Zipalertinib (TAS6417; CLN-081) 是高效的、具有口服活性的、广泛的 EGFR 突变型的抑制剂，可独特的结合到 EGFR 铰链区的 ATP 结合位点，其 IC₅₀ 值为 1.1-8.0 nM。

Zipalertinib (TAS6417; CLN-081) is a highly effective, orally active and pan-mutation-selective EGFR tyrosine kinase inhibitor with a unique scaffold fitting into the ATP-binding site of the EGFR hinge region, with IC 50 values ranging from 1.1-8.0 nM.

Solid

EGFR 1.1-8.0 nM (IC50)

Zipalertinib (TAS6417) inhibits EGFR phosphorylation and downstream molecules in NSCLC cell lines expressing EGFR exon 20 insertions, resulting in caspase activation.
Zipalertinib (TAS6417) is a robust inhibitor against the most common EGFR mutations (exon 19 deletions and L858R) and the most potent against cells harboring EGFR-T790M (1st/2nd generation TKI resistance mutation).
Zipalertinib (TAS6417) covalently modified the cysteine residue at position 797 of recombinant EGFR harboring an in-frame insertion mutation in the exon 20 region.
Zipalertinib (TAS6417) inhibits EGFR signal transduction, leading to cell growth inhibition and apoptosis induction in NSCLC cells driven by EGFR exon 20 insertion mutations.
Zipalertinib (TAS6417) (0-10 μM) inhibits cell proliferation and EGFR signaling in NSCLC cell lines harboring EGFR common mutations in the presence or a

Zipalertinib (TAS6417) (10-200 mg/kg) causes persistent tumor regression in vivo in EGFR exon 20 insertion-driven tumor models. TAS6417 inhibits mutant EGFR in tumors but not WT EGFR in skin tissues.
Zipalertinib (TAS6417) had no effect on EGFR-independent proliferation in NCI-H23 or NCI-H460 cells.
Zipalertinib (TAS6417) administered at 20 mg/kg, which achieves complete suppression of tumor growth, induces a significant decrease in pEGFR, leading to reduction of pAKT and pERK at 1 h. The inhibitory effect is still noted at 6 h, and phosphorylation of EGFR, ATK, and ERK recovered by 24 h.
Zipalertinib (TAS6417) (100 and 200 mg/kg/day) prolongs survival of animals bearing lung cancer.
has not independently confirmed the accuracy of these methods. They are for reference only.

Room temperature in continental US; may vary elsewhere.

4°C, protect from light, stored under nitrogen In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)

[1]. Hasako S, et al. TAS6417, A Novel EGFR Inhibitor Targeting Exon 20 Insertion Mutations. Mol Cancer Ther. 2018 Aug;17(8):1648-1658.
[2]. Hibiki Udagawa, et al. TAS6417/CLN-081 Is a Pan-Mutation-Selective EGFR Tyrosine Kinase Inhibitor with a Broad Spectrum of Preclinical Activity against Clinically Relevant EGFR Mutations. Mol Cancer Res. 2019 Nov;17(11):2233-2243.

In Vitro: DMSO : 22.73 mg/mL (57.34 mM; Need ultrasonic)配制储备液