KRN-633

Names

[ Name ]:
KRN-633

[Synonym ]:
N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]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-
1-(2-chloro-4-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-propylurea
1-{2-chloro-4-[(6,7-dimethoxyquinazolin-4-yl)oxy]phenyl}-3-propylurea
KRN633,KRN-633,KRN 633
S1557_Selleck
1-{2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-3-propylurea
KRN633
VEGF Receptor Tyrosine Kinase Inhibitor III,KRN633
KRN 633
KRN-633

Biological Activity

[Description]:

KRN-633 is a potent VEGFR inhibitor with IC50s of 170, 160 and 125 nM for VEGFR1, VEGFR2 and VEGFR3, respectively.

[Related Catalog]:

Research Areas >> Cancer

[Target]

VEGFR1:170 nM (IC50)

VEGFR2:160 nM (IC50)

VEGFR3:125 nM (IC50)

[In Vitro]

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[1].

[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].

[Kinase Assay]

Cell-free kinase assays are done to obtain IC50 values against a variety of recombinant receptor and non-RTKs. KRN-633 is tested from 0.3 nM to 10 μM. All assays are done in quadruplicate with 1 μM ATP[1].

[Cell Assay]

A549, Ls174T, HT29, DU145, LNCap, and PC-3 cells cancer cells are cultured for 24 hours before adding KRN-633 (0.01 to 10 μM) or vehicle (0.1% DMSO in medium) and then grow for a further 96 hours. Cell viability is measured using WST-1 reagent. The percentage viability is determined relative to the untreated control[1].

[Animal admin]

Rats: Human tumor xenografts are established in the hind flank of athymic rats (BALB/cA, Jcl-nu). Rats are randomized into groups of five at the point when the tumors reach the average size indicated (162 to 657 mm3) and are then treated with KRN-633 or vehicle, either once (qd) or twice (bid) per day, at the dosages shown. The percentage of tumor growth inhibition compared with the vehicle-treated group is calculated on the day after the last treatment (day 14)[1]. Mice: The mice are randomized into groups of five at the point when the tumors reached the average sizes: 103 to 260 mm3 or 500 to 667 mm3. They are then treated with KRN-633 or vehicle, either once (qd) or twice (bid) per day, at the dosages of 10-100 mg/kg. The percentage of tumor growth inhibition (TGI) compared with the vehicle-treated group is calculated on the day after the last treatment[1].

[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 Dec;3(12):1639-49.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.3±0.1 g/cm3

[ Boiling Point ]:
545.6±50.0 °C at 760 mmHg

[ Melting Point ]:
229 °C

[ Molecular Formula ]:
C₂₀H₂₁ClN₄O₄

[ Molecular Weight ]:
416.858

[ Flash Point ]:
283.7±30.1 °C

[ Exact Mass ]:
416.125122

[ PSA ]:
98.09000

[ LogP ]:
4.14

[ Appearance of Characters ]:
white to beige

[ Vapour Pressure ]:
0.0±1.5 mmHg at 25°C

[ Index of Refraction ]:
1.629

[ Storage condition ]:
?20°C

[ Water Solubility ]:
DMSO: soluble3mg/mL, clear (warmed)

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302

[ Hazard Codes ]:
Xn

[ Risk Phrases ]:
22

[ RIDADR ]:
NONH for all modes of transport

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Related Compounds

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