GNS-1480

GNS-1480 - Names and Identifiers

Name	N-{5-[(4-{4-[(dimethylamino)methyl]-3-phenyl-1H-pyrazol-1-yl}pyrimidin-2-yl)amino]-4-methoxy-2-(morpholin-4-yl)phenyl}prop-2-enamide
Synonyms	YH25448 GNS1480 CS-2767 YH-25448 YH 25448 GNS-1480 YH25448 YH-25448 GNS-1480 GNS1480. YH 25448 GNS 1480 LAZERTINIB Lazertinib Lazertinib(YH25448,GNS-1480) N-{5-[(4-{4-[(dimethylamino)methyl]-3-phenyl-1H-pyrazol-1-yl}pyrimidin-2-yl)amino]-4-methoxy-2-(morpholin-4-yl)phenyl}prop-2-enamide
CAS	1903008-80-9

GNS-1480 - Physico-chemical Properties

Molecular Formula	C30H34N8O3
Molar Mass	554.64
Density	1.27±0.1 g/cm3(Predicted)
Solubility	Soluble in DMSO
pKa	12.39±0.70(Predicted)
Storage Condition	-20℃
Use	Lazertinib, also known as YH-25448 and GNS-1480, is an oral active, highly potent, mutant-selective and irreversible EGFR Tyrosine-kinase inhibitors (TKIs) targets both the T790M mutation and activating EGFR mutations while sparing wild type-EGFR. YH25448 is expected to beneficial for the NSCLC patients with brain metastasis due to good blood brain barrier (BBB) penetration property as well as for the treatment of primary lung lesion and extracranial lesions. This study will be conducted to evaluate the safety, tolerability and efficacy of YH25448 in locally advanced or metastatic NSCLC patients with EGFR mutations.
In vitro study	Lazertinib was able to target EGFR activating mutants Del19, L858R and T790M, with a relatively small effect on wild-type EGFR. In NSCLC cell lines and in primary tumor cells (derived from patients with EGFR mutations), YH25448 inhibited the growth of cancer cells more effectively than osimertinib and significantly increased apoptosis of tumor cells. In the cell proliferation assay, the GI50 values of lazertinib for H1975 cells (L858R/T790M), PC9 cells (del19) and H2073 cells (wild-type EGFR) were 5 nM, 5 nM and 711 nM.
In vivo study	In vivo, YH25448 can cause non-significant, concentration-dependent tumor regression in subcutaneous and intracranial lesions when administered once daily to a mouse model transplanted with H1975 cells, without other abnormalities such as skin keratinization. The half-life of YH25448 in plasma is 5.9-6.8 hours, and the AUC 0-last ratio in tumor and plasma is 3.0-5.1. YH25448 can well cross the blood-brain barrier, and the concentration of cerebrospinal fluid can exceed the IC50 value of pEGFR inhibition. YH25448 also had good efficacy on tumor regression in a brain metastasis model with EGFR mutants.