Lazertinib | YH-25448 | GNS-1480 | CAS#1903008-80-9 | EGFR inhibitor

MedKoo Cat#: 206860 | Name: Lazertinib

Description:

WARNING: This product is for research use only, not for human or veterinary 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.

Chemical Structure

Lazertinib

CAS#1903008-80-9 (free base)

Theoretical Analysis

MedKoo Cat#: 206860

Name: Lazertinib

CAS#: 1903008-80-9 (free base)

Chemical Formula: C30H34N8O3

Exact Mass: 554.2754

Molecular Weight: 554.66

Elemental Analysis: C, 64.96; H, 6.18; N, 20.20; O, 8.65

Price and Availability

Size	Price	Availability
10mg	USD 120.00	Ready to ship
50mg	USD 350.00	Ready to ship
100mg	USD 550.00	Ready to ship
200mg	USD 950.00	Ready to ship
500mg	USD 1,950.00	Ready to ship
1g	USD 2,950.00	Ready to ship

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Related CAS #

2247995-37-3 (mesylate) 1903008-80-9 (free base) 2247995-38-4 (HCl) 2411549-88-5 (mesylate hydrate)

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).

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#S9S01C10

QC Data

View QC data: current batch, Lot#S9S01C10

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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	mg/mL	mM
Solubility
	DMSO	6.5	11.72

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

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:

In vivo protocol:

