

2

C(N1CC[C@@H](N)[C@H](O)C1)C1C=CN2C=1C(=NC=N2)NC1C=CC=C(OC)C=1

CSGQVNMSRKWUSH-IAGOWNOFSA-N

InChI=1S/C19H24N6O2/c1-27-15-4-2-3-14(9-15)23-19-18-13(5-8-25(18)22-12-21-19)10-24-7-6-16(20)17(26)11-24/h2-5,8-9,12,16-17,26H,6-7,10-11,20H2,1H3,(H,21,22,23)/t16-,17-/m1/s1

(3R,4R)-4-amino-1-[[4-(3-methoxyanilino)pyrrolo[2,1-f][1,2,4]triazin-5-yl]methyl]piperidin-3-ol

BMS690514; BMS 690514; BMS-690514

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: ≥ 25 mg/mL (~67.9 mM)

配方 1 中的溶解度: ≥ 2.5 mg/mL (6.79 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

---

配方 2 中的溶解度: ≥ 2.5 mg/mL (6.79 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

---

View More

配方 3 中的溶解度: ≥ 2.5 mg/mL (6.79 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

---

请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。