KRN 633
(Synonyms: N-[2-氯-4-[(6,7-二甲氧基-4-喹唑啉基)氧基]苯基]-N'-丙基脲) 目录号 : GC12590
A VEGF receptor tyrosine kinase inhibitor
Cas No.:286370-15-8
Sample solution is provided at 25 µL, 10mM.
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KRN 633 is a selective inhibitor of VEGFR-1, VEGFR-2 and VEGFR-3 with IC50 value of 170 nM, 160 nM and 125 nM [1].
Vascular endothelial growth factor receptor (VEGFR) is a protein and plays an important role in tumor angiogenesis by cooperating with its ligand VEGF [1].
KRN 633 is a potent VEGFR inhibitor. When tested with HUVECs, KRN 633 inhibited the cell proliferation that mediated by VEGF with the IC50 value of 14.9 nmol/L and suppressed the capillary tube formation by ~50% at the dose of 10 nmol/L [1].
In mid-pregnant mice model, KRN633 was used at the dose of 5 mg/kg once daily from embryonic day 13.5 until the day of delivery and the effect on vascular growth was slightly delayed on postnatal day 4 (P4) and on P8 it was observed that KRN633 resulted in the decreased numbers of central arteries and veins and abnormal branching of the central arteries [2]. When tested with athymic mouse xenograft HT29 cells model, administration of KRN633 inhibited tumor growth as ~90% from the initial tumor volume rangs from 500-667 mm3, while had less effect Du145 xenograft mouse models by inhibiting tumor angiogenesis and vascular permeability [1].
References:
[1]. Nakamura, K., et al., KRN633: A selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase that suppresses tumor angiogenesis and growth. Mol Cancer Ther, 2004. 3(12): p. 1639-49.
[2]. Morita, A., et al., Treatment of mid-pregnant mice with KRN633, an inhibitor of vascular endothelial growth factor receptor tyrosine kinase, induces abnormal retinal vascular patterning in their newborn pups. Birth Defects Res B Dev Reprod Toxicol, 2014. 101(4): p. 293-9.
Kinase experiment: | Cell-free kinase assays are done to obtain IC50 values against a variety of recombinant receptor and non-RTKs. KRN-633 is tested from 0.3 nM to 10 μM. All assays are done in quadruplicate with 1 μM ATP[1]. |
Cell experiment: | A549, Ls174T, HT29, DU145, LNCap, and PC-3 cells cancer cells are cultured for 24 hours before adding KRN-633 (0.01 to 10 μM) or vehicle (0.1% DMSO in medium) and then grow for a further 96 hours. Cell viability is measured using WST-1 reagent. The percentage viability is determined relative to the untreated control[1]. |
Animal experiment: | Rats: Human tumor xenografts are established in the hind flank of athymic rats (BALB/cA, Jcl-nu). Rats are randomized into groups of five at the point when the tumors reach the average size indicated (162 to 657 mm3) and are then treated with KRN-633 or vehicle, either once (qd) or twice (bid) per day, at the dosages shown. The percentage of tumor growth inhibition compared with the vehicle-treated group is calculated on the day after the last treatment (day 14)[1]. Mice: The mice are randomized into groups of five at the point when the tumors reached the average sizes: 103 to 260 mm3 or 500 to 667 mm3. They are then treated with KRN-633 or vehicle, either once (qd) or twice (bid) per day, at the dosages of 10-100 mg/kg. The percentage of tumor growth inhibition (TGI) compared with the vehicle-treated group is calculated on the day after the last treatment[1]. |
References: [1]. Nakamura K, et al. KRN633: A selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase that suppresses tumor angiogenesis and growth. Mol Cancer Ther. 2004 Dec;3(12):1639-49. | |
| Cas No. | 286370-15-8 | SDF | |
| 别名 | N-[2-氯-4-[(6,7-二甲氧基-4-喹唑啉基)氧基]苯基]-N'-丙基脲 | ||
| 化学名 | 1-[2-chloro-4-(6,7-dimethoxyquinazolin-4-yl)oxyphenyl]-3-propylurea | ||
| Canonical SMILES | CCCNC(=O)NC1=C(C=C(C=C1)OC2=NC=NC3=CC(=C(C=C32)OC)OC)Cl | ||
| 分子式 | C20H21ClN4O4 | 分子量 | 416.86 |
| 溶解度 | ≥ 13.75mg/mL in DMSO with gentle warming | 储存条件 | Store at -20°C |
| General tips | 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；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3989 mL | 11.9944 mL | 23.9889 mL |
| 5 mM | 0.4798 mL | 2.3989 mL | 4.7978 mL |
| 10 mM | 0.2399 mL | 1.1994 mL | 2.3989 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >99.00%
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