1: Passaro A, Wang J, Wang Y, Lee SH, Melosky B, Shih JY, Wang J, Azuma K, Juan- Vidal O, Cobo M, Felip E, Girard N, Cortot AB, Califano R, Cappuzzo F, Owen S, Popat S, Tan JL, Salinas J, Tomasini P, Gentzler RD, William WN Jr, Reckamp KL, Takahashi T, Ganguly S, Kowalski DM, Bearz A, MacKean M, Barala P, Bourla AB, Girvin A, Greger J, Millington D, Withelder M, Xie J, Sun T, Shah S, Diorio B, Knoblauch RE, Bauml JM, Campelo RG, Cho BC; MARIPOSA-2 Investigators. Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study. Ann Oncol. 2024 Jan;35(1):77-90. doi: 10.1016/j.annonc.2023.10.117. Epub 2023 Oct 23. PMID: 37879444. 2: Cho BC, Lu S, Felip E, Spira AI, Girard N, Lee JS, Lee SH, Ostapenko Y, Danchaivijitr P, Liu B, Alip A, Korbenfeld E, Mourão Dias J, Besse B, Lee KH, Xiong H, How SH, Cheng Y, Chang GC, Yoshioka H, Yang JC, Thomas M, Nguyen D, Ou SI, Mukhedkar S, Prabhash K, D'Arcangelo M, Alatorre-Alexander J, Vázquez Limón JC, Alves S, Stroyakovskiy D, Peregudova M, Şendur MAN, Yazici O, Califano R, Gutiérrez Calderón V, de Marinis F, Passaro A, Kim SW, Gadgeel SM, Xie J, Sun T, Martinez M, Ennis M, Fennema E, Daksh M, Millington D, Leconte I, Iwasawa R, Lorenzini P, Baig M, Shah S, Bauml JM, Shreeve SM, Sethi S, Knoblauch RE, Hayashi H; MARIPOSA Investigators. Amivantamab plus Lazertinib in Previously Untreated EGFR-Mutated Advanced NSCLC. N Engl J Med. 2024 Oct 24;391(16):1486-1498. doi: 10.1056/NEJMoa2403614. Epub 2024 Jun 26. PMID: 38924756. 3: Cho BC, Felip E, Hayashi H, Thomas M, Lu S, Besse B, Sun T, Martinez M, Sethi SN, Shreeve SM, Spira AI. MARIPOSA: phase 3 study of first-line amivantamab + lazertinib versus osimertinib in EGFR-mutant non-small-cell lung cancer. Future Oncol. 2022 Feb;18(6):639-647. doi: 10.2217/fon-2021-0923. Epub 2021 Dec 16. PMID: 34911336. 4: Cho BC, Ahn MJ, Kang JH, Soo RA, Reungwetwattana T, Yang JC, Cicin I, Kim DW, Wu YL, Lu S, Lee KH, Pang YK, Zimina A, Fong CH, Poddubskaya E, Sezer A, How SH, Danchaivijitr P, Kim Y, Lim Y, An T, Lee H, Byun HM, Zaric B. Lazertinib Versus Gefitinib as First-Line Treatment in Patients With EGFR-Mutated Advanced Non-Small-Cell Lung Cancer: Results From LASER301. J Clin Oncol. 2023 Sep 10;41(26):4208-4217. doi: 10.1200/JCO.23.00515. Epub 2023 Jun 28. PMID: 37379502. 5: Felip E, Cho BC, Gutiérrez V, Alip A, Besse B, Lu S, Spira AI, Girard N, Califano R, Gadgeel SM, Yang JC, Yamamoto S, Azuma K, Kim YJ, Lee KH, Danchaivijitr P, Ferreira CG, Cheng Y, Sendur MAN, Chang GC, Wang CC, Prabhash K, Shinno Y, Stroyakovskiy D, Paz-Ares L, Rodriguez-Cid JR, Martin C, Campelo MRG, Hayashi H, Nguyen D, Tomasini P, Gottfried M, Dooms C, Passaro A, Schuler M, Gelatti ACZ, Owen S, Perdrizet K, Ou SI, Curtin JC, Zhang J, Gormley M, Sun T, Panchal A, Ennis M, Fennema E, Daksh M, Sethi S, Bauml JM, Lee SH. Amivantamab plus lazertinib versus osimertinib in first-line EGFR-mutant advanced non-small-cell lung cancer with biomarkers of high-risk disease: a secondary analysis from MARIPOSA. Ann Oncol. 2024 Sep;35(9):805-816. doi: 10.1016/j.annonc.2024.05.541. Epub 2024 Jun 26. PMID: 38942080. 6: Cho BC, Kim DW, Spira AI, Gomez JE, Haura EB, Kim SW, Sanborn RE, Cho EK, Lee KH, Minchom A, Lee JS, Han JY, Nagasaka M, Sabari JK, Ou SI, Lorenzini P, Bauml JM, Curtin JC, Roshak A, Gao G, Xie J, Thayu M, Knoblauch RE, Park K. Amivantamab plus lazertinib in osimertinib-relapsed EGFR-mutant advanced non- small cell lung cancer: a phase 1 trial. Nat Med. 2023 Oct;29(10):2577-2585. doi: 10.1038/s41591-023-02554-7. Epub 2023 Sep 14. PMID: 37710001; PMCID: PMC10579096. 7: Leighl NB, Akamatsu H, Lim SM, Cheng Y, Minchom AR, Marmarelis ME, Sanborn RE, Chih-Hsin Yang J, Liu B, John T, Massutí B, Spira AI, Lee SH, Wang J, Li J, Liu C, Novello S, Kondo M, Tamiya M, Korbenfeld E, Moskovitz M, Han JY, Alexander M, Joshi R, Felip E, Voon PJ, Danchaivijitr P, Hsu PC, Silva Melo Cruz FJ, Wehler T, Greillier L, Teixeira E, Nguyen D, Sabari JK, Qin A, Kowalski D, Şendur MAN, Xie J, Ghosh D, Alhadab A, Haddish-Berhane N, Clemens PL, Lorenzini P, Verheijen RB, Gamil M, Bauml JM, Baig M, Passaro A; PALOMA-3 Investigators. Subcutaneous Versus Intravenous Amivantamab, Both in Combination With Lazertinib, in Refractory Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer: Primary Results From the Phase III PALOMA-3 Study. J Clin Oncol. 2024 Oct 20;42(30):3593-3605. doi: 10.1200/JCO.24.01001. Epub 2024 Jun 10. PMID: 38857463; PMCID: PMC11469630.