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Details

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

SHOW SMILES / InChI
Structure of VATALANIB

SMILES

ClC1=CC=C(NC2=NN=C(CC3=CC=NC=C3)C4=C2C=CC=C4)C=C1

InChI

InChIKey=YCOYDOIWSSHVCK-UHFFFAOYSA-N
InChI=1S/C20H15ClN4/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/h1-12H,13H2,(H,23,25)

HIDE SMILES / InChI

Molecular Formula C20H15ClN4
Molecular Weight 346.813
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://www.drugbank.ca/drugs/DB04879 https://en.wikipedia.org/wiki/Vatalanib

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

Sources: DOI: 10.1007/s11224-011-9741-z

Approval Year

Doses

Doses

DosePopulationAdverse events​
750 mg 2 times / day multiple, oral (unknown)
MTD
Dose: 750 mg, 2 times / day
Route: oral
Route: multiple
Dose: 750 mg, 2 times / day
Sources:
unhealthy, ADULT
n = 31
Health Status: unhealthy
Condition: myeloid leukemia
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 31
Sources:
Other AEs: elevated transaminases, hypertension...
Other AEs:
elevated transaminases (3.2%)
hypertension (6.5%)
hyperbilirubinemia (3.2%)
Anorexia (3.2%)
eructation (3.2%)
Proteinuria (3.2%)
Asthenia (6.5%)
rash (3.2%)
thrombocytopenia (3.2%)
nausea (6.5%)
Fatigue (6.5%)
lethargy (3.2%)
dizziness (3.2%)
emesis (9.7%)
Sources:
1000 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 1000 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1000 mg, 2 times / day
Sources:
unhealthy, ADULT
n = 18
Health Status: unhealthy
Condition: myeloid leukemia
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 18
Sources:
DLT: Lethargy, hypertension...
Dose limiting toxicities:
Lethargy (1 pt)
hypertension (1 pt)
Sources:
1000 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 1000 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1000 mg, 2 times / day
Sources:
unhealthy
n = 35
Health Status: unhealthy
Condition: myelodysplastic syndrome
Sex: M+F
Food Status: UNKNOWN
Population Size: 35
Sources:
DLT: Nausea, emesis...
Dose limiting toxicities:
Nausea (3 patients)
emesis (2 patients)
Anorexia (1 pt)
Sources:
AEs

