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.

Product information

CAS Number: 1661854-97-2

Molecular Weight: 396.44

Formula: C23H20N6O

Chemical Name: N-[(8S)-4-amino-6-methyl-5-(quinolin-3-yl)-8H,9H-pyrimido[5,4-b]indolizin-8-yl]prop-2-enamide

Smiles: CC1=C[C@@H](CN2C3=NC=NC(N)=C3C(=C21)C1C=NC2=CC=CC=C2C=1)NC(=O)C=C

InChiKey: MKCYPWYURWOKST-INIZCTEOSA-N

InChi: InChI=1S/C23H20N6O/c1-3-18(30)28-16-8-13(2)21-19(15-9-14-6-4-5-7-17(14)25-10-15)20-22(24)26-12-27-23(20)29(21)11-16/h3-10,12,16H,1,11H2,2H3,(H,28,30)(H2,24,26,27)/t16-/m0/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 22.73 mg/mL (57.34 mM; Need ultrasonic).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

TAS6417 inhibits EGFR phosphorylation and downstream molecules in NSCLC cell lines expressing EGFR exon 20 insertions, resulting in caspase activation. 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). TAS6417 covalently modified the cysteine residue at position 797 of recombinant EGFR harboring an in-frame insertion mutation in the exon 20 region. TAS6417 inhibits EGFR signal transduction, leading to cell growth inhibition and apoptosis induction in NSCLC cells driven by EGFR exon 20 insertion mutations. TAS6417 (0-10 μM) inhibits cell proliferation and EGFR signaling in NSCLC cell lines harboring EGFR common mutations in the presence or absence of T790M.

In Vivo:

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. TAS6417 had no effect on EGFR-independent proliferation in NCI-H23 or NCI-H460 cells. 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. TAS6417 (100 and 200 mg/kg/day) prolongs survival of animals bearing lung cancer.

Products are for research use only. Not for human use.