Lazertinib mesylate hydrate
Based on 3 publication(s) in Google Scholar
Lazertinib (YH25448; GNS-1480) mesylate hydrate is an orally active, blood-brain barrier permeable third-generation EGFR tyrosine kinase inhibitor, as well as an ABCB1/ABCG2 inhibitor and a TRPA1 activator. Lazertinib mesylate hydrate exhibits IC50 values of 0.4 mM and 0.2 mM against human ABCB1 and ABCG2, respectively. By inhibiting mutant EGFR signaling, EGFR phosphorylation and the downstream ERK/AKT pathway, as well as upregulating surface expression of EGFR/MET, Lazertinib mesylate hydrate induces cell cycle arrest, apoptosis, spontaneous calcium responses, hyperexcitability of dorsal root ganglion (DRG) neurons, and TRPA1-dependent pain-like behaviors. Lazertinib mesylate hydrate competitively binds to the substrate-binding sites of ABCB1/ABCG2, stimulates their ATPase activity without altering their expression or plasma membrane localization, thereby enhancing ADCC activity, acting as a chemosensitizer, and reversing ABCB1-mediated multidrug resistance. It exerts antitumor activity as a single agent or in combination with other drugs. Lazertinib mesylate hydrate is applicable to research related to non-small cell lung cancer, multidrug-resistant cancers, and paresthesia.
For research use only. We do not sell to patients.
- CAS No.: 2411549-88-5
- Formula: C31H40N8O7S
- Molecular Weight:668.76
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
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Publications Citing Use of MedChemExpress (MCE) Lazertinib mesylate hydrate
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Biological Activity
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EGFRT790M |
TRPA1 |
Lazertinib mesylate hydrate (0.1-1000 nM; 3 d) inhibits the viability of Ba/F3 cells expressing various rare EGFR mutations, with IC50 values ranging from 3.5 nM to 108.3 nM[1].
Lazertinib mesylate hydrate (10 nM (YUO-139 PDOs); 100 nM (YU-1092 PDCs); 72 h) upregulates EGFR expression on the surface of EGFRG719S-mutant YUO-139 patient-derived organoids and EGFRL861Q-mutant YU-1092 patient-derived cells after 72 h of treatment[1].
Lazertinib mesylate hydrate (0.001-10 μM; 72 h) inhibits the viability of EGFR-mutant non-small cell lung cancer (NSCLC) cell lines after 72 h of incubation[2].
Lazertinib mesylate hydrate (0.01-3.0 μM; 7 d, medium changed every 72 h) inhibits the long-term proliferation of PC-9 EGFR-mutant NSCLC cells in a concentration-dependent manner within 7 days, but fails to achieve complete growth inhibition at the tested concentrations[2].
Lazertinib mesylate hydrate (100 nM; 4 h; 72 h) inhibits the phosphorylation of EGFR, ERK and AKT in PC-9 and HCC4011 EGFR-mutant NSCLC cells, but its inhibitory effects on ERK and AKT disappear by 72 h[2].
Lazertinib mesylate hydrate (100 nM; 48 h) upregulates the expression of the anti-apoptotic protein MCL-1 in PC-9, HCC4011 and H1975 EGFR-mutant non-small cell lung cancer cells[2].
Lazertinib mesylate hydrate (100 μM; 72 h) exhibits equivalent cytotoxicity in drug-sensitive parental cancer cell lines (HepG2, KB, S1, HEK293/Vector) and their multidrug-resistant (MDR) sublines with overexpressed ABCB1 or ABCG2. It reduces the IC50 values of Vincristine (HY-N0488A), Doxorubicin (HY-15142A), Mitoxantrone (HY-13502), and Topotecan (HY-13768), respectively, but shows no significant effect on Cisplatin (HY-17394)[3].
Lazertinib mesylate hydrate (0.1-1 μM; 24 h) does not induce neurite fragmentation in primary cultured dorsal root ganglion (DRG) neurons from the L3, L4 and L5 segments of adult mice[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Ba/F3 cells expressing EGFR G719S, S768I, G719A/S768I, L861Q, G719S/S768I, and S768I/L858R uncommon mutations
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Concentration:0.1-1000 nM
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Incubation Time:3 days
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Result:Inhibited cell viability with an IC50 of 3.5 nM in EGFR G719S Ba/F3 cells. Inhibited cell viability with an IC50 of 108.3 nM in EGFR S768I Ba/F3 cells. Inhibited cell viability with an IC50 of 36.8 nM in EGFR G719A/S768I Ba/F3 cells. Inhibited cell viability with an IC50 of 13.9 nM in EGFR L861Q Ba/F3 cells. Inhibited cell viability with an IC50 of 21.9 nM in EGFR G719S/S768I Ba/F3 cells. Inhibited cell viability with an IC50 of 7.2 nM in EGFR S768I/L858R Ba/F3 cells.
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Cell Line:PC-9, HCC4011, H1975, PC-9GXR, KPP-03, HCC827, HCC4006 (EGFR-mutant non-small cell lung cancer cell lines)[2]
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Concentration:0.001-10 μM
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Incubation Time:72 h
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Result:Inhibited cell viability in all seven cell lines, with IC50 values: PC-9: 0.103 μM; HCC4011: 0.161 μM; H1975: 4.074 μM; PC-9GXR: 1.379 μM; KPP-03: >10.0 μM; HCC827: <0.001 μM; HCC4006: 0.002 μM. Showed highest sensitivity in HCC827 and HCC4006, and lowest sensitivity in KPP-03.
