KRN-633

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Chemical Structure| 286370-15-8 同义名 : -
CAS号 : 286370-15-8
货号 : A263491
分子式 : C20H21ClN4O4
纯度 : 98%
分子量 : 416.86
MDL号 : MFCD14155620
存储条件：

Pure form Inert atmosphere, room temperature

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 25 mg/mL(59.97 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

0.5% methylcellulose+0.2% Tween 80+water 10 mg/mL suspension

生物活性
靶点

  • VEGFR1

    VEGFR1, IC50:170 nM

  • VEGFR3

    VEGFR3, IC50:125 nM

  • VEGFR2

    VEGFR2, IC50:160 nM
描述 The vascular endothelial growth factor (VEGF)-VEGF receptor (R) system is deeply involved in angiogenesis and lymphangiogenesis[3]. KRN-633 inhibits tyrosine phosphorylation of VEGFR-1, VEGFR2, c-Kit, and PDGFR-β (IC50=11.7, 1.16, 8.01, 130 nM) in human umbilical vein endothelial cells. KRN-633 also inhibits the VEGF-driven proliferation of HUVECs (IC50=14.9 nM). KRN-633 suppresses capillary tube formation of endothelial cells. KRN-633 inhibits tumor growth in several tumor xenograft models with diverse tissue origins, including lung, colon, and prostate, in athymic mice and rats. KRN-633 also causes the regression of some well-established tumors and those that have regrown after the cessation of treatment. KRN-633 is well tolerated and has no significant effects on body weight or the general health of the animals. Histologic analysis of tumor xenografts treated with KRN-633 reveals a reduction in the number of endothelial cells in non-necrotic areas and a decrease in vascular permeability[4]. Reduction in the expression levels of VEGF and VEGF receptor-2 in the CL precedes the impairment of luteal circulation and a series of events leading to parturition (i.e., reduction of plasma progesterone, enhancement of myometrium contractility, and onset of parturition). Blocking of VEGF signaling by using the inhibitor of VEGFR tyrosine kinase KRN633 at mid-pregnancy caused a similar sequence of events and induced preterm birth[5]. In retinas of rats injected subcutaneously with KRN633 (10 mg/kg), simplified vasculature attributable to capillary regression and prevention of endothelial cell growth were seen, whereas no visible changes in the morphology of the retinal layers were observed[6].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.40mL

0.48mL

0.24mL

11.99mL

2.40mL

1.20mL

23.99mL

4.80mL

2.40mL
参考文献

[1]Ban HS, Uno M, Nakamura H. Suppression of hypoxia-induced HIF-1alpha accumulation by VEGFR inhibitors: Different profiles of AAL993 versus SU5416 and KRN633. Cancer Lett. 2010 Oct 1;296(1):17-26.

[2]Nakamura K, Yamamoto A, 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.

[3]Masabumi Shibuya. VEGF-VEGFR System as a Target for Suppressing Inflammation and other Diseases. Endocr Metab Immune Disord Drug Targets. 2015;15(2):135-44.

[4]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.

[5]Yoshiko Wada,et al. Role of vascular endothelial growth factor in maintenance of pregnancy in mice. Endocrinology. 2013 Feb;154(2):900-10.

[6]Daiki Asano,et al. Regression of retinal capillaries following N-methyl-D-aspartate-induced neurotoxicity in the neonatal rat retina. J Neurosci Res. 2015 Feb;93(2):380-90.