AEs

AESignificanceDosePopulation
Anorexia 3.2%
750 mg 2 times / day multiple, oral (unknown)
MTD
Dose: 750 mg, 2 times / day
Route: oral
Route: multiple
Dose: 750 mg, 2 times / day
Sources:
unhealthy, ADULT
n = 31
Health Status: unhealthy
Condition: myeloid leukemia
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 31
Sources:
Proteinuria 3.2%
750 mg 2 times / day multiple, oral (unknown)
MTD
Dose: 750 mg, 2 times / day
Route: oral
Route: multiple
Dose: 750 mg, 2 times / day
Sources:
unhealthy, ADULT
n = 31
Health Status: unhealthy
Condition: myeloid leukemia
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 31
Sources:
dizziness 3.2%
750 mg 2 times / day multiple, oral (unknown)
MTD
Dose: 750 mg, 2 times / day
Route: oral
Route: multiple
Dose: 750 mg, 2 times / day
Sources:
unhealthy, ADULT
n = 31
Health Status: unhealthy
Condition: myeloid leukemia
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 31
Sources:
elevated transaminases 3.2%
750 mg 2 times / day multiple, oral (unknown)
MTD
Dose: 750 mg, 2 times / day
Route: oral
Route: multiple
Dose: 750 mg, 2 times / day
Sources:
unhealthy, ADULT
n = 31
Health Status: unhealthy
Condition: myeloid leukemia
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 31
Sources:
eructation 3.2%
750 mg 2 times / day multiple, oral (unknown)
MTD
Dose: 750 mg, 2 times / day
Route: oral
Route: multiple
Dose: 750 mg, 2 times / day
Sources:
unhealthy, ADULT
n = 31
Health Status: unhealthy
Condition: myeloid leukemia
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 31
Sources:
hyperbilirubinemia 3.2%
750 mg 2 times / day multiple, oral (unknown)
MTD
Dose: 750 mg, 2 times / day
Route: oral
Route: multiple
Dose: 750 mg, 2 times / day
Sources:
unhealthy, ADULT
n = 31
Health Status: unhealthy
Condition: myeloid leukemia
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 31
Sources:
lethargy 3.2%
750 mg 2 times / day multiple, oral (unknown)
MTD
Dose: 750 mg, 2 times / day
Route: oral
Route: multiple
Dose: 750 mg, 2 times / day
Sources:
unhealthy, ADULT
n = 31
Health Status: unhealthy
Condition: myeloid leukemia
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 31
Sources:
rash 3.2%
750 mg 2 times / day multiple, oral (unknown)
MTD
Dose: 750 mg, 2 times / day
Route: oral
Route: multiple
Dose: 750 mg, 2 times / day
Sources:
unhealthy, ADULT
n = 31
Health Status: unhealthy
Condition: myeloid leukemia
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 31
Sources:
thrombocytopenia 3.2%
750 mg 2 times / day multiple, oral (unknown)
MTD
Dose: 750 mg, 2 times / day
Route: oral
Route: multiple
Dose: 750 mg, 2 times / day
Sources:
unhealthy, ADULT
n = 31
Health Status: unhealthy
Condition: myeloid leukemia
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 31
Sources:
Asthenia 6.5%
750 mg 2 times / day multiple, oral (unknown)
MTD
Dose: 750 mg, 2 times / day
Route: oral
Route: multiple
Dose: 750 mg, 2 times / day
Sources:
unhealthy, ADULT
n = 31
Health Status: unhealthy
Condition: myeloid leukemia
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 31
Sources:
Fatigue 6.5%
750 mg 2 times / day multiple, oral (unknown)
MTD
Dose: 750 mg, 2 times / day
Route: oral
Route: multiple
Dose: 750 mg, 2 times / day
Sources:
unhealthy, ADULT
n = 31
Health Status: unhealthy
Condition: myeloid leukemia
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 31
Sources:
hypertension 6.5%
750 mg 2 times / day multiple, oral (unknown)
MTD
Dose: 750 mg, 2 times / day
Route: oral
Route: multiple
Dose: 750 mg, 2 times / day
Sources:
unhealthy, ADULT
n = 31
Health Status: unhealthy
Condition: myeloid leukemia
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 31
Sources:
nausea 6.5%
750 mg 2 times / day multiple, oral (unknown)
MTD
Dose: 750 mg, 2 times / day
Route: oral
Route: multiple
Dose: 750 mg, 2 times / day
Sources:
unhealthy, ADULT
n = 31
Health Status: unhealthy
Condition: myeloid leukemia
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 31
Sources:
emesis 9.7%
750 mg 2 times / day multiple, oral (unknown)
MTD
Dose: 750 mg, 2 times / day
Route: oral
Route: multiple
Dose: 750 mg, 2 times / day
Sources:
unhealthy, ADULT
n = 31
Health Status: unhealthy
Condition: myeloid leukemia
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 31
Sources:
Lethargy 1 pt
DLT
1000 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 1000 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1000 mg, 2 times / day
Sources:
unhealthy, ADULT
n = 18
Health Status: unhealthy
Condition: myeloid leukemia
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 18
Sources:
hypertension 1 pt
DLT
1000 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 1000 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1000 mg, 2 times / day
Sources:
unhealthy, ADULT
n = 18
Health Status: unhealthy
Condition: myeloid leukemia
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 18
Sources:
Anorexia 1 pt
DLT
1000 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 1000 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1000 mg, 2 times / day
Sources:
unhealthy
n = 35
Health Status: unhealthy
Condition: myelodysplastic syndrome
Sex: M+F
Food Status: UNKNOWN
Population Size: 35
Sources:
emesis 2 patients
DLT
1000 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 1000 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1000 mg, 2 times / day
Sources:
unhealthy
n = 35
Health Status: unhealthy
Condition: myelodysplastic syndrome
Sex: M+F
Food Status: UNKNOWN
Population Size: 35
Sources:
Nausea 3 patients
DLT
1000 mg 2 times / day multiple, oral (unknown)
Studied dose
Dose: 1000 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1000 mg, 2 times / day
Sources:
unhealthy
n = 35
Health Status: unhealthy
Condition: myelodysplastic syndrome
Sex: M+F
Food Status: UNKNOWN
Population Size: 35
Sources:
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Blockade of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling for therapy of metastatic human pancreatic cancer.
2002 Apr 1
Quantitative and qualitative in vivo angiogenesis assay.
2002 Jul
PTK787/ZK 222584, a specific vascular endothelial growth factor-receptor tyrosine kinase inhibitor, affects the anatomy of the tumor vascular bed and the functional vascular properties as detected by dynamic enhanced magnetic resonance imaging.