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Cell Line:ABCB1-overexpressing MDR cells (KBv200, HepG2/adr, HEK293/ABCB1), ABCG2-overexpressing MDR cells (S1-MI-80, HEK293/ABCG2), and their parental sensitive cells
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Concentration:0.0625-0.25 μM
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Incubation Time:72 h
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Result:Reduced the IC50 of vincristine (HY-N0488A) by up to 25.21-fold, doxorubicin (HY-15142A) by up to 14.82-fold, and paclitaxel by up to 15.90-fold in ABCB1-overexpressing cells. Reduced the IC50 of mitoxantrone (HY-13502) by up to 8.97-fold and topotecan (HY-13768) by up to 11.94-fold in ABCG2-overexpressing cells. Did not significantly alter the IC50 values of substrate drugs in parental sensitive cells, or the IC50 of non-substrate cisplatin (HY-17394) in either sensitive or MDR cells.
Mesylate of Lazertinib (10 mg/kg; p.o.; once daily; for 19 consecutive days) mesylate hydrate fails to inhibit tumor growth in the gefitinib (HY-50895)-resistant non-small cell lung cancer EGFRL861Q YU-1092 xenograft model[1].
Mesylate of Lazertinib (10 mg/kg; p.o.; once daily; administered until day 29) mesylate hydrate induces initial tumor regression but fails to achieve durable control in the EGFR-TKI-resistant non-small cell lung cancer YHIM-1008 EGFRG719C/S768I xenograft model[1].
Mesylate of Lazertinib (3 mg/kg; daily; for 31 consecutive days) mesylate hydrate exerts transient anti-tumor activity in PC-9 CDX tumors, with the tumors exhibiting regrowth within 3 weeks after the initiation of treatment[2].
Mesylate of Lazertinib (10 mg/kg; p.o.; once every 3 days; 6 doses total) mesylate hydrate fails to inhibit the growth of ABCB1-overexpressing HepG2/adr xenografts. However, when combined with Doxorubicin (HY-15142A), it effectively reverses ABCB1-mediated multidrug resistance, significantly reduces tumor volume and weight, with no observed toxicity[3].
Mesylate of Lazertinib (1 mM, 20 μL; plantar injection; single administration) mesylate hydrate induces TRPA1-dependent pain-like behavior in male C57BL/6J mice, with an average licking and biting duration of 58.91 seconds within 15 minutes[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:nu/nu mice (6-week-old female)[1]
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Dosage:10 mg/kg
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Administration:p.o.; daily; 29 days
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Result:Induced a 141% tumor growth inhibition (TGI). Showed less durable responses than the lazertinib-amivantamab combination, with tumor regrowth observed in a subset of treated mice after treatment discontinuation.
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Animal Model:Athymic nude mice (4-6 weeks old, 16-20 g, subcutaneous inoculation with ABCB1-overexpressing HepG2/adr cells)[3]
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Dosage:10 mg/kg (monotherapy); 10 mg/kg (combination with doxorubicin)
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Administration:p.o.; q3d; 6 doses
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Result:Did not reduce tumor volume or weight relative to saline control (monotherapy). Produced a remarkable decrease in tumor volume and tumor weight relative to saline group and doxorubicin-alone group (combination with doxorubicin). Showed no obvious changes in mouse body weight, indicating good tolerability (monotherapy and combination groups).
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Animal Model:C57BL/6J mice (5- to 6-week-old, male)[4]
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Dosage:1 mM, 20 μL
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Administration:intraplantar; single dose
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Result:Increased average licking/biting time to 58.91 seconds over 15 minutes, compared to 6.832 seconds in vehicle-treated mice. Reduced total licking/biting time to 46.11 seconds when preinjected with TRPA1 antagonist HC-030031, compared to 105.6 seconds in vehicle-preinjected group.
Chemical Information
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CAS No. 2411549-88-5
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Molecular Weight 668.76
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Formula C31H40N8O7S
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SMILES
O=C(NC1=CC(NC2=NC=CC(N3N=C(C(CN(C)C)=C3)C4=CC=CC=C4)=N2)=C(C=C1N5CCOCC5)OC)C=C.O=S(O)(C)=O.O
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Synonyms
YH25448 mesylate hydrate; GNS-1480 mesylate hydrate
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Publications (3)
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Journal Impact Factor
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Most Recent
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Cancer Res
Enozertinib is a Selective, Brain-penetrant EGFR inhibitor for Treating Non-small Cell Lung Cancers with EGFR Exon 20 and Atypical Mutations. [Abstract]2025 Nov 6. PMID: 41196054 -
Drug Discov Ther
Solid phase extraction and high-performance liquid chromatographic determination of lazertinib in human plasma. [Abstract]2025 Oct 17. PMID: 41110965 -
Purity & Documentation
References
[1]. Oh SY, et al. The potential of lazertinib and amivantamab combination therapy as a treatment strategy for uncommon EGFR-mutated NSCLC. Cell Rep Med. 2025;6(2):101929. [Content Brief]
[2]. Matsui Y, et al. Initial AXL and MCL-1 inhibition contributes to abolishing lazertinib tolerance in EGFR-mutant lung cancer cells. Cancer Sci. 2024;115(10):3333-3345. [Content Brief]
[4]. Kim H, et al. EGFR Tyrosine Kinase Inhibitor Lazertinib Activates a Subset of Mouse Sensory Neurons Via TRPA1. J Pain. 2024;25(5):104435. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Lazertinib mesylate hydrate Related Classifications
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