Chemical Property of Vandetanib
Chemical Property:
- Appearance/Colour:Yellow solid
- Vapor Pressure:0mmHg at 25°C
- Melting Point:240-243 °C
- Refractive Index:1.629
- Boiling Point:538.22 °C at 760 mmHg
- PKA:8.92±0.10(Predicted)
- Flash Point:279.306 °C
- PSA：59.51000
- Density:1.406 g/cm3
- LogP:5.01510
- Storage Temp.:-20?C Freezer
- Solubility.:Soluble in DMSO (30 mg/ml); Ethanol (10 mg/ml with warming)
- XLogP3:4.9
- Hydrogen Bond Donor Count:1
- Hydrogen Bond Acceptor Count:7
- Rotatable Bond Count:6
- Exact Mass:474.10667
- Heavy Atom Count:30
- Complexity:539
- Purity/Quality:
-
99% *data from raw suppliers
Vandetanib *data from reagent suppliers
Safty Information:
- Pictogram(s):
- Hazard Codes:
- Safety Statements:
24/25
- MSDS Files:
-
Useful:
- Drug Classes:Antineoplastic Agents
- Canonical SMILES:CN1CCC(CC1)COC2=C(C=C3C(=C2)N=CN=C3NC4=C(C=C(C=C4)Br)F)OC
- Recent ClinicalTrials:A Study of Pralsetinib Versus Standard of Care (SOC) for Treatment of RET-Mutated Medullary Thyroid Cancer (MTC).
- Recent EU Clinical Trials:A PHASE III, RANDOMIZED, OPEN-LABEL STUDY OF PRALSETINIB VERSUS STANDARD OF CARE FOR TREATMENT OF RET-MUTATED MEDULLARY THYROID CANCER
- Recent NIPH Clinical Trials:VERIFY
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Description
In April 2011, the U.S. FDA approved vandetanib (ZD6474) for the treatment of symptomatic or progressive medullary thyroid cancer (MTC) in adult patients with inoperable advanced ormetastatic disease. Vandetanib inhibits KDR/VEGFR2, VEGFR3, EGFR, and RET kinases with IC50's of 40, 110, 500, and <100 nM, respectively. In athymic mice bearing MTC tumors, a 14.5-fold reduction of tumor volume was observed after 45 days of treatment with vandetanib at 50 mg/kg/day. The decrease in tumor volume was accompanied by decreases in mitotic index (Ki67) and tumor angiogenesis in treated xenografts. Key steps in the synthesis of vandetanib include the displacement of the chlorine atom from 7-benzyloxy-4-chloro-6-methoxyquinazoline with 4-bromo-2- fluoroaniline under acidic conditions in a protic solvent and a Mitsunobu reaction of a N-protected piperidine alcohol with a phenol.
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Uses
Vandetanib (Zactima, ZD6474) is a potent inhibitor of VEGFR2 with IC50 of 40 nM. Vandetanib (ZD6474) is a potent inhibitor of VEGFR2 with IC50 of 40 nM Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor-2 and epidermal growth factor receptor kinase activity. The activity of Vandetanib plus Docetaxel was assessed
in patients with previously treated non-small-cell lung cancer (NSCLC). Vandetanib is a broad spectrum, orally available kinase inhibitor that targets primarily tyrosine kinases, including vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR), with IC50 values in the nanomolar range. It also potently blocks non-receptor tyrosine kinases, including ABL, RET, and SRC, as well as several serine/threonine kinases. Primarily because of its effects on receptor tyrosine kinases like VEGFR and EGFR, vandetanib inhibits angiogenesis, cell growth, and metastasis and is effective against certain forms of cancer.[Cayman Chemical]
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Clinical Use
Vandetanib, an oral VEGF, EGF, and RET receptor tyrosine kinase
inhibitor, was developed by AstraZeneca for the treatment of
symptomatic or aggressive medullary thyroid cancer (MTC) in patients
with advanced or metastatic disease. This is the first drug
approved for the treatment of MTC. Trials for other cancer indications
such as small-cell lung cancer (SCLC), breast cancer, head and
neck cancer, colorectal cancer, hormone-resistant prostate cancer,
and papillary thyroid cancer are currently being explored. While
AstraZeneca had previously developed ZD-4190 which displays
similar efficacy and pharmacokinetic profile to vandetanib, vandetanib
exhibited significantly improved solubility.
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Drug interactions
Potentially hazardous interactions with other drugs
Analgesics: possibly increased risk of ventricular
arrhythmias with methadone - avoid.
Anti-arrhythmics: possibly increased risk of
ventricular arrhythmias with amiodarone or
disopyramide - avoid.
Antibacterials: possibly increased risk of ventricular
arrhythmias with parenteral erythromycin and
moxifloxacin - avoid; concentration reduced by
rifampicin - avoid.
Antihistamines: possibly increased risk of ventricular
arrhythmias with mizolastine - avoid.
Antimalarials: possibly increased risk of ventricular
arrhythmias with artemether with lumefantrine -
avoid.
Antipsychotics: possibly increased risk of ventricular
arrhythmias with amisulpiride, chlorpromazine,
haloperidol, pimozide, sulpiride and zuclopenthixol
- avoid; avoid concomitant use with clozapine, risk
of agranulocytosis.
Beta-blockers: possibly increased risk of ventricular
arrhythmias with sotalol - avoid.
Cytotoxics: possibly increased risk of ventricular
arrhythmias with arsenic trioxide - avoid.
Hormone antagonist: possibly increased risk of
ventricular arrhythmias with toremifene - avoid.
5HT3
-receptor antagonists: possibly increased risk of
ventricular arrhythmias with ondansetron - avoid.
Pentamidine: possibly increased risk of ventricular
arrhythmias - avoid.
