U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C20H15ClN4.C4H6O4
Molecular Weight 464.901
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VATALANIB SUCCINATE

SMILES

OC(=O)CCC(O)=O.ClC1=CC=C(NC2=C3C=CC=CC3=C(CC4=CC=NC=C4)N=N2)C=C1

InChI

InChIKey=LLDWLPRYLVPDTG-UHFFFAOYSA-N
InChI=1S/C20H15ClN4.C4H6O4/c21-15-5-7-16(8-6-15)23-20-18-4-2-1-3-17(18)19(24-25-20)13-14-9-11-22-12-10-14;5-3(6)1-2-4(7)8/h1-12H,13H2,(H,23,25);1-2H2,(H,5,6)(H,7,8)

HIDE SMILES / InChI

Molecular Formula C20H15ClN4
Molecular Weight 346.813
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C4H6O4
Molecular Weight 118.088
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Vatalanib a potent oral tyrosine kinase inhibitor with a selective range of molecular targets, has been extensively investigated and has shown promising results in patients with solid tumors in early trials. Vatalanib selectively inhibits the tyrosine kinase domains of vascular endothelial growth factor (VEGF) receptor tyrosine kinases (important enzymes in the formation of new blood vessels that contribute to tumor growth and metastasis), platelet-derived growth factor (PDGF) receptor, and c-KIT. The adverse effects of vatalanib appear similar to those of other VEGF inhibitors. In the CONFIRM trials, the most common side effects were high blood pressure, gastrointestinal upset (diarrhea, nausea, and vomiting), fatigue, and dizziness.

CNS Activity

Originator

Approval Year

PubMed

PubMed

TitleDatePubMed
[Problems in the current target therapy of malignancies].
2005
PTK787/ZK222584, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor, reduces uptake of the contrast agent GdDOTA by murine orthotopic B16/BL6 melanoma tumours and inhibits their growth in vivo.
2005 Aug
Antivascular therapy of oral tongue squamous cell carcinoma with PTK787.
2005 Dec
Targeted Therapies in Cancer - Fourth International Congress. Angiogenesis inhibition.
2005 Dec
Perspectives in colorectal cancer - Sixth Annual Conference. Metastatic colorectal cancer.
2005 Dec
Vascular endothelial growth factor contributes to prostate cancer-mediated osteoblastic activity.
2005 Dec 1
Targeting vascular endothelial growth factor and angiogenesis for the treatment of colorectal cancer.
2005 Feb
Phase I clinical and pharmacokinetic study of PTK/ZK, a multiple VEGF receptor inhibitor, in patients with liver metastases from solid tumours.
2005 Jun
The realisation of targeted antitumour therapy.
2005 Jun
The antitumor and antiangiogenic activity of vascular endothelial growth factor receptor inhibition is potentiated by ErbB1 blockade.
2005 Jun 15
Enhanced susceptibility of irradiated tumor vessels to vascular endothelial growth factor receptor tyrosine kinase inhibition.
2005 Jun 15
Phase I study of the safety, tolerability, pharmacokinetics, and pharmacodynamics of PTK787/ZK 222584 administered twice daily in patients with advanced cancer.
2005 Jun 20
Phacilitate Cell and Gene Therapy Forum 2005. Cell and gene therapy: a corporate perspective. 24-26 January 2005, Washington, DC, USA.
2005 Mar
Arterial spin labeling blood flow magnetic resonance imaging for the characterization of metastatic renal cell carcinoma(1).
2005 Mar
PTK 787/ZK 222584, a tyrosine kinase inhibitor of all known VEGF receptors, represses tumor growth with high efficacy.
2005 Mar
Vatalanib (PTK787/ZK 222584) in combination with FOLFOX4 versus FOLFOX4 alone as first-line treatment for colorectal cancer: preliminary results from the CONFIRM-1 trial.
2005 May
Angiogenesis and lung cancer: prognostic and therapeutic implications.
2005 May 10
The assessment of antiangiogenic and antivascular therapies in early-stage clinical trials using magnetic resonance imaging: issues and recommendations.
2005 May 9
Update on angiogenesis inhibitors.
2005 Nov
Targeting multiple signal transduction pathways in lung cancer.
2005 Sep
Targeting angiogenesis with vascular endothelial growth factor receptor small-molecule inhibitors: novel agents with potential in lung cancer.
2005 Sep
Clinical implications of angiogenesis in cancers.
2006
[Some new findings in the pathogenesis of myeloproliferative disorders and new insight into more effective treatment].
2006
[Molecular targets in colon cancer].
2006 Apr
Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma.
2006 Aug
Treatment of metastatic colorectal cancer: from cytotoxic agents to molecular agents and multitargeted strategies.
2006 Dec
4-(Azolylphenyl)-phthalazin-1-amines: Novel inhibitors of VEGF receptors I and II.
2006 Dec
Lessons from phase III clinical trials on anti-VEGF therapy for cancer.
2006 Jan
Vascular endothelial growth factor receptor signaling is required for cardiac valve formation in zebrafish.
2006 Jan
Antagonism of sphingosine-1-phosphate receptors by FTY720 inhibits angiogenesis and tumor vascularization.
2006 Jan 1
Biological agents versus chemotherapy in the treatment of colorectal cancer.
2006 Jul
Tyrosine kinase inhibitors of vascular endothelial growth factor receptors in clinical trials: current status and future directions.
2006 Jul-Aug
Phase 1 study of PTK787/ZK 222584, a small molecule tyrosine kinase receptor inhibitor, for the treatment of acute myeloid leukemia and myelodysplastic syndrome.
2006 Jun
Biomarkers for assessment of pharmacologic activity for a vascular endothelial growth factor (VEGF) receptor inhibitor, PTK787/ZK 222584 (PTK/ZK): translation of biological activity in a mouse melanoma metastasis model to phase I studies in patients with advanced colorectal cancer with liver metastases.
2006 Jun
Ionizing radiation antagonizes tumor hypoxia induced by antiangiogenic treatment.
2006 Jun 1
Hetaryl imidazoles: a novel dual inhibitors of VEGF receptors I and II.
2006 Mar 1
Growth inhibition of orthotopic anaplastic thyroid carcinoma xenografts in nude mice by PTK787/ZK222584 and CPT-11.
2006 May
A simple, reproducible method for monitoring the treatment of tumours using dynamic contrast-enhanced MR imaging.
2006 May 22
1-(Azolyl)-4-(aryl)-phthalazines: novel potent inhibitors of VEGF receptors I and II.
2006 Nov
Rational design of RGD-albumin conjugates for targeted delivery of the VEGF-R kinase inhibitor PTK787 to angiogenic endothelium.
2006 Nov
Metabolism and disposition of vatalanib (PTK787/ZK-222584) in cancer patients.
2006 Nov
Role of platelet-derived growth factor and vascular endothelial growth factor in obliterative airway disease.
2006 Nov 15
Correlation of relative permeability and relative cerebral blood volume in high-grade cerebral neoplasms.
2006 Oct
High doses of tyrosine kinase inhibitor PTK787 enhance the efficacy of ischemic hypoxia for the treatment of hepatocellular carcinoma: dual effects on cancer cell and angiogenesis.
2006 Sep
New molecular targeted therapies in thyroid cancer.
2006 Sep
Targeted therapy of breast cancer.
2007
Biological therapy update in colorectal cancer.
2007 Apr
A phase IB, open-label dose-escalating study of the oral angiogenesis inhibitor PTK787/ZK 222584 (PTK/ZK), in combination with FOLFOX4 chemotherapy in patients with advanced colorectal cancer.
2007 Apr
Small molecule tyrosine kinase inhibitors in the treatment of solid tumors: an update of recent developments.
2007 Feb
Vatalanib: the clinical development of a tyrosine kinase inhibitor of angiogenesis in solid tumours.
2007 Mar
Patents

