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Details

Stereochemistry ACHIRAL
Molecular Formula C20H15ClN4
Molecular Weight 346.8136
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VATALANIB

SMILES

c1ccc2c(c1)c(Cc3ccncc3)nnc2Nc4ccc(cc4)Cl

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 346.8136
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
PTK787/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration.
2000 Apr 15
Vascular endothelial growth factor (VEGF) receptor-2 antagonists inhibit VEGF- and basic fibroblast growth factor-induced angiogenesis in vivo and in vitro.
2001 Dec
Dissection of angiogenic signaling in zebrafish using a chemical genetic approach.
2002 Apr
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
New drugs in acute myeloid leukemia.
2002 Sep
PTK/ZK (Novartis).
2003 Aug
p190RhoGAP can act to inhibit PDGF-induced gliomas in mice: a putative tumor suppressor encoded on human chromosome 19q13.3.
2003 Feb 15
American Society of Clinical Oncology-39th Annual Meeting. Angiogenesis. 31 May-3 June 2003, Chicago, IL, USA.
2003 Jul
Vascular endothelial growth factor receptor tyrosine kinase inhibitors: PTK787/ZK 222584.
2003 Jun
MRI monitoring of tumor response following angiogenesis inhibition in an experimental human breast cancer model.
2003 Mar
Identification of a new chemical class of potent angiogenesis inhibitors based on conformational considerations and database searching.
2003 Sep 15
PTK787/ZK222584, an inhibitor of vascular endothelial growth factor receptor tyrosine kinases, decreases glioma growth and vascularization.
2004 Aug
Advances in the structural biology, design and clinical development of VEGF-R kinase inhibitors for the treatment of angiogenesis.
2004 Mar 11
Dissecting tumor maintenance requirements using bioluminescence imaging of cell proliferation in a mouse glioma model.
2004 Nov
A dual-color fluorescence imaging-based system for the dissection of antiangiogenic and chemotherapeutic activity of molecules.
2004 Oct
The histone deacetylase inhibitor NVP-LAQ824 inhibits angiogenesis and has a greater antitumor effect in combination with the vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK222584.
2004 Sep 15
[Problems in the current target therapy of malignancies].
2005
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
Antivascular therapy of oral tongue squamous cell carcinoma with PTK787.
2005 Dec
Phacilitate Cell and Gene Therapy Forum 2005. Cell and gene therapy: a corporate perspective. 24-26 January 2005, Washington, DC, USA.
2005 Mar
Update on angiogenesis inhibitors.
2005 Nov
Clinical implications of angiogenesis in cancers.
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
Lessons from phase III clinical trials on anti-VEGF therapy for cancer.
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
Growth inhibition of orthotopic anaplastic thyroid carcinoma xenografts in nude mice by PTK787/ZK222584 and CPT-11.
2006 May
1-(Azolyl)-4-(aryl)-phthalazines: novel potent inhibitors of VEGF receptors I and II.
2006 Nov
Correlation of relative permeability and relative cerebral blood volume in high-grade cerebral neoplasms.
2006 Oct
New molecular targeted therapies in thyroid cancer.
2006 Sep
Targeted therapy of breast cancer.
2007
Vatalanib: the clinical development of a tyrosine kinase inhibitor of angiogenesis in solid tumours.
2007 Mar
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 Jun 25 23:40:43 UTC 2021
Edited
by admin
on Fri Jun 25 23:40:43 UTC 2021
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
BAY-86-5127
Code English
NVP-PTK787
Code English
CGP-79787
Code English
VATALANIB [INN]
Common Name English
K-222584
Code English
VATALANIB [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C1967
Created by admin on Fri Jun 25 23:40:43 UTC 2021 , Edited by admin on Fri Jun 25 23:40:43 UTC 2021
NCI_THESAURUS C1742
Created by admin on Fri Jun 25 23:40:43 UTC 2021 , Edited by admin on Fri Jun 25 23:40:43 UTC 2021
Code System Code Type Description
PUBCHEM
151194
Created by admin on Fri Jun 25 23:40:43 UTC 2021 , Edited by admin on Fri Jun 25 23:40:43 UTC 2021
PRIMARY
FDA UNII
5DX9U76296
Created by admin on Fri Jun 25 23:40:43 UTC 2021 , Edited by admin on Fri Jun 25 23:40:43 UTC 2021
PRIMARY
DRUG BANK
DB04879
Created by admin on Fri Jun 25 23:40:43 UTC 2021 , Edited by admin on Fri Jun 25 23:40:43 UTC 2021
PRIMARY
CAS
212141-54-3
Created by admin on Fri Jun 25 23:40:43 UTC 2021 , Edited by admin on Fri Jun 25 23:40:43 UTC 2021
PRIMARY
EPA CompTox
212141-54-3
Created by admin on Fri Jun 25 23:40:43 UTC 2021 , Edited by admin on Fri Jun 25 23:40:43 UTC 2021
PRIMARY
MERCK INDEX
M11400
Created by admin on Fri Jun 25 23:40:43 UTC 2021 , Edited by admin on Fri Jun 25 23:40:43 UTC 2021
PRIMARY Merck Index
MESH
C404768
Created by admin on Fri Jun 25 23:40:43 UTC 2021 , Edited by admin on Fri Jun 25 23:40:43 UTC 2021
PRIMARY
NCI_THESAURUS
C1868
Created by admin on Fri Jun 25 23:40:43 UTC 2021 , Edited by admin on Fri Jun 25 23:40:43 UTC 2021
PRIMARY
ChEMBL
CHEMBL101253
Created by admin on Fri Jun 25 23:40:43 UTC 2021 , Edited by admin on Fri Jun 25 23:40:43 UTC 2021
PRIMARY
EVMPD
SUB26999
Created by admin on Fri Jun 25 23:40:43 UTC 2021 , Edited by admin on Fri Jun 25 23:40:43 UTC 2021
PRIMARY
INN
7994
Created by admin on Fri Jun 25 23:40:43 UTC 2021 , Edited by admin on Fri Jun 25 23:40:43 UTC 2021
PRIMARY
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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