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Details

Stereochemistry ACHIRAL
Molecular Formula C20H21ClN4O4
Molecular Weight 416.858
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of KRN-633

SMILES

CCCNC(=O)NC1=CC=C(OC2=C3C=C(OC)C(OC)=CC3=NC=N2)C=C1Cl

InChI

InChIKey=VPBYZLCHOKSGRX-UHFFFAOYSA-N
InChI=1S/C20H21ClN4O4/c1-4-7-22-20(26)25-15-6-5-12(8-14(15)21)29-19-13-9-17(27-2)18(28-3)10-16(13)23-11-24-19/h5-6,8-11H,4,7H2,1-3H3,(H2,22,25,26)

HIDE SMILES / InChI

Molecular Formula C20H21ClN4O4
Molecular Weight 416.858
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800017407

KRN633 is a selective inhibitor of Vascular endothelial growth factor receptors VEGFR-1, -2, and -3. KRN633 also blocked the activation of mitogen-activated protein kinases by VEGF, along with human umbilical vein endothelial cell proliferation and tube formation. KRN633 inhibited tumor growth in several in vivo tumor xenograft models with diverse tissue origins, including lung, colon, and prostate, in athymic mice and rats. Kirin Brewery developed angiogenesis inhibitor KRN 633 as a treatment for solid tumours. It is in phase I clinical trials.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2.29 μg/mL/(mg dose/kg)
3 mg/kg single, oral
dose: 3 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
KRN-633 plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
899 ng/mL
20 mg/kg single, oral
dose: 20 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
KRN-633 plasma
Mus musculus
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
25.4 μg × h/mL/(mg dose/kg)
3 mg/kg single, oral
dose: 3 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
KRN-633 plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
7800 ng × h/mL
20 mg/kg single, oral
dose: 20 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
KRN-633 plasma
Mus musculus
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
7.93 h
3 mg/kg single, oral
dose: 3 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
KRN-633 plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
2.24 h
20 mg/kg single, oral
dose: 20 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
KRN-633 plasma
Mus musculus
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
KRN633: A selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase that suppresses tumor angiogenesis and growth.
2004 Dec
Improvement by solid dispersion of the bioavailability of KRN633, a selective inhibitor of VEGF receptor-2 tyrosine kinase, and identification of its potential therapeutic window.
2006 Jan
Suppression of hypoxia-induced HIF-1alpha accumulation by VEGFR inhibitors: Different profiles of AAL993 versus SU5416 and KRN633.
2010 Oct 1
KRN633, an inhibitor of vascular endothelial growth factor receptor tyrosine kinase, induces intrauterine growth restriction in mice.
2013 Aug
Role of vascular endothelial growth factor in maintenance of pregnancy in mice.
2013 Feb
Effects of mTOR inhibition on normal retinal vascular development in the mouse.
2014 Dec
Effects of pre- and post-natal treatment with KRN633, an inhibitor of vascular endothelial growth factor receptor tyrosine kinase, on retinal vascular development and patterning in mice.
2014 Mar
Regression of retinal capillaries following N-methyl-D-aspartate-induced neurotoxicity in the neonatal rat retina.
2015 Feb
Short-term treatment with VEGF receptor inhibitors induces retinopathy of prematurity-like abnormal vascular growth in neonatal rats.
2016 Feb
Patents

Patents

Sample Use Guides

In standard xenograft models, once-daily administration of KRN633 produced >50% tumor growth inhibition in LC-6-LCK, HT29, Ls174T, and LNCap cells, and slight regression of A549 tumors at 100 mg/kg/d
Route of Administration: Oral
30-100 nM KRN633 can block survival signaling by VEGF and trigger the apoptosis of HUVECs
Substance Class Chemical
Created
by admin
on Sat Dec 16 09:27:41 GMT 2023
Edited
by admin
on Sat Dec 16 09:27:41 GMT 2023
Record UNII
E1V875I8DX
Record Status Validated (UNII)
Record Version
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Name Type Language
KRN-633
Common Name English
VEGF RECEPTOR TYROSINE KINASE INHIBITOR III
Common Name English
UREA, N-(2-CHLORO-4-((6,7-DIMETHOXY-4-QUINAZOLINYL)OXY)PHENYL)-N'-PROPYL-
Systematic Name English
N-(2-CHLORO-4-((6,7-DIMETHOXY-4-QUINAZOLINYL)OXY)PHENYL)-N'-PROPYLUREA
Systematic Name English
KRN633
Code English
K00589A
Code English
Code System Code Type Description
CAS
286370-15-8
Created by admin on Sat Dec 16 09:27:42 GMT 2023 , Edited by admin on Sat Dec 16 09:27:42 GMT 2023
PRIMARY
ChEMBL
CHEMBL406381
Created by admin on Sat Dec 16 09:27:42 GMT 2023 , Edited by admin on Sat Dec 16 09:27:42 GMT 2023
PRIMARY
PUBCHEM
9549295
Created by admin on Sat Dec 16 09:27:42 GMT 2023 , Edited by admin on Sat Dec 16 09:27:42 GMT 2023
PRIMARY
EPA CompTox
DTXSID60429551
Created by admin on Sat Dec 16 09:27:42 GMT 2023 , Edited by admin on Sat Dec 16 09:27:42 GMT 2023
PRIMARY
FDA UNII
E1V875I8DX
Created by admin on Sat Dec 16 09:27:42 GMT 2023 , Edited by admin on Sat Dec 16 09:27:42 GMT 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
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ACTIVE MOIETY