Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C23H23N7O3 |
| Molecular Weight | 445.4738 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CN1N=C(C)C=C1C(=O)NC2=CC(OC3=NN4C=C(NC(=O)C5CC5)N=C4C=C3)=CC=C2C
InChI
InChIKey=DZFZXPPHBWCXPQ-UHFFFAOYSA-N
InChI=1S/C23H23N7O3/c1-13-4-7-16(11-17(13)24-23(32)18-10-14(2)27-29(18)3)33-21-9-8-20-25-19(12-30(20)28-21)26-22(31)15-5-6-15/h4,7-12,15H,5-6H2,1-3H3,(H,24,32)(H,26,31)
| Molecular Formula | C23H23N7O3 |
| Molecular Weight | 445.4738 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
DescriptionCurator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/21182308
Curator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/21182308
TAK-593 is an oral formulation containing a small-molecule receptor tyrosine kinase inhibitor of both vascular endothelial growth factor receptor 2 (VEGFR2) and platelet-derived growth factor receptor (PDGFR) with potential antineoplastic activity. TAK-593 selectively binds to and inhibits VEGFR and PDGFR, which may result in the inhibition of angiogenesis and tumor cell proliferation. It was in the phase I of clinical trial in subjects with nonhematologic advanced cancer and it was discontinued.
Approval Year
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
0.056 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23498918 |
0.5 mg/kg single, oral dose: 0.5 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
TAK-593 plasma | Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: FED |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
0.226 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23498918 |
0.5 mg/kg single, oral dose: 0.5 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
TAK-593 plasma | Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: FED |
|
0.571 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23498918 |
0.25 mg/kg single, intravenous dose: 0.25 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
TAK-593 plasma | Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: FED |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Biochemical characterization of TAK-593, a novel VEGFR/PDGFR inhibitor with a two-step slow binding mechanism. | 2011 Feb 8 |
|
| Anti-angiogenic and anti-tumor effects of TAK-593, a potent and selective inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptor tyrosine kinase. | 2013 Apr |
|
| Discovery of N-[5-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)-2-methylphenyl]-1,3-dimethyl-1H-pyrazole-5-carboxamide (TAK-593), a highly potent VEGFR2 kinase inhibitor. | 2013 Apr 15 |
Sample Use Guides
Tablets of TAK-593 in 2 strengths: 1 mg and 4 mg tablets. Administration will initially be 4 mg, once a day and transition to 2 mg BID schedule dependant on safety.
Route of Administration:
Oral
In Vitro Use Guide
Curator's Comment: TAK-593 displayed competitive inhibition versus ATP. In addition, TAK-593 inhibited VEGFR2 and PDGFRβ in a time-dependent manner, classifying it as a type II kinase inhibitor. Analysis of enzyme-inhibitor preincubation experiments revealed that the binding of TAK-593 to VEGFR2 and PDGFRβ occurs via a two-step slow binding mechanism. Dissociation of TAK-593 from VEGFR2 was extremely slow (t(1/2) >17 h), and the affinity of TAK-593 at equilibrium (K(i)*) was less than 25 pM. Ligand displacement analysis with a fluorescent tracer confirmed the slow dissociation of TAK-593.
Unknown
| Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 09:12:54 GMT 2023
by
admin
on
Sat Dec 16 09:12:54 GMT 2023
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| Record UNII |
H3I42X8XX7
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| Record Status |
Validated (UNII)
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| Record Version |
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DB13093
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H3I42X8XX7
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24767976
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C79794
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CHEMBL2180604
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