KRN 633

Catalog No.S1557

For research use only.

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.

KRN 633 Chemical Structure

CAS No. 286370-15-8

Selleck's KRN 633 has been cited by 6 Publications

1 Customer Review

Purity & Quality Control

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Biological Activity

Description 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.
Targets
VEGFR3 [1] VEGFR2 [1] VEGFR1 [1] PDGFRα [1] c-Kit [1] Click to View More Targets
125 nM 160 nM 170 nM 965 nM 4330 nM
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]

Protocol (from reference)

Kinase Assay:[1]
  • 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.

Cell Research:[1]
  • Cell lines: A549, Ls174T, DU145, HT29, LNCap and PC-3 cell lines
  • Concentrations: Dissolved in DMSO, final concentrations 0.01 to 10 μM
  • Incubation Time: 96 hours
  • Method: 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.
Animal Research:[1]
  • Animal Models: 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.
  • Dosages: 20-100 mg/kg
  • Administration: Gavage once daily

Solubility (25°C)

In vitro

DMSO 9 mg/mL
(21.58 mM)
Water Insoluble
Ethanol Insoluble

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
0.5% methylcellulose+0.2% Tween 80
For best results, use promptly after mixing.

10 mg/mL

Chemical Information

Molecular Weight 416.86
Formula

C20H21ClN4O4

CAS No. 286370-15-8
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CCCNC(=O)NC1=C(C=C(C=C1)OC2=NC=NC3=CC(=C(C=C32)OC)OC)Cl

In vivo Formulation Calculator (Clear solution)

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Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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