Epertinib (S-22611)
(Synonyms: 艾培替尼,S-22611) 目录号 : GC33048
Epertinib (S-22611) (S-22611) 是一种有效的、口服的、可逆的、选择性的 EGFR、HER2 和 HER4 酪氨酸激酶抑制剂，IC50 分别为 1.48 nM、7.15 nM 和 2.49 nM。 Epertinib (S-22611) 显示出有效的抗肿瘤活性。
Cas No.:908305-13-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Epertinib is a potent, oral, reversible, and selective tyrosine kinase inhibitor of EGFR, HER2 and HER4, with IC50s of 1.48 nM, 7.15 nM and 2.49 nM, respectively; Epertinib shows potent antitumor activity.
Epertinib (S-222611) is a potent, oral, reversible, and selective tyrosine kinase inhibitor of EGFR, HER2 and HER4, with IC50s of 1.48 nM, 7.15 nM and 2.49 nM, respectively, and shows no effect on KDR, IGF1R, SRC, KIT, and PDGFRβ (IC50, >10000 nM). Epertinib inhibits relative phosphorylation of EGFR and HER2 in NCI-N87 cells, with IC50s of 4.5 and 1.6 nM, respectively. Furthermore, Epertinib exhibits inhibitory activity against the growth of cancer cell lines expressing EGFR and/or HER2, with IC50s of 8.3 nM (NCI-N87 (stomach)), 9.9 nM (BT-474 (breast)), and 14 nM (SK-BR-3 (breast))[1]. Epertinib also inhibits MDA-MB-361 cell growth, with an IC50 of 26.5 nM[2].
Epertinib shows antitumor activity in nude mice bearing NCI-N87 xenograft via oral administration for 21 days, with an ED50 of 10.2 mg/kg. Epertinib (50 mg/kg, p.o.) is four times more potent activity than lapatinib and completely inhibits the growth of cancer cells in mice[1]. Epertinib (50 mg/kg, p.o.) markedly reduces the brain tumor volume in the breast cancer intraventricular injection mouse brain metastasis model (IVM)[2].
[1]. Tanaka H, et al. Preclinical antitumor activity of S-222611, an oral reversible tyrosine kinase inhibitor of epidermal growth factor receptor and human epidermal growth factor receptor 2. Cancer Sci. 2014 Aug;105(8):1040-8. [2]. Tanaka Y, et al. Distribution analysis of epertinib in brain metastasis of HER2-positive breast cancer by imaging mass spectrometry and prospect for antitumor activity. Sci Rep. 2018 Jan 10;8(1):343.
| Cas No. | 908305-13-5 | SDF | |
| 别名 | 艾培替尼,S-22611 | ||
| Canonical SMILES | CC#C/C(C1=CC2=C(NC3=CC=C(OCC4=CC=CC(F)=C4)C(Cl)=C3)N=CN=C2C=C1)=N\OC[C@@H]5NCCOC5 | ||
| 分子式 | C30H27ClFN5O3 | 分子量 | 560.02 |
| 溶解度 | Soluble in DMSO | 储存条件 | 4°C, protect from light |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7857 mL | 8.9283 mL | 17.8565 mL |
| 5 mM | 0.3571 mL | 1.7857 mL | 3.5713 mL |
| 10 mM | 0.1786 mL | 0.8928 mL | 1.7857 mL |
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Distribution analysis of Epertinib in brain metastasis of HER2-positive breast cancer by imaging mass spectrometry and prospect for antitumor activity
Sci Rep 2018 Jan 10;8(1):343.PMID:29321587DOI:10.1038/s41598-017-18702-2.
Epertinib (S-222611) is a potent, reversible, and selective tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR), human EGFR2 (HER2), and human EGFR4. We developed experimental brain metastasis models by intraventricular injection (intraventricular injection mouse model; IVM) of HER2-positive breast cancer (MDA-MB-361-luc-BR2/BR3) or T790M-EGFR-positive lung cancer (NCI-H1975-luc) cells. After a single oral administration, Epertinib and lapatinib concentrations in brain metastatic regions were analyzed by quantitative imaging mass spectrometry. In the NCI-H1975 lung cancer IVM, the concentration of Epertinib in brain metastasis was comparable to that of lapatinib. However, in the MDA-MB-361 breast cancer IVM, the concentration of Epertinib in brain metastasis was >10 times higher than that of lapatinib. Furthermore, the Epertinib tumor-to-normal brain ratio was ~4 times higher than that of lapatinib. Blood-tumor barrier (BTB) permeability was assessed in each brain metastatic region. In the lung cancer model, fluorescently labeled dextran was more highly detected in brain metastatic regions than in brain parenchyma. However, in breast cancer models, dextran fluorescence intensity in brain metastatic regions and brain parenchyma were comparable, suggesting that the BTB remained largely intact. Epertinib would be promised as a therapeutic agent for HER2-positive breast cancer with brain metastasis.
