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| ln Vitro |
Lazatinib mesylate (0.1–1000 nM; 3 days) inhibited the viability of Ba/F3 cells expressing various rare EGFR mutations, with IC50 values ranging from 3.5 nM to 108.3 nM[1]. Lazatinib mesylate (10 nM (YUO-139 PDOs); 100 nM (YU-1092 PDCs); 72 hours) upregulated EGFR expression on the surface of EGFR G719S mutant YUO-139 patient-derived organoids and EGFR L861Q mutant YU-1092 patient-derived cells after 72 hours of treatment[1]. Lazatinib mesylate (0.001–10 μM; 72 hours) inhibited the viability of EGFR mutant non-small cell lung cancer (NSCLC) cell lines after 72 hours of incubation[2]. Lazatinib mesylate (0.01–3.0 μM; 7 days, with medium changed every 72 hours) inhibited the long-term proliferation of PC-9 EGFR mutant NSCLC cells in a concentration-dependent manner over 7 days, but failed to completely inhibit cell growth at the tested concentrations [2]. Lazatinib mesylate (100 nM; 4 hours; 72 hours) inhibited the phosphorylation of EGFR, ERK, and AKT in PC-9 and HCC4011 EGFR mutant NSCLC cells, but its inhibitory effect on ERK and AKT disappeared after 72 hours [2]. Lazatinib mesylate (100 nM; 48 hours) upregulated the expression of the anti-apoptotic protein MCL-1 in PC-9, HCC4011, and H1975 EGFR mutant non-small cell lung cancer cells [2]. Lazazinib mesylate (100 μM; 72 hours) showed considerable cytotoxicity to drug-sensitive parental cancer cell lines (HepG2, KB, S1, HEK293/Vector) and their multidrug-resistant (MDR) sublines overexpressing ABCB1 or ABCG2. It reduced the IC50 values of vincristine (A), doxorubicin (A), mitoxantrone and topotecan, but had no significant effect on cisplatin [3]. Lazazinib mesylate (0.1-1 μM; 24 hours) did not induce neurite rupture in primary cultured dorsal root ganglion (DRG) neurons of the L3, L4 and L5 segments of adult mice [4].
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| ln Vivo |
Lazatinib mesylate (10 mg/kg; orally; once daily; days 27–29) achieved tumor growth inhibition rates of 26.3% and 141%, respectively, in Ba/F3 EGFRG719S and YUO-139 EGFRG719S non-small cell lung cancer xenograft models [1]. Lazatinib mesylate (10 mg/kg; orally; once daily; for 19 consecutive days) failed to inhibit tumor growth in gefitinib-resistant non-small cell lung cancer EGFRL861Q YU-1092 xenograft models [1]. Lazatinib mesylate (10 mg/kg; orally; once daily; administered up to day 29) induced initial tumor regression in EGFR-TKI-resistant non-small cell lung cancer YHIM-1008 EGFRG719C/S768I xenograft models, but failed to achieve durable control [1]. Lazatinib mesylate (3 mg/kg; once daily for 31 days) exhibited transient antitumor activity against PC-9 CDX tumors, which relapsed within 3 weeks of treatment initiation [2]. Lazatinib mesylate (10 mg/kg; orally; once every 3 days for 6 doses) failed to inhibit the growth of ABCB1-overexpressing HepG2/adr xenografts. However, when used in combination with doxorubicin, it effectively reversed ABCB1-mediated multidrug resistance, significantly reduced tumor volume and weight, and no toxicity was observed [3]. Lazatinib mesylate (1 mM, 20 μL; plantar injection; single dose) induced TRPA1-dependent pain-like behavior in male C57BL/6J mice, with a mean licking and biting duration of 58.91 seconds over 15 minutes [4].
