Selatinib
目录号 : GC68430Selatinib 是一种可逆且具有口服活性的双重 EGFR 和 ErbB2 抑制剂，IC50 分别为 13 nM 和 22.5 nM。Selatinib 具有抗癌作用。
Cas No.:1275595-86-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Selatinib is a reversible and orally active dual EGFR and ErbB2 inhibitor with IC50s of 13 nM and 22.5 nM, respectively. Selatinib has anticancer effects[1].
[1]. Meng-Na Wang, et al. First-in-human, phase I single-ascending-dose study of the safety, pharmacokinetics, and relative bioavailability of selatinib, a dual EGFR-ErbB2 inhibitor in healthy subjects. Invest New Drugs. 2020 Dec;38(6):1826-1835.
| Cas No. | 1275595-86-2 | SDF | Download SDF |
| 分子式 | C29H26ClFN4O3S | 分子量 | 565.06 |
| 溶解度 | DMSO : 100 mg/mL (176.97 mM; Need ultrasonic) | 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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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7697 mL | 8.8486 mL | 17.6972 mL |
| 5 mM | 0.3539 mL | 1.7697 mL | 3.5394 mL |
| 10 mM | 0.177 mL | 0.8849 mL | 1.7697 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
First-in-human, phase I single-ascending-dose study of the safety, pharmacokinetics, and relative bioavailability of Selatinib, a dual EGFR-ErbB2 inhibitor in healthy subjects
Invest New Drugs 2020 Dec;38(6):1826-1835.PMID:32535812DOI:10.1007/s10637-020-00959-6.
We assessed the pharmacokinetics and safety of a single oral administration of Selatinib to healthy Chinese subjects and evaluated the potential bioavailability advantage of Selatinib relative to lapatinib. Healthy subjects aged 18-40 years were enrolled in this two-part study: Part 1, a single ascending dose (50-500 mg), randomized, double-blind, placebo-control study with 64 subjects; and Part 2, an open-label, positive control, randomized, three-treatment, three-period, three-sequence crossover design study, with 6 subjects administered a single 500-mg dose of Selatinib tablets (A), Selatinib suspension (B), or lapatinib tablets C) per cycle. In part 1, Selatinib was well-tolerated up to the planned maximum dose of 500 mg; thus the maximum tolerated dose was not attained. Twenty-two adverse events were observed in 19 (36.5%) of the 52 subjects administered the test drug. The most common drug-related adverse event was diarrhea. The mean Selatinib peak plasma concentration was 69.4-494 ng/mL, which was achieved in a median peak time of 3.5-4.5 h, with a mean elimination half-life between 13.8 and 15.8 h. In Part 2, A and B showed similar bioavailability. Plasma exposure to the active drug (Selatinib plus the metabolite, lapatinib) after A intake was more than two-fold higher than that of the same dose of C. In the dose range of