An extended phase Ib study of Epertinib, an orally active reversible dual EGFR/HER2 tyrosine kinase inhibitor, in patients with solid tumours
Eur J Cancer 2018 Nov;103:17-23.PMID:30196106DOI:10.1016/j.ejca.2018.07.134.
Background: Dose-escalation of Epertinib (S-222611), a new potent oral EGFR/HER2 inhibitor, has established a recommended daily dose of 800 mg in patients with solid tumours. In this study, we have recruited a larger number of patients to assess further the safety, tolerability, pharmacokinetics (PKs) and antitumour activity. Patients and methods: Patients with solid tumours expressing EGFR or HER2 received a single dose of Epertinib at 800 mg on Day 1 to assess PK over 7 days, followed by continuous once-daily dosing from Day 8. Results: We treated 76 patients with breast (n = 27), upper gastrointestinal (GI; n = 30), head and neck (n = 12) or renal cancers (n = 7). Epertinib was well-tolerated with mostly grade I and II adverse events (AEs). The most frequent AE was diarrhoea, which was generally manageable with loperamide. The objective response rate (ORR) in patients with heavily pretreated breast and upper GI cancers was 16.0% (4 PRs) and 8.3% (1CR, 1PR), respectively. All six responding patients had HER2-positive tumours; the ORR for HER2-positive breast and upper GI cancer populations was 19.0% and 20.0%. Partial response in the brain disease of one breast cancer patient lasted 7.5 months. Conclusion: Once-daily dosing of Epertinib at 800 mg was well-tolerated and demonstrated promising antitumour activity in patients with heavily pretreated HER2-positive breast and upper GI cancer, including those with brain metastases. Eudract number: 2009-017817-31.
A phase I/II study of Epertinib plus trastuzumab with or without chemotherapy in patients with HER2-positive metastatic breast cancer
Breast Cancer Res 2019 Dec 31;22(1):1.PMID:31892325DOI:10.1186/s13058-019-1178-0.
Background: Epertinib (S-222611) is a potent reversible inhibitor of HER2, EGFR and HER4. This trial evaluated the safety, tolerability, pharmacokinetics and antitumour activity of daily oral Epertinib combined with trastuzumab (arm A), with trastuzumab plus vinorelbine (arm B) or with trastuzumab plus capecitabine (arm C), in patients with HER2-positive metastatic breast cancer (MBC). Methods: Eligible patients, with or without brain metastases, had received prior HER2-directed therapy. A dose-escalation phase determined the tolerability of each combination and established a dose for further study. Further, patients were recruited to expansion cohorts in each of the 3 arms to further explore efficacy and safety. Results: The recommended doses of Epertinib were 600 mg, 200 mg and 400 mg in arms A, B and C, respectively. The most frequent grade 3/4 adverse event (AE) was diarrhoea in all arms, which was manageable with medical intervention and dose modification. The objective response rate (complete response [CR] plus partial response [PR]) in heavily pre-treated HER2-positive MBC patients at the recommended doses of Epertinib combined with trastuzumab was 67% (N = 9), with trastuzumab plus vinorelbine was 0% (N = 5) and with trastuzumab plus capecitabine was 56% (N = 9). Notably, 4 of 6 patients previously treated with T-DM1 responded in the arm A expansion cohort (Epertinib plus trastuzumab). In the arm C expansion cohort (Epertinib plus trastuzumab plus capecitabine), 4 of 7 patients responded despite previous exposure to capecitabine. Measurable regression of brain metastases was observed in patients with CNS target lesions treated in both arms A and C. Conclusion: We observed safety, tolerability and encouraging antitumour activity of Epertinib combined with trastuzumab, or with trastuzumab plus capecitabine. This supports further evaluation of these combinations in patients with pre-treated HER2-positive MBC, with or without brain metastases. Trial registration: EudraCT Number: 2013-003894-87; registered 09-September-2013.