WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H206860
CAS#: 1903008-80-9 (free base)
Description: 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.
Hodoodo Cat#: H206860
Name: Lazertinib
CAS#: 1903008-80-9 (free base)
Chemical Formula: C30H34N8O3
Exact Mass: 554.28
Molecular Weight: 554.660
Elemental Analysis: C, 64.96; H, 6.18; N, 20.20; O, 8.65
Related CAS #: 2411549-88-5 (mesylate hydrate) 1903008-80-9 (free base)
Synonym: Lazertinib; YH-25448; YH 25448; YH25448; GNS-1480; GNS 1480; GNS1480.
IUPAC/Chemical 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
InChi Key: RRMJMHOQSALEJJ-UHFFFAOYSA-N
InChi Code: InChI=1S/C30H34N8O3/c1-5-28(39)32-23-17-24(26(40-4)18-25(23)37-13-15-41-16-14-37)33-30-31-12-11-27(34-30)38-20-22(19-36(2)3)29(35-38)21-9-7-6-8-10-21/h5-12,17-18,20H,1,13-16,19H2,2-4H3,(H,32,39)(H,31,33,34)
SMILES Code: C=CC(NC1=CC(NC2=NC=CC(N3N=C(C4=CC=CC=C4)C(CN(C)C)=C3)=N2)=C(OC)C=C1N5CCOCC5)=O
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info: Currently-available EGFR TKIs are ineffective for the treatment of brain metastases (BrM) due to limited blood-brain barrier (BBB) penetration. YH25448 is a potent, highly mutant-selective and irreversible 3rd generation EGFR TKI that is able to penetrate the BBB, and targets both the T790M mutation and activating EGFR mutations while sparing wild type (wt).
| Biological target: | Lazertinib (YH25448) is a potent, highly mutant-selective, blood-brain barrier permeable, orally available and irreversible third-generation EGFR tyrosine kinase inhibitor. |
| In vitro activity: | To investigate whether YH25448 could effectively block EGFR and its downstream signaling pathways, this study treated EGFR-mutant lung cancer cells with YH25448 at different concentrations for 6 hours (Fig. 2A). YH25448 significantly suppressed EGFR downstream signaling, including phospho-EGFR (p-EGFR), phospho-AKT (p-AKT), and phospho-ERK (p-ERK). The cell viability data showed that YH25448 effectively and significantly inhibited the proliferation of Del19- and/or T790M-mutant NSCLC cells at lower concentrations than those needed to inhibit cells with other EGFR-TKIs (IC50 values ranging from 1.9 to 12.4 nmol/L against PC9, YU-1098, PC9GR, YU-1153, and YU-1150), while showing much less activity against cells with WT EGFR (H2291; Fig. 2B). Treatment with YH25448 induced the apoptosis in EGFR-mutant cell lines, as demonstrated by an increase in the cleaved Bim-EL protein or activated caspase-3/7, in H1975 and PC9 cells (Supplementary Fig. S1B and S1C). Reference: Clin Cancer Res. 2019 Apr 15;25(8):2575-2587. https://clincancerres.aacrjournals.org/content/25/8/2575.long |
| In vivo activity: | To determine whether YH25448 is effective in vivo, H1975 tumor-bearing mice were randomly grouped and dosed orally, once daily, with the vehicle and 1, 3, and 10 mg/kg YH25448 or osimertinib for a period of 13 days. YH25448 significantly shrunk the tumor volume within a very short period after the first administration at doses as low as 3 and 10 mg/kg/day (Fig. 2C). After 13-day treatment at a dose of 3 mg/kg treatment, YH25448 suppressed 86.85% of the tumor growth compared with only 7.24% tumor regression in the osimertinib group. Surprisingly, near complete tumor regression (90%) was achieved at a higher dose, 10 mg/kg, without any body weight changes (Supplementary Fig. S1D). Reference: Clin Cancer Res. 2019 Apr 15;25(8):2575-2587. https://clincancerres.aacrjournals.org/content/25/8/2575.long |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 6.5 | 11.72 |
The following data is based on the product molecular weight 554.66 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Yun J, Hong MH, Kim SY, Park CW, Kim S, Yun MR, Kang HN, Pyo KH, Lee SS, Koh JS, Song HJ, Kim DK, Lee YS, Oh SW, Choi S, Kim HR, Cho BC. YH25448, an Irreversible EGFR-TKI with Potent Intracranial Activity in EGFR Mutant Non-Small Cell Lung Cancer. Clin Cancer Res. 2019 Apr 15;25(8):2575-2587. doi: 10.1158/1078-0432.CCR-18-2906. Epub 2019 Jan 22. PMID: 30670498. |
| In vitro protocol: | 1. Yun J, Hong MH, Kim SY, Park CW, Kim S, Yun MR, Kang HN, Pyo KH, Lee SS, Koh JS, Song HJ, Kim DK, Lee YS, Oh SW, Choi S, Kim HR, Cho BC. YH25448, an Irreversible EGFR-TKI with Potent Intracranial Activity in EGFR Mutant Non-Small Cell Lung Cancer. Clin Cancer Res. 2019 Apr 15;25(8):2575-2587. doi: 10.1158/1078-0432.CCR-18-2906. Epub 2019 Jan 22. PMID: 30670498. |
| In vivo protocol: | 1. Yun J, Hong MH, Kim SY, Park CW, Kim S, Yun MR, Kang HN, Pyo KH, Lee SS, Koh JS, Song HJ, Kim DK, Lee YS, Oh SW, Choi S, Kim HR, Cho BC. YH25448, an Irreversible EGFR-TKI with Potent Intracranial Activity in EGFR Mutant Non-Small Cell Lung Cancer. Clin Cancer Res. 2019 Apr 15;25(8):2575-2587. doi: 10.1158/1078-0432.CCR-18-2906. Epub 2019 Jan 22. PMID: 30670498. |
