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
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)
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 |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/15634658Curator's Comment: Description was created based on several sources, including
http://adisinsight.springer.com/drugs/800017407
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 | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL1868 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15634658 |
170.0 nM [IC50] | ||
Target ID: CHEMBL279 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15634658 |
160.0 nM [IC50] | ||
Target ID: CHEMBL1955 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15634658 |
125.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
Cmax
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 |
T1/2
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 |
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 |
|
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 |
|
Effects of KRN633, an inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase, on vascular development of placenta and fetus of mid-pregnancy in mice. | 2010 |
|
Suppression of hypoxia-induced HIF-1alpha accumulation by VEGFR inhibitors: Different profiles of AAL993 versus SU5416 and KRN633. | 2010 Oct 1 |
|
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 |
|
Short-term treatment with VEGF receptor inhibitors induces retinopathy of prematurity-like abnormal vascular growth in neonatal rats. | 2016 Feb |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15634658
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15634658
30-100 nM KRN633 can block survival signaling by VEGF and trigger the apoptosis of HUVECs
Substance Class |
Chemical
Created
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admin
on
Edited
Sat Dec 16 09:27:41 GMT 2023
by
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on
Sat Dec 16 09:27:41 GMT 2023
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Record UNII |
E1V875I8DX
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Record Status |
Validated (UNII)
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Record Version |
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286370-15-8
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CHEMBL406381
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9549295
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DTXSID60429551
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E1V875I8DX
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admin on Sat Dec 16 09:27:42 GMT 2023 , Edited by admin on Sat Dec 16 09:27:42 GMT 2023
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ACTIVE MOIETY |