zipalertinib (TAS6417)

Catalog No.S8814 Batch:S881401

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Technical Data

Formula

C23H20N6O
Molecular Weight 396.44 CAS No. 1661854-97-2
Solubility (25°C)* In vitro DMSO 79 mg/mL (199.27 mM)
Ethanol 79 mg/mL (199.27 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description zipalertinib (TAS6417) is a novel EGFR inhibitor that targets EGFR exon 20 insertion mutations while sparing wild-type (WT) EGFR. IC50 values ranges from 1.1 ± 0.1 to 8.0 ± 1.1 nmol/L.
Targets
EGFR(d746-750/T790M) [1]
(Cell-free assay)		 TXK [1]
(Cell-free assay)		 EGFR(d746-750) [1]
(Cell-free assay)		 EGFR L858R [1]
(Cell-free assay)		 EGFR T790M/L858R [1]
(Cell-free assay)		 View More
1.1 nM 1.1 nM 1.4 nM 1.9 nM 2 nM
In vitro

Of the 255 kinases tested, TAS6417 inhibits 25 kinases other than EGFR 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. TAS6417 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. TAS6417 has no effect on EGFR-independent proliferation in NCI-H23 or NCI-H460 cells[1].
In vivo

TAS6417 causes persistent tumor regression in vivo in EGFR exon 20 insertion-driven tumor models. The tumor regression occurrs quickly after TAS6417 treatment and persists during the treatment period. Pharmacokinetic analysis reveals that the plasma concentration of TAS6417, 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. TAS6417 inhibits mutant EGFR in tumors but not WT EGFR in skin tissues. It prolongs survival of animals bearing lung cancer[1].

Protocol (from reference)

Cell Assay:

[1]
  • Cell lines

    LXF 2478L cells and NCI-H1975 EGFR D770_N771insSVD cells

  • Concentrations

    0-1 μM

  • Incubation Time

    6 and 24 hours

  • Method

    The cells are cultured with TAS6417 or afatinib and harvested 6 and 24 hours after treatment. Phosphorylation of EGFR-Tyr1068, AKT-Ser473, and ERK1/2-Thr202/Tyr204 and expression of BIM and cleaved PARP are determined using immunoblotting analysis.
Animal Study:

[1]
  • Animal Models

    BALB/cAJcl-nu/nu nude mice with intrapulmonary NCI-H1975 EGFR D770_N771insSVD xenografts

  • Dosages

    100 mg/kg/day and 200 mg/kg/day

  • Administration

    oral

Selleck's zipalertinib (TAS6417) has been cited by 3 publications

Profiling of ERBB receptors and downstream pathways reveals selectivity and hidden properties of ERBB4 antagonists [ iScience, 2024, 27(2):108839] PubMed: 38303712
Protocol for identifying properties of ERBB receptor antagonists using the barcoded ERBBprofiler assay [ STAR Protoc, 2024, 5(2):102987] PubMed: 38635397
Secondary Mutations of the EGFR Gene That Confer Resistance to Mobocertinib in EGFR Exon 20 Insertion [ J Thorac Oncol, 2023, S1556-0864(23)00797-9] PubMed: 37666482

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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