Limertinib

SKU: orb1694220

Description

Limertinib (ASK120067) is an oral, potent, and selective EGFR tyrosine kinase inhibitor designed to target the T790M resistance mutation. It is a valuable research tool for investigating non-small cell lung cancer (NSCLC) in both in vitro cellular assays and in vivo animal models.

Research Area

Cardiovascular Research, Signal Transduction

Key Properties

• CAS Number: 1934259-00-3
• MW: 546.06
• Purity: 99.77% (May vary between batches)
• Formula: C₂₉H₃₂ClN₇O₂
• SMILES: O=C(C=C)NC1=CC(NC2=NC=C(Cl)C(=N2)NC=3C=CC=4C=CC=CC4C3)=C(OC)C=C1N(C)CCN(C)C
• Target: EGFR
• Solubility: 10% DMSO+40% PEG300+5% Tween-80+45% Saline:2 mg/mL (3.66 mM);DMSO:40 mg/mL (73.25 mM)

Bioactivity

• Target IC50:
  EGFR (T790M):0.5 nM (IC50)|EGFR (exon 19 deletion):0.5 nM (IC50)|PC9 cells:6 nM|EGFR (L858R/T790M):0.3 nM (IC50)|H1975 cells (EGFR T790M):12 nM|HCC827 cells (sensitive mutation):2 nM|EGFR (WT):6 nM
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• In Vivo:
  By oral administration (5-20 mg/kg once daily for 21 days), Limertinib significantly slowed down tumor growth with a tumor growth inhibition (TGI) of 85.7%. When administered at a dose of 10 mg/kg, Limertinib significantly reduced tumor growth with a TGI rate of 99.3%, showing similar efficacy to Osimertinib.
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• In Vitro:
  In an in vitro kinase assay, Limertinib exhibited potent inhibition of EGFR L858R/T790M and EGFR T790M resistance mutants with IC50 values of 0.3 nM and 0.5 nM, respectively, as well as a sensitive mutant with deletion of EGFR exon 19 (IC50 = 0.5 nM). In comparison, Limertinib has an IC50 of 6 nM against wild-type EGFR (EGFRWT). Limertinib selectively inhibited the proliferation of EGFR-mutant cell lines and exhibited significant antiproliferative activity in non-small cell lung cancer (NSCLC) cells harboring mutant EGFR, with IC50 values of 12 nM, 6 nM, and 2 nM for NCI-H1975 (T790M mutation), PC-9, and HCC827 cells (sensitive mutation), respectively. In the concentration range of 0.1-100 nM, Limertinib inhibits phosphorylation of EGFR at tyrosine residue 1068 and inhibits phosphorylation of its downstream signaling proteins, AKT and ERK, in NCI-H1975 cells (EGFR L858R/T790M), even at low concentrations of 0.1-1 nM. In addition, it reduced the expression levels of p-EGFR, p-Akt, and p-ERK in EGFR WT A431 cells when Limertinib concentration reached 10-100 nM.
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

ASK120067, ASK-120067, ASK 120067

Compound Identifiers

PubChem CID

121371196