2002 Jul 15
Vascular endothelial growth factor enhances cardiac allograft arteriosclerosis.
2002 May 28
New drugs in acute myeloid leukemia.
2002 Sep
The vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK222584 inhibits growth and migration of multiple myeloma cells in the bone marrow microenvironment.
2002 Sep 1
PTK/ZK (Novartis).
2003 Aug
Antiangiogenic therapy: more promise and, yet again, more questions.
2003 Nov 1
PTK787/ZK222584, an inhibitor of vascular endothelial growth factor receptor tyrosine kinases, decreases glioma growth and vascularization.
2004 Aug
An image worth a thousand lives?
2004 Jun
Effects of PTK787/ZK222584, a tyrosine kinase inhibitor, on the growth of a poorly differentiated thyroid carcinoma: an animal study.
2004 Mar
Soluble markers for the assessment of biological activity with PTK787/ZK 222584 (PTK/ZK), a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor in patients with advanced colorectal cancer from two phase I trials.
2005 Apr
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
Combined vascular endothelial growth factor and platelet-derived growth factor inhibition in rat cardiac allografts: beneficial effects on inflammation and smooth muscle cell proliferation.
2005 Jan 27
Phase I clinical and pharmacokinetic study of PTK/ZK, a multiple VEGF receptor inhibitor, in patients with liver metastases from solid tumours.
2005 Jun
Intravitreal injection of specific receptor tyrosine kinase inhibitor PTK787/ZK222 584 improves ischemia-induced retinopathy in mice.
2005 Jun
Enhanced susceptibility of irradiated tumor vessels to vascular endothelial growth factor receptor tyrosine kinase inhibition.
2005 Jun 15
Phacilitate Cell and Gene Therapy Forum 2005. Cell and gene therapy: a corporate perspective. 24-26 January 2005, Washington, DC, USA.
2005 Mar
PTK 787/ZK 222584, a tyrosine kinase inhibitor of all known VEGF receptors, represses tumor growth with high efficacy.
2005 Mar
Impact of adjuvant inhibition of vascular endothelial growth factor receptor tyrosine kinases on tumor growth delay and local tumor control after fractionated irradiation in human squamous cell carcinomas in nude mice.
2005 Mar 1
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
Targeting angiogenesis with vascular endothelial growth factor receptor small-molecule inhibitors: novel agents with potential in lung cancer.
2005 Sep
[Molecular targets in colon cancer].
2006 Apr
4-(Azolylphenyl)-phthalazin-1-amines: Novel inhibitors of VEGF receptors I and II.
2006 Dec
Biological agents versus chemotherapy in the treatment of colorectal cancer.
2006 Jul
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
Hetaryl imidazoles: a novel dual inhibitors of VEGF receptors I and II.
2006 Mar 1
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
Targeted therapy of breast cancer.
2007
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
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment: Vatalanib 1,250 mg orally daily in combination with FOLFOX-4. https://www.ncbi.nlm.nih.gov/pubmed/21464406
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
PTK787 (1 micro M) also blocks VEGF-induced migration of MM cells across an extracellular matrix.
Substance Class Chemical
Created
by admin
on Fri Dec 15 16:10:10 GMT 2023
Edited
by admin
on Fri Dec 15 16:10:10 GMT 2023
Record UNII
5DX9U76296
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
VATALANIB
INN   MI   USAN   WHO-DD  
USAN   INN  
Official Name English
VATALANIB [USAN]
Common Name English
VATALANIB [MI]
Common Name English
Vatalanib [WHO-DD]
Common Name English
BAY-86-5127
Code English
NVP-PTK787
Code English
CGP-79787
Code English
vatalanib [INN]
Common Name English
K-222584
Code English
Classification Tree Code System Code
NCI_THESAURUS C1967
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
NCI_THESAURUS C1742
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
Code System Code Type Description
PUBCHEM
151194
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
PRIMARY
FDA UNII
5DX9U76296
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
PRIMARY
DRUG BANK
DB04879
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
PRIMARY
CAS
212141-54-3
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
PRIMARY
EPA CompTox
DTXSID2046919
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
PRIMARY
MERCK INDEX
m11400
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
PRIMARY Merck Index
MESH
C404768
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
PRIMARY
SMS_ID
100000091584
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
PRIMARY
NCI_THESAURUS
C1868
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
PRIMARY
ChEMBL
CHEMBL101253
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
PRIMARY
EVMPD
SUB26999
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
PRIMARY
INN
7994
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
PRIMARY
WIKIPEDIA
Vatalanib
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
PRIMARY
CHEBI
90620
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
PRIMARY
USAN
QQ-50
Created by admin on Fri Dec 15 16:10:10 GMT 2023 , Edited by admin on Fri Dec 15 16:10:10 GMT 2023
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
EXCRETED UNCHANGED
FECAL
EXCRETED UNCHANGED
URINE
TARGET -> INHIBITOR
Related Record Type Details
METABOLITE -> PARENT
MINOR
FECAL
METABOLITE -> PARENT
TRACE AMOUNT
FECAL; PLASMA
METABOLITE -> PARENT
FECAL
METABOLITE -> PARENT
FECAL
METABOLITE -> PARENT
PLASMA
METABOLITE -> PARENT
URINE
METABOLITE -> PARENT
TRACE AMOUNT
FECAL
METABOLITE -> PARENT
URINE
METABOLITE -> PARENT
TRACE AMOUNT
FECAL; PLASMA
METABOLITE -> PARENT
MINOR
URINE
METABOLITE -> PARENT
MINOR
URINE
METABOLITE -> PARENT
TRACE AMOUNT
FECAL
METABOLITE -> PARENT
FECAL
METABOLITE -> PARENT
MINOR
URINE
METABOLITE -> PARENT
TRACE AMOUNT
PLASMA
METABOLITE -> PARENT
MINOR
URINE
METABOLITE -> PARENT
PLASMA
METABOLITE -> PARENT
TRACE AMOUNT
FECAL
METABOLITE -> PARENT
FECAL
METABOLITE -> PARENT
URINE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC SINGLE ORAL DOSE ADMINISTRATION

AT STEADY-STATE

Biological Half-life PHARMACOKINETIC SINGLE ORAL DOSE ADMINISTRATION

AT STEADY-STATE