KRN 633 is a cell-permeable, reversible, ATP-competitive VEGFR kinase inhibitor with IC50 of 170 nM, 160 nM, and 125 nM for VEGFR-1, VEGFR-2, VEGFR-3, respectively. It inhibits PDGFR-α and c-Kit at higher concentrations only (IC50 = 0.97 µM and 4.33 µM, respectively) and inactive towards 17 other kinases (IC50 ≥ 10 µM). Shown to suppress VEGF-dependent, but not FGF-dependent, cellular signaling and cell proliferation. Although not cytotoxic to cancer cells, KRN633 exhibits excellent in vivo antitumor activity due to its inhibitory effects on vessel formation and vascular permeability.
| Cell Experiment | |
|---|---|
| Cell lines | A549, Ls174T, DU145, HT29, LNCap and PC-3 cell lines |
| Preparation method | Plating cancer cells in media containig 10% FBS and antibiotics, at densities known to permit exponential growth over the assay period. Culturing the cells for 24 hours before adding KRN633 (0.01 to 10 μM) or just the vehicle (0.1% DMSO in medium) and then growing for a further 96 hours. Using WST-1 reagent to measure cell viability . |
| Concentrations | Dissolved in DMSO, final concentrations 0.01 to 10 μM |
| Incubation time | 96 hours |
| Animal Experiment | |
|---|---|
| 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. |
| Formulation | Suspended in vehicle (0.5% methylcellulose solution) |
| Dosages | 20-100 mg/kg |
| Administration | Gavage once daily |
| Molecular Weight | 416.86 |
| Formula | C20H21ClN4O4 |
| CAS Number | 286370-15-8 |
| Solubility (25°C) | DMSO |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
[3] Akane Morita, et al. Establishment of an abnormal vascular patterning model in the mouse retina
| Related VEGFR/PDGFR Products |
|---|
| Isolinderalactone
Isolinderalactone suppresses human glioblastoma growth and angiogenic activity through the inhibition of VEGFR2 activation in endothelial cells. Isolinderalactone suppressed the expression of B-cell lymphoma 2 (BCL-2), as well as of survivin and X-linked inhibitor of apoptosis protein (XIAP). |
| Oglufanide
Oglufanide (H-Glu-Trp-OH) is a dipeptide immunomodulator isolated from calf thymus. |
| KLTWQELYQLKYKGI
KLTWQELYQLKYKGI (QK) is a VEGF mimicking peptide, binds to the VEGF receptors and competes with VEGF. |
| Protein LMWP
Protein LMWP is a cell-penetrating peptide with vascular endothelial growth factor (VEGF) inhibitory activity. |
| CBO-P11
CBO-P11 specifically binds to receptor of VEGFR-2 and is used as targeting ligand for tumor angiogenesis. |
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2023 AbMole BioScience. All Rights Reserved.
