Home Angiogenesis EGFR inhibitor zipalertinib (TAS6417)

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zipalertinib (TAS6417) EGFR inhibitor

Cat.No.S8814

zipalertinib (TAS6417) is a novel EGFR inhibitor that targets EGFR exon 20 insertion mutations while sparing wild-type (WT) EGFR, with IC50 values ranging from 1.1 ± 0.1 to 8.0 ± 1.1 nmol/L.
zipalertinib (TAS6417) EGFR inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 396.44

Jump to Mechanism of Action Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: S881401 DMSO]79 mg/mL]false]Ethanol]79 mg/mL]false]Water]Insoluble]false Purity: 99.86%
99.86

Chemical Information, Storage & Stability

Molecular Weight 396.44 Formula

C23H20N6O

 Storage (From the date of receipt) 3 years -20°C powder
CAS No. 1661854-97-2 -- Storage of Stock Solutions

Synonyms CLN-081, TPC-064 Smiles CC1=CC(CN2C1=C(C3=C(N=CN=C32)N)C4=CC5=CC=CC=C5N=C4)NC(=O)C=C

Solubility

In vitro
Batch:

DMSO : 79 mg/mL (199.27 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 79 mg/mL

Water : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
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In vivo Formulation Calculator (Clear solution)

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Mechanism of Action

Targets/IC50/Ki
EGFR(d746-750/T790M) [1]
(Cell-free assay)
1.1 nM
TXK [1]
(Cell-free assay)
1.1 nM
EGFR(d746-750) [1]
(Cell-free assay)
1.4 nM
EGFR L858R [1]
(Cell-free assay)
1.9 nM
EGFR T790M/L858R [1]
(Cell-free assay)
2 nM
BMX [1]
(Cell-free assay)
3.7 nM
HER4 [1]
(Cell-free assay)
4 nM
EGFR (T790M) [1]
(Cell-free assay)
4.1 nM
EGFR (L861Q) [1]
(Cell-free assay)
5.5 nM
EGFR WT [1]
(Cell-free assay)
8 nM
In vitro

Zipalertinib (TAS6417) inhibits 25 kinases other than EGFR among the 255 tested, with IC50 values less than 1,000 nmol/L, which was 100 times higher than its IC50 value against WT EGFR. It inhibits only six kinases containing TXK, BMX, HER4, TEC, BTK, and JAK3, with IC50 values less than 10 times that against WT EGFR. This compound inhibits proliferation of Ba/F3 cells driven by various EGFR exon 20 insertion mutations, with IC50 values ranging from 5.05 ± 1.33 nmol/L to 150 ± 53 nmol/L. It also suppresses the growth of cells expressing exon 20 insertion mutations of the EGFR gene, with a GI50 value of 86.5 ± 28.5 nmol/L for LXF 2478L cells and 45.4 ± 2.6 nmol/L for NCI-H1975 EGFR D770_N771insSVD cells. It has no effect on EGFR-independent proliferation in NCI-H23 or NCI-H460 cells[1].
In vivo

Zipalertinib (TAS6417) causes persistent tumor regression in vivo in EGFR exon 20 insertion-driven tumor models. The tumor regression occurrs quickly after treatment and persists during the treatment period. Pharmacokinetic analysis reveals that the plasma concentration of this compound, administered at 50 and 100 mg/kg to mice, decreases rapidly in the first 4 hours. In contrast, although the effective doses in the rat model exhibit lower maximum plasma concentration (Cmax) values than those in the mouse model, the plasma concentrations tend to be more persistent, lasting up to 8 hours. It inhibits mutant EGFR in tumors but not WT EGFR in skin tissues, and prolongs survival of animals bearing lung cancer[1].
References

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