Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C20H15ClN4.2ClH |
| Molecular Weight | 419.735 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.Cl.ClC1=CC=C(NC2=C3C=CC=CC3=C(CC4=CC=NC=C4)N=N2)C=C1
InChI
InChIKey=AZUQEHCMDUSRLH-UHFFFAOYSA-N
InChI=1S/C20H15ClN4.2ClH/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);2*1H
DescriptionCurator's Comment: description was created based on several sources, including:
http://www.drugbank.ca/drugs/DB04879
https://en.wikipedia.org/wiki/Vatalanib
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
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
| 77.0 nM [IC50] | |||
| 37.0 nM [IC50] | |||
Target ID: CHEMBL1955 |
660.0 nM [IC50] | ||
Target ID: CHEMBL1936 |
730.0 nM [IC50] | ||
Target ID: CHEMBL1913 |
580.0 nM [IC50] | ||
Target ID: CHEMBL1844 |
1.4 µM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Unknown Approved UseUnknown |
|||
| Primary | Unknown Approved UseUnknown |
|||
| Primary | Unknown Approved UseUnknown |
Doses
| Dose | Population | Adverse 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%) Sources: 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%) |
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) Sources: hypertension (1 pt) |
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) Sources: emesis (2 patients) Anorexia (1 pt) |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| 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: |
PubMed
| Title | Date | PubMed |
|---|---|---|
| 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 |
|
| New anilinophthalazines as potent and orally well absorbed inhibitors of the VEGF receptor tyrosine kinases useful as antagonists of tumor-driven angiogenesis. | 2000 Jun 15 |
|
| Effect of VEGF receptor inhibitor PTK787/ZK222584 [correction of ZK222548] combined with ionizing radiation on endothelial cells and tumour growth. | 2001 Dec 14 |
|
| Inhibition of growth and metastasis of human pancreatic cancer growing in nude mice by PTK 787/ZK222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases. | 2001 Oct |
|
| Blockade of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling for therapy of metastatic human pancreatic cancer. | 2002 Apr 1 |
|
| 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 |
|
| PTK/ZK (Novartis). | 2003 Aug |
|
| The kinase inhibitor PKC412 suppresses epiretinal membrane formation and retinal detachment in mice with proliferative retinopathies. | 2003 Aug |
|
| 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 |
|
| Antiangiogenic therapy: more promise and, yet again, more questions. | 2003 Nov 1 |
|
| Identification of a new chemical class of potent angiogenesis inhibitors based on conformational considerations and database searching. | 2003 Sep 15 |
|
| A dual-color fluorescence imaging-based system for the dissection of antiangiogenic and chemotherapeutic activity of molecules. | 2004 Oct |
|
| Protein kinase inhibitors: novel tools in cancer therapy. | 2004 Sep |
|
| 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 |
|
| Intravitreal injection of specific receptor tyrosine kinase inhibitor PTK787/ZK222 584 improves ischemia-induced retinopathy in mice. | 2005 Jun |
|
| The assessment of antiangiogenic and antivascular therapies in early-stage clinical trials using magnetic resonance imaging: issues and recommendations. | 2005 May 9 |
|
| [Some new findings in the pathogenesis of myeloproliferative disorders and new insight into more effective treatment]. | 2006 |
|
| 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 |
|
| Growth inhibition of orthotopic anaplastic thyroid carcinoma xenografts in nude mice by PTK787/ZK222584 and CPT-11. | 2006 May |
|
| Role of platelet-derived growth factor and vascular endothelial growth factor in obliterative airway disease. | 2006 Nov 15 |
|
| 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 |
|
| 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 |
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
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212141-51-0
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DTXSID5049073
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SUBSTANCE RECORD
