Lazertinib

Catalog No.S8724 Batch:S872402

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Technical Data

Formula

C30H34N8O3
Molecular Weight 554.64 CAS No. 1903008-80-9
Solubility (25°C)* In vitro DMSO 5 mg/mL (9.01 mM)
Water Insoluble
Ethanol 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.)

Preparing Stock Solutions

Biological Activity

Description Lazertinib (YH25448,GNS-1480) is a potent, highly mutant-selective and irreversible EGFR-TKI with IC50 values of 1.7 nM, 2 nM, 5 nM, 20.6 nM and 76 nM for Del19/T790M, L858R/T790M, Del19, L85R and Wild type EGFR respectively, showing much higher IC50 values aganist ErbB2 and ErbB4.
Targets
Del19/T790M [1]
(Cell-free assay)		 L858R/T790M EGFR [1]
(Cell-free assay)		 Del19 [1]
(Cell-free assay)		 L85R [1]
(Cell-free assay)		 WT EGFR [1]
(Cell-free assay)
1.7 nM 2 nM 5 nM 20.6 nM 76 nM
In vitro

Lazertinib targets the activating EGFR mutations Del19 and L858R, as well as the T790M mutation, while sparing wild type. In NSCLC cell lines and primary cancer cells from patients harboring EGFR mutations, YH25448 more potently inhibits cancer cell growth and significantly increases tumor cell apoptosis compared to osimertinib[1]. In the cell proliferation assays, GI50 values of lazertinib are 6 nM, 5 nM, and 711 nM for H1975 cells (L858R/T790M), PC9 cells (del19) and H2073 cells (wt), respectively[2].
In vivo

In an in vivo mouse model implanted with H1975 cells, once-daily YH25448 treatment results in indramatic dose-dependent tumor regression in both subcutaneous and intracranial lesions with no abnormal signs such as skin keratosis. The plasma half-life of YH25448 is 5.9-6.8 hr, while the tumor to plasma AUC0-last ratio is 3.0-5.1 in tumor-bearing mice. YH25448 shows excellent penetration of the blood-brain bartier, achieving CSF concentrations exceeding the IC50 value for pEGFR inhibition. YH25448 shows superior efficacy for tumor regression in an EGFR mutant brain metastasis model[1].

Protocol (from reference)

Cell Assay:

[1]
  • Cell lines

    Ba/F3 cells

  • Concentrations

    5, 10, 100 nM

  • Incubation Time

    6 h

  • Method

    Ba/F3 cells overexpressing the indicated EGFR mutant are treated with YH25448 or osimertinib for 6 hours at the indicated concentrations. pEGFR levels are detected by Western blot analysis.
Animal Study:

[1]
  • Animal Models

    An intracranial tumor growth model (BALB/c nude mice inoculate with H1975-luc cells)

  • Dosages

    10 and 25 mg/kg

  • Administration

    --

Selleck's Lazertinib has been cited by 4 publications

Suppression of TNBC metastasis by doxazosin, a novel dual inhibitor of c-MET/EGFR [ J Exp Clin Cancer Res, 2023, 10.1186/s13046-023-02866-z] PubMed: 37924112
Acquired Resistance Mechanism of EGFR Kinase Domain Duplication to EGFR TKIs in Non-Small Cell Lung Cancer [ Cancer Res Treat, 2021, 10.4143/crt.2021.385] PubMed: 33940786
Preclinical Modeling of Osimertinib for NSCLC With EGFR Exon 20 Insertion Mutations [ J Thorac Oncol, 2019, 14(9):1556-1566] PubMed: 31108249
CD44 Facilitates Epithelial-to-Mesenchymal Transition Phenotypic Change at Acquisition of Resistance to EGFR Kinase Inhibitors in Lung Cancer. [ Mol Cancer Ther, 2018, 17(10):2257-2265] PubMed: 30049789

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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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