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| Cell Assay |
Cell viability assay [1]
Cell Types: Ba/F3 cells expressing rare mutations of EGFR G719S, S768I, G719A/S768I, L861Q, G719S/S768I and S768I/L858R Tested Concentrations: 0.1-1000 nM Incubation Duration: 3 days Experimental Results: In EGFR G719S Ba/F3 cells, the IC50 was 3.5 nM, and cell viability was inhibited. In EGFR S768I Ba/F3 cells, the IC50 was 108.3 nM, and cell viability was inhibited. In EGFR G719A/S768I Ba/F3 cells, the IC50 value for inhibiting cell viability was 36.8 nM. In EGFR L861Q Ba/F3 cells, the IC50 value for inhibiting cell viability was 13.9 nM. In EGFR G719S/S768I Ba/F3 cells, the IC50 value for inhibiting cell viability was 21.9 nM. In EGFR S768I/L858R Ba/F3 cells, the IC50 value for inhibiting cell viability was 7.2 nM. Cell viability assay [2] Cell Types: PC-9, HCC4011, H1975, PC-9GXR, KPP-03, HCC827, HCC4006 (EGFR mutant non-small cell lung cancer cell lines) Tested Concentrations: 0.001-10 μM Incubation Duration: 72 hours Experimental Results: Cell viability was inhibited in all seven cell lines, with IC50 values of: 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. It exhibits the highest sensitivity in HCC827 and HCC4006, and the lowest sensitivity in KPP-03. Cytotoxicity assay [3] Cell Types: ABCB1 overexpressing resistant cells (KBv200, HepG2/adr, HEK293/ABCB1), ABCG2 overexpressing resistant cells (S1-MI-80, HEK293/ABCG2) and their parental sensitive cells Tested Concentrations: 0.0625-0.25 μM Incubation Duration: 72 hours Experimental Results: In ABCB1 overexpressing cells, the IC50 value of vincristine (A) decreased by up to 25.21 times, the IC50 value of doxorubicin (A) decreased by up to 14.82 times, and the IC50 value of paclitaxel decreased by up to 15.90 times. In ABCG2-overexpressing cells, the IC50 values of mitoxantrone decreased by 8.97-fold, and those of topotecan decreased by 11.94-fold. In parental sensitive cells, the IC50 values of the substrate drugs did not change significantly; similarly, the IC50 values of the non-substrate cisplatin did not change significantly in sensitive or multidrug-resistant cells. |
| Animal Protocol |
Animal/Disease Models:nu/nu (6-week-old females) [1]
Doses: 10 mg/kg Route of Administration: Oral; once daily; 29 days Experimental Results: Induced a tumor growth inhibition rate (TGI) of 141%. Compared with the combination of lazatinib and amivastatin, the duration of efficacy was shorter, and tumor recurrence was observed in some treated mice after drug withdrawal. Animal/Disease Models:Athymic nude mice (4-6 weeks old, 16-20 g, subcutaneously inoculated with HepG2/adr cells overexpressing ABCB1) [3] Doses: 10 mg/kg (monotherapy); 10 mg/kg (combined with doxorubicin) Route of Administration: Oral; once every 3 days; for a total of 6 times Experimental Results: No reduction in tumor volume or weight was observed in the monotherapy group compared with the saline control group. Tumor volume and weight were significantly reduced in the monotherapy group compared with the saline group and the doxorubicin monotherapy group. No significant change in mouse weight was observed, indicating good tolerability (monotherapy group and combination therapy group). Animal/Disease Models:C57BL/6J (5-6 weeks old, male) [4] Doses: 1 mM, 20 μL Route of Administration: Plantar injection; single dose Experimental Results: Compared with the vector control group, the average licking/biting time within 15 minutes increased to 58.91 seconds (6.832 seconds). Compared with the total licking/biting time of the pre-injected vector group (105.6 seconds), pre-injection of the TRPA1 antagonist HC-030031 reduced the total licking/biting time to 46.11 seconds. |
| References |
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| Molecular Formula |
C31H38N8O6S
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|---|---|
| Molecular Weight |
650.75
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| CAS # |
2247995-37-3
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| Related CAS # |
Lazertinib; Lazertinib mesylate hydrate
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| Appearance |
White to off-white solid
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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
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| Synonyms |
YH25448 mesylate; GNS-1480 mesylate
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: 请将本产品存放在密封保护的环境中，避免受潮。 |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~153.67 mM; with sonication)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5367 mL | 7.6834 mL | 15.3669 mL | |
| 5 mM | 0.3073 mL | 1.5367 mL | 3.0734 mL | |
| 10 mM | 0.1537 mL | 0.7683 mL | 1.5367 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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