KRN-633

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 Search

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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15634658
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.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Vascular endothelial growth factor receptor 1 41 Target ID: CHEMBL1868 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15634658	Inhibitor 8297	170.0 nM [IC50]
Vascular endothelial growth factor receptor 2 104 Target ID: CHEMBL279 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15634658	Inhibitor 8297	160.0 nM [IC50]
Vascular endothelial growth factor receptor 3 41 Target ID: CHEMBL1955 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15634658	Inhibitor 8297	125.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cancer 592 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15634658 https://www.ncbi.nlm.nih.gov/pubmed/16432165	Primary		Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
2.29 μg/mL/(mg dose/kg) EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16432165	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15634658	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

Value	Dose	Co-administered	Analyte	Population
25.4 μg × h/mL/(mg dose/kg) EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16432165	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15634658	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
7.93 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16432165	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15634658	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

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P002WDO	https://www.1pchem.com/search?query=1P002WDO
AChemBlock	M15307	http://www.achemblock.com/catalogsearch/result/?q=M15307
AK Scientific	X7494	https://aksci.com/item_detail.php?cat=X7494
Angene	AGN-PC-0WH9OT	http://www.angenechemical.com/productshow/AGN-PC-0WH9OT.html
ApexBio Technology	A5760	https://www.apexbt.com/catalogsearch/result/?q=A5760
AstaTech	FD7289	http://astatechinc.com/CPSResult.php?CRNO=FD7289
BLD Pharm	BD304694	http://www.bldpharm.com/search/Search.html?keyword=BD304694
Cayman Chemical	14871	http://www.caymanchem.com/app/template/Product.vm/catalog/14871
Chem Scene	CS-0220	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0220
ChemShuttle	113672	https://www.chemshuttle.com/catalogsearch/result/?q=113672
Combi-Blocks	QC-1558	http://www.combi-blocks.com/cgi-bin/find.cgi?QC-1558
Debye Scientific	DA-33447	https://www.debyesci.com/index.php?id=product&ext[cno]=DA-33447
Excenen	EX-A2087	http://www.excenen.com/searchresultlist.php?id=EX-A2087
Hairui	HR141546	http://www.hairuichem.com/en/product/search.do?q=HR141546
KeyOrganics	AS-73029	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-73029
Matrix Scientific	147773	http://www.matrixscientific.com/147773.html
MedChem Express	HY-12060	https://www.medchemexpress.com/search.html?q=HY-12060&ft=&fa=&fp=
MolPort	MolPort-016-633-236	https://www.molport.com/shop/molecule-link/MolPort-016-633-236
Molnova	M18365	https://www.molnova.com/en/serch-list.html?keywords=M18365
MuseChem	I002976	https://www.musechem.com/product/I002976.html
ShangHai Biochempartner	BCP23436	http://www.biochempartner.com/search_BCP23436
TargetMol	T6137	https://www.targetmol.com/search?keyword=T6137
eMolecules	11326025	https://orderbb.emolecules.com/search/#?query=11326025
eNovation Chemicals	K09862	https://www.enovationchem.com/Products.asp?SEARCHTEXT=K09862&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-5329549597	https://mcule.com/MCULE-5329549597/

PubMed

Title	Date	PubMed
KRN633: A selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase that suppresses tumor angiogenesis and growth.	2004 Dec	15634658
Suppression of hypoxia-induced HIF-1alpha accumulation by VEGFR inhibitors: Different profiles of AAL993 versus SU5416 and KRN633.	2010 Oct 1	20378243
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	24462631

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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