Lapatinib
(Synonyms: 拉帕替尼; GW572016; GW2016) 目录号 : GC13608
Lapatinib是一种口服的双重EGFR和HER2酪氨酸激酶抑制剂，对HER2阳性乳腺癌具有显著疗效。Lapatinib对纯化的EGFR和HER2的半数抑制浓度（IC₅₀）值分别为10.2nM和9.8nM。
Cas No.:231277-92-2
Sample solution is provided at 25 µL, 10mM.
Lapatinib is an orally administered dual EGFR and HER2 tyrosine kinase inhibitor that has shown significant efficacy in the treatment of HER2-positive breast cancer[1]. The IC₅₀ values of Lapatinib against purified EGFR and HER2 are 10.2nM and 9.8nM, respectively[2].
In vitro, Lapatinib (50000, 10000, 2000, 400, 80, 0nM; 96h) and poziotinib combined with paclitaxel synergizes to inhibit the proliferation of ABCB1-overexpressing ovarian cancer cells in vitro[2]. Lapatinib (5μM; 24h) attenuated TOCP-induced ErbB2 expression in RSC96 cells[3]. Lapatinib (25, 50, 100, and 200μM; 24h) inhibits the proliferation of synovial fibroblasts in patients with arthritis[4]. Lapatinib (0-10μM; 24 and 48h) decreases the ACTH production and proliferation of corticotroph tumor cells[5].
In vivo, Lapatinib (25mg/kg; 4 days; p.o.) alleviates Tri-o-cresyl phosphate (TOCP)-induced axonal damage in the spinal cord of mouse[3]. Lapatinib (30mg/kg; 15 days; p.o.) reduces synovial hyperplasia and pannus formation in rats with arthritis and prevents the development of cartilage and bone destruction[6].
References:
[1] Raja Sharin RNFS, Khan J, Ibahim MJ, et al. Role of ErbB1 in the Underlying Mechanism of Lapatinib-Induced Diarrhoea: A Review. Biomed Res Int. 2022 Jun 28;2022:4165808.
[2] Rusnak DW, Lackey K, Affleck K, et al. The effects of the novel, reversible epidermal growth factor receptor/ErbB-2 tyrosine kinase inhibitor, GW2016, on the growth of human normal and tumor-derived cell lines in vitro and in vivo. Mol Cancer Ther. 2001 Dec;1(2):85-94.
[3] McCorkle JR, Gorski JW, Liu J, et al. Lapatinib and poziotinib overcome ABCB1-mediated paclitaxel resistance in ovarian cancer. PLoS One. 2021 Aug 4;16(8):e0254205.
[4] Xu HY, Sun YJ, Sun YY, et al. Lapatinib alleviates TOCP-induced axonal damage in the spinal cord of mouse. Neuropharmacology. 2021 May 15;189:108535.
[5] Kehribar DY, Emmungil H, Türkmen NB, et al. EGFR blocker lapatinib inhibits the synthesis of matrix metalloproteinases from synovial fibroblasts. Turk J Med Sci. 2022 Aug;52(4):1355-1361.
[6] Asari Y, Kageyama K, Sugiyama A, et al. Lapatinib decreases the ACTH production and proliferation of corticotroph tumor cells. Endocr J. 2019 Jun 28;66(6):515-522.
[7] Ozgen M, Koca SS, Karatas A, et al. Lapatinib ameliorates experimental arthritis in rats. Inflammation. 2015 Feb;38(1):252-9.
