| Identification | Back Directory | [Name]
KRN 633 | [CAS]
286370-15-8 | [Synonyms]
CS-463
KRN 633
KRN 633;KRN-633
KRN 633 USP/EP/BP
KRN633; KRN-633; KRN 633
VEGFR Tyrosine Kinase Inhibitor III, KRN633
KRN 633 (This product is unavailable in the U.S.)
1-(2-chloro-4-(6,7-diMethoxyquinazolin-4-yloxy)phenyl)-3-propylurea
N-[2-Chloro-4-(6,7-dimethoxyquinazolin-4-yloxy)phenyl]-N'-propylurea
N-[2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl]-N'-propylurea
Urea, N-[2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl]-N'-propyl-
N-[2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl]-N'-propylurea KRN633 | [Molecular Formula]
C20H21ClN4O4 | [MDL Number]
MFCD14155620 | [MOL File]
286370-15-8.mol | [Molecular Weight]
416.86 |
| Chemical Properties | Back Directory | [Melting point ]
231-232°C | [Boiling point ]
545.6±50.0 °C(Predicted) | [density ]
1.321 | [storage temp. ]
-20°C | [solubility ]
DMSO: soluble3mg/mL, clear (warmed) | [form ]
powder | [pka]
13.08±0.70(Predicted) | [color ]
white to beige |
| Hazard Information | Back Directory | [Uses]
KRN 633 is an ATP-competitive inhibitor of VEGFR1/2/3 with IC50 of 170 nM/160 nM/125 nM and also inhibits PDGFRα/β with IC50 of 965 nM/9850 nM. | [Biological Activity]
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]. | [Biochem/physiol Actions]
KRN633 is a cell-permeable; reversible and ATP-competitive inhibitor of vascular endothelial growth factor receptor tyrosine kinase (VEGFR) with IC50 values of 170, 160, and 125 nM for VEGFR-1, -2, -3, respectively. Krn633 inhibits PDGFR-α and c-Kit only at higher concentrations (IC50 = 0.97 and 4.33 μM, respectively) and is inactive towards a panel of 17 other kinases (IC50 >/= 10 μM). | [in vivo]
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[1]. | [target]
VEGFR3 | [IC 50]
VEGFR1: 170 nM (IC50); VEGFR2: 160 nM (IC50); VEGFR3: 125 nM (IC50) | [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. |
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