KRN633

Cas No.:	286370-15-8
Chemical Name:	VEGF receptor tyrosine kinase inhibitor III
Synonyms:	KRN 633;1-[2-chloro-4-(6,7-dimethoxyquinazolin-4-yl)oxyphenyl]-3-propylurea;1-(2-chloro-4-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-propylurea;KRN633,KRN-633,KRN 633;N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N'-propylurea;VEGF Receptor Tyrosine Kinase Inhibitor III,KRN633;KRN-633;N-[2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl]-N′-propyl-urea;N-[2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl]-N'-propylurea;KRN633;K00589a;VEGF receptor tyrosine kinase inhibitor III;E1V875I8DX;1-{2-chloro-4-[(6,7-dimethoxyquinazolin-4-yl)oxy]phenyl}-3-propylurea;AK174947;N-(2-chloro-4-((6,7-dimethoxy-4-quinazolinyl)oxy)phenyl)-N'-propylurea;1-(2-chloro-4-((6,7-dimethoxyquinazolin-4-yl)oxy)phenyl)-3-propylurea;Urea, N-(2-chl
SMILES:	ClC1C([H])=C(C([H])=C([H])C=1N([H])C(N([H])C([H])([H])C([H])([H])C([H])([H])[H])=O)OC1C2=C([H])C(=C(C([H])=C2N=C([H])N=1)OC([H])([H])[H])OC([H])([H])[H]
Formula:	C20H21ClN4O4
M.Wt:	416.8581
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

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