Sample Use Guides

In Vivo Use Guide
Vatalanib 1250 mg orally was given once daily (cohort 1) or 750-1250 mg once daily in an intra-patient dose escalating schedule (cohort 2) in 28-day cycles.
Route of Administration: Oral
In Vitro Use Guide
PTK787 (1 micro M) also blocks VEGF-induced migration of MM cells across an extracellular matrix.
Substance Class Chemical
Created
by admin
on Tue Oct 22 00:02:37 UTC 2019
Edited
by admin
on Tue Oct 22 00:02:37 UTC 2019
Record UNII
V5FUB77031
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
VATALANIB SUCCINATE
MI   WHO-DD  
Common Name English
ZK-222584
Code English
VATALANIB SUCCINATE [MI]
Common Name English
PTK-787/ZK-222584
Code English
1-PHTHALAZINAMINE, N-(4-CHLOROPHENYL)-4-(4-PYRIDINYLMETHYL)-, BUTANEDIOATE (1:1)
Systematic Name English
PTK787/ZK222584
Code English
PTK-787
Code English
ZK222584
Code English
PTK787
Code English
VATALANIB SUCCINATE [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C1742
Created by admin on Tue Oct 22 00:02:37 UTC 2019 , Edited by admin on Tue Oct 22 00:02:37 UTC 2019
NCI_THESAURUS C1967
Created by admin on Tue Oct 22 00:02:37 UTC 2019 , Edited by admin on Tue Oct 22 00:02:37 UTC 2019
Code System Code Type Description
CAS
212142-18-2
Created by admin on Tue Oct 22 00:02:37 UTC 2019 , Edited by admin on Tue Oct 22 00:02:37 UTC 2019
PRIMARY
NCI_THESAURUS
C74945
Created by admin on Tue Oct 22 00:02:37 UTC 2019 , Edited by admin on Tue Oct 22 00:02:37 UTC 2019
PRIMARY
PUBCHEM
151193
Created by admin on Tue Oct 22 00:02:37 UTC 2019 , Edited by admin on Tue Oct 22 00:02:37 UTC 2019
PRIMARY
EVMPD
SUB32570
Created by admin on Tue Oct 22 00:02:37 UTC 2019 , Edited by admin on Tue Oct 22 00:02:37 UTC 2019
PRIMARY
EPA CompTox
212142-18-2
Created by admin on Tue Oct 22 00:02:37 UTC 2019 , Edited by admin on Tue Oct 22 00:02:37 UTC 2019
PRIMARY
MERCK INDEX
M11400
Created by admin on Tue Oct 22 00:02:37 UTC 2019 , Edited by admin on Tue Oct 22 00:02:37 UTC 2019
PRIMARY Merck Index
Related Record Type Details
PARENT -> SALT/SOLVATE
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY