| Stereochemistry | ACHIRAL |
| Molecular Formula | C22H24BrFN4O2 |
| Molecular Weight | 475.354 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=CC2=C(C=C1OCC3CCN(C)CC3)N=CN=C2NC4=CC=C(Br)C=C4F
InChI
InChIKey=UHTHHESEBZOYNR-UHFFFAOYSA-N
InChI=1S/C22H24BrFN4O2/c1-28-7-5-14(6-8-28)12-30-21-11-19-16(10-20(21)29-2)22(26-13-25-19)27-18-4-3-15(23)9-17(18)24/h3-4,9-11,13-14H,5-8,12H2,1-2H3,(H,25,26,27)
Vandetanib, 4-anilinoquinazoline, is an anti-cancer drug that with the potential for use in a broad range of tumour types. In 2011 vandetanib (trade name Caprelsa) was approved by the FDA to treat nonresectable, locally advanced, or metastatic medullary thyroid cancer in adult patients. In vitro studies have shown that vandetanib inhibits the tyrosine kinase activity of the EGFR and VEGFR families, RET, BRK, TIE2, and members of the EPH receptor and Src kinase families. These receptor tyrosine kinases are involved in both normal cellular function and pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, and maintenance of the tumor microenvironment. Vandetanib was shown to inhibit epidermal growth factor (EGF)-stimulated receptor tyrosine kinase phosphorylation in tumor cells and endothelial cells and VEGF-stimulated tyrosine kinase phosphorylation in endothelial cells. Vandetanib administration reduced tumor cell-induced angiogenesis, tumor vessel permeability, and inhibited tumor growth and metastasis in mouse models of cancer.
CNS Activity
Originator
Approval Year
Doses
AEs
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
Drug as perpetrator
Drug as victim
Tox targets
Sourcing
Sample Use Guides
300 mg once daily may be taken with or without food. Dosage reduction may be necessary in the event of severe toxicities or QTc interval prolongation. The starting dose is 200 mg in patients with moderate to severe renal impairment.
Route of Administration:
Oral
Used in in vitro co-culture tubule formation model consisting of HUVECs and human fibroblasts vandetanib potently inhibited each of the tubule growth parameters measured (number of branch points [IC50 = 33.23 nM], total vessel length [IC50 = 60.97 nM], tubule area [IC50 = 92.70 nM]), at potencies consistent with the potency of vandetanib for inhibition of VEGF-stimulated proliferation of HUVECs.
ACTIVE MOIETY
METABOLITE ACTIVE (PARENT)
METABOLITE INACTIVE (PARENT)
