| Identification | Back Directory | [Name]
TAS6417 | [CAS]
1661854-97-2 | [Synonyms]
TAS6417
CLN-081
TAS-6417;TAS 6417;TAS6417
(S)-N-(4-amino-6-methyl-5-(quinolin-3-yl)-8,9-dihydropyrimido[5,4-b]indolizin-8-yl)acrylamide
2-Propenamide, N-[(8S)-4-amino-8,9-dihydro-6-methyl-5-(3-quinolinyl)pyrimido[5,4-b]indolizin-8-yl]- | [Molecular Formula]
C23H20N6O | [MDL Number]
MFCD31715430 | [MOL File]
1661854-97-2.mol | [Molecular Weight]
396.44 |
| Chemical Properties | Back Directory | [Boiling point ]
756.6±60.0 °C(Predicted) | [density ]
1.40±0.1 g/cm3(Predicted) | [storage temp. ]
4°C, protect from light, stored under nitrogen | [solubility ]
DMSO:20.0(Max Conc. mg/mL);50.44(Max Conc. mM) | [form ]
Solid | [pka]
12.81±0.40(Predicted) | [color ]
White to yellow |
| Hazard Information | Back Directory | [Uses]
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 IC50 values ranging from 1.1-8.0 nM[1][2]. | [in vivo]
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[1].
?
Zipalertinib (TAS6417) had no effect on EGFR-independent proliferation in NCI-H23 or NCI-H460 cells[1].
?
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[1].
?
Zipalertinib (TAS6417) (100 and 200 mg/kg/day) prolongs survival of animals bearing lung cancer[1].
| Animal Model: | Mice implanted with NCI-H1975 EGFR D770_N771insSVD xenografts[1]. | | Dosage: | 50 and 100 mg/kg. | | Administration: | Orally once daily for 14 days. | | Result: | Showed marked tumor growth inhibition with treatment/control (T/C) ratios of 51% and 19%, respectively. |
| [IC 50]
EGFR: 1.1-8.0 nM (IC50) | [References]
[1] Hasako S, et al. TAS6417, A Novel EGFR Inhibitor Targeting Exon 20 Insertion Mutations. Mol Cancer Ther. 2018 Aug;17(8):1648-1658. DOI:10.1158/1535-7163.MCT-17-1206
[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. DOI:10.1158/1541-7786.MCR-19-0419 |
|
| Company Name: |
Twochem Co.Ltd Gold
|
| Tel: |
021-021-58111628 15800915896 |
| Website: |
www.twochem.com |
|