The half-life of the main drugs used in clinical practice to treat advanced thyroid cancer and the half-maximal inhibitory concentration (IC50) of these drugs against the most common tyrosine kinase receptors
Drug
Half-life
RET
PDGFR
FGFR
EGFR
VEGFR
BRAFV600E
NTRK
Other molecular targets
Lenvatinib
28 h
35 nM
39 nM
46 nM
-
22; 4; 5.2 nM*
-
-
c-KIT, KIF5B-RET, CCDC6-RET, NcoA4-RET
Sorafenib
25–48 h
47 μM
57 μM
-
-
9; 28; 7 μM *
38 μM
-
c-KIT, FLT3
Cabozantinib
55 h
4 nM
234 nM
-
-
12; 0.035; 6 nM*
-
-
c-KIT, MET, KIF5B-RET
Selpercatinib
32 h
0.4 nM
-
-
-
0.92–67.8 nM**
-
-
-
Vandetanib
19 days
130 nM
-
-
500 nM
40; 110 nM#
-
-
RET-KIF5B
Pralsetinib
14.7 h
0.4 nM
-
-
-
35 nM°
-
-
KIF5B-RET, CCDC6-RET, FLT3
Entrectinib
20–40 h
-
-
-
-
-
-
0.002; 0.00057; 0.0011 nM^
ROS, ALK
Larotrectinib
3 h
-
-
-
-
-
-
6.5; 8.1; 10.6 nM^
-
Dabrafenib
8 h
-
-
-
-
-
0.5 nM
-
-
Trametinib
127 h
-
-
-
-
-
0.48 nM
-
MEK
RET: REarranged during Transfection receptor; PDGFR: platelet-derived growth factor receptor; FGFR: fibroblast growth factor receptor; EGFR: epidermal growth factor receptor; VEGFR: vascular endothelial growth factor receptor; BRAFV600E: valine to the glutamic acid substitution of BRAF gene; NTRK: neurotrophic tyrosine receptor kinase; KIT: v-kit Hardy Zuckerman 4 feline sarcoma viral oncogene; KIF5B-RET, CCDC6-RET and NcoA4-RET: RET gene fusions; FLT3: Fms-like tyrosine kinase 3; MET: hepatocyte growth factor (HGF) receptor; MEK: mitogen-activated protein kinase; ROS: reactive oxygen species; ALK: anaplastic lymphoma kinase; - : no pharmacological action against these tyrosine kinase receptors. * respectively for VEGFR1, VEGFR2 and VEGFR3; ** range of inhibition on VEGFR1 and VEGFR3; # respectively for VEGFR2 and VEGFR3; ° only for VEGFR2; ^ respectively for NTRK-1, NTRK-2 and NTRK-3
Declarations
Author contributions
LV and AM: Conceptualization, Data curation, Investigation, Methodology, Writing—original draft, Writing—review & editing. Both authors read and approved the submitted version.
Conflicts of interest
The authors declare that they have no conflicts of interest.
Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.
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