Lapatinib是一种口服的双重EGFR和HER2酪氨酸激酶抑制剂，对HER2阳性乳腺癌具有显著疗效[1]。Lapatinib对纯化的EGFR和HER2的半数抑制浓度（IC₅₀）值分别为10.2nM和9.8nM[2]。
体外实验中，Lapatinib（50000, 10000, 2000, 400, 80和0nM; 96小时）与泊齐替尼联合紫杉醇能够协同抑制ABCB1过表达的卵巢癌细胞的增殖[2]。Lapatinib（5μM; 24小时）能够减轻三邻甲酚磷酸酯（TOCP）诱导的RSC96细胞中ErbB2的表达[3]。Lapatinib（25, 50, 100和200μM; 24小时）能够抑制关节炎患者滑膜成纤维细胞的增殖[4]。Lapatinib（0-10μM; 24小时和48小时）能够降低促肾上腺皮质激素（ACTH）的产生并抑制促肾上腺皮质激素瘤细胞的增殖[5]。
体内实验中，Lapatinib（25mg/kg; 4天; 口服）能够减轻三邻甲酚磷酸酯（TOCP）诱导的小鼠脊髓轴突损伤[3]。Lapatinib（30mg/kg; 15天; 口服）能够减少关节炎大鼠的滑膜增生和血管翳形成，并预防软骨和骨骼破坏的发展[6]。
| Cell experiment [1]: | |
Cell lines | ovarian cancer cell lines TOV-21G and OVCAR-3 |
Preparation Method | Cells were seeded in white-walled 96-well microplates at a density of 3×10³ cells per well in 100μL growth media and incubated for 24h at 37°C, 5% CO₂ to allow cells to attach. Subsequently, the growth media was removed and replaced with fresh media containing serially diluted drugs of interest or blank media (for untreated controls), and incubated for 96h. We tested each drug alone and in combination with five serially diluted concentrations, and cell viability was measured using CellTiter-Glo 2.0. For each pair of drugs, every concentration was tested in combination in at least 3 independent experiments using a 6×6 matrix design. The percentage viability for each combination was calculated by dividing the drug-treated signals by the untreated signals and multiplying by 100. Paclitaxel (1000, 167, 28, 4.6, 0.77, 0nM) was tested in combination with Lapatinib (50000, 10000, 2000, 400, 80, 0nM) and poziotinib (12500, 4167, 1389, 463, 154, 0nM). Synergy for each drug combination was assessed using the synergyfinder package in R, with the percentage of viable cells relative to untreated control cells as the basis for evaluation. |
Reaction Conditions | 50000, 10000, 2000, 400, 80, 0nM; 96h |
Applications | Lapatinib and poziotinib combined with paclitaxel synergizes to inhibit the proliferation of ABCB1-overexpressing ovarian cancer cells in vitro. |
| Animal experiment [2]: | |
Animal models | male Balb/c mice, 8 weeks old and 20-25g |
Preparation Method | Seventy-six mice were divided into three groups: Tri-o-cresyl phosphate (TOCP) treatment (n=33); TOCP plus Lapatinib (LPT) treatment (n=33); vehicle treatment (n=10). Mice from TOCP-treated group were given a single dose of TOCP at 900mg/kg by gavage, while mice from TOCP plus Lapatinib-treated group were treated twice with Lapatinib dissolved in 10% sulfobutyl-β-cyclodextrin at a dose of 25mg/kg (p.o.), 4h before and 4 days after TOCP treatment. Mice from control group were given corresponding vehicles. Mice were examined daily for the signs of TOCP intoxication for 21 days. |
Dosage form | 25mg/kg; 4 days; p.o. |
Applications | Lapatinib alleviates Tri-o-cresyl phosphate (TOCP)-induced axonal damage in the spinal cord of mouse. |
References: | |
| Cas No. | 231277-92-2 | SDF | |
| 别名 | 拉帕替尼; GW572016; GW2016 | ||
| 化学名 | N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinazolin-4-amine | ||
| Canonical SMILES | CS(=O)(=O)CCNCC1=CC=C(O1)C2=CC3=C(C=C2)N=CN=C3NC4=CC(=C(C=C4)OCC5=CC(=CC=C5)F)Cl | ||
| 分子式 | C29H26ClFN4O4S | 分子量 | 581.06 |
| 溶解度 | ≥ 29.05mg/mL in DMSO | 储存条件 | Store at -20°C |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.721 mL | 8.605 mL | 17.2099 mL |
| 5 mM | 0.3442 mL | 1.721 mL | 3.442 mL |
| 10 mM | 0.1721 mL | 0.8605 mL | 1.721 mL |
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| % DMSO % % Tween 80 % saline | ||||||||||
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