KRN 633

製品コードS1557 バッチS155702

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C20H21ClN4O4
分子量 416.86 CAS No. 286370-15-8
Solubility (25°C)* 体外 DMSO 9 mg/mL (21.58 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
0.5% methylcellulose 0.2% Tween 80
10.0mg/ml Taking the 1 mL working solution as an example, take 10 mg of this product, add it to 1 ml of 0.5% methylcellulose+0.2% Tween 80 clear solution, and mix evenly to make it a uniform suspension. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 KRN 633 is an ATP-competitive inhibitor of VEGFR1/2/3 with IC50 of 170 nM/160 nM/125 nM, weakly inhibits PDGFR-α/β and c-Kit, does not block the phosphorylation of FGFR-1, EGFR or c-Met in cell.
in vitro KRN 633, a novel quinazoline urea derivative, strongly inhibits VEGFR1, VEGFR2 and VEGFR3 receptors with IC50 values of 170 nM, 160 nM and 125 nM respectively. It shows lower inhibitory activity towards non-RTKs, such as PDGF receptor (PDGFRα and β, c-Kit, breast tumor kinase, and tunica interna endothelial cell kinase tyrosine kinases (IC50 = 965, 9850, 4330, 9200, and 9900 nM, respectively). KRN 633 potently inhibits ligand VEGF induced phosphorylation of VEGFR2 in HUVECs with an IC50 of 1.16 nM. KRN 633 also inhibits VEGF-dependent, but not bFGF-dependent, phosphorylation of the MAP kinases in endothelial cells, with IC50 values of 3.51 nM and 6.08 nM for ERK1 and ERK2, respectively. KRN633 has also been shown to inhibit the VEGF-driven proliferation of HUVECs with an IC50 of 14.9 nM, but it only suppresses FGF-driven proliferation at 3 μM weakly. [1] KRN 633 inhibits hypoxia-induced transcriptional activation of HIF-1α in a concentration-dependent manner with an IC50 of 3.79 μM, through the inhibition of both Akt and ERK phosphorylation signaling pathways. [2]
in vivo Although not cytotoxic to various cancer cells in vitro, KRN633 exhibits excellent antitumor activity in vivo due to its inhibitory effect on tumor vessel formation and vascular permeability. Once-daily administration of KRN633 at 100 mg/kg/d produces significant tumor growth inhibition in A549, LC-6-LCK, HT29, Ls174T, LNCap and Du145 cells while twice-daily administration of KRN633 at 100 mg/kg induces ~90% growth inhibition of HT29 tumors. [1] Treatment of mid-pregnancy mice with KRN 633 (300 mg/kg, p.o.) reduces the blood supply to fetal tissues due to diminished vascularization in both placenta and fetal organs and consequently increases the risk of induction of intrauterine growth restriction (IUGR). [3]

プロトコル(参考用のみ)

キナーゼアッセイ Cell-Free Kinase Assays
Cell-free kinase assays are done to obtain IC50 values against a variety of recombinant VEGF receptors. KRN633 is tested at concentrations varying from 0.3 nM to 10 μM. All assays are done in quadruplicate with 1 μM ATP.
細胞アッセイ 細胞株 A549, Ls174T, DU145, HT29, LNCap and PC-3 cell lines
濃度 Dissolved in DMSO, final concentrations 0.01 to 10 μM
反応時間 96 hours
実験の流れ Cancer cells are plated in media containig 10% FBS and antibiotics, at densities known to permit exponential growth over the assay period. The cells are cultured for 24 hours before adding KRN633 (0.01 to 10 μM) or just the vehicle (0.1% DMSO in medium) and then grown for a further 96 hours. Cell viability is measured using WST-1 reagent.
動物実験 動物モデル A549, Ls174T, HT29, DU145, LNCap, PC-3 cells and LC-6-JCK are established in athymic mice (BALB/cA, Jcl-nu) and athymic rats (F344/N, Jcl-rnu), respectively.
投薬量 20-100 mg/kg
投与方法 Gavage once daily

カスタマーフィードバック

Data from [Data independently produced by , , Mol Cells, 2013, 36:347-354.]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

The in vitro effect of VEGF receptor inhibition on primary alveolar osteoblast nodule formation. [ Aust Dent J, 2020, 10.1111/adj.12752] PubMed: 32072641
Regorafenib induces adaptive resistance of colorectal cancer cells via inhibition of vascular endothelial growth factor receptor. [ J Med Invest, 2017, 64(3.4):262-265] PubMed: 28954993
Synergistic effect of therapeutic stem cells expressing cytosine deaminase and interferon-beta via apoptotic pathway in the metastatic mouse model of breast cancer. [ Oncotarget, 2016, 7(5):5985-99] PubMed: 26716512
Deconstructing the Iboga Alkaloid Skeleton: Potentiation of FGF2-induced Glial Cell Line-Derived Neurotrophic Factor Release by a Novel Compound [ ACS Chem Biol, 2016, 11(1):77-87] PubMed: 26517751
Co-treatment with therapeutic neural stem cells expressing carboxyl esterase and CPT-11 inhibit growth of primary and metastatic lung cancers in mice. [ Oncotarget, 2014, 5(24):12835-48] PubMed: 25544747
Anticancer effects of the engineered stem cells transduced with therapeutic genes via a selectivetumor tropism caused by vascular endothelial growth factor toward HeLa cervical cancer cells. [Kim HS, et al. Mol Cells, 2013, 36(4):347-54] PubMed: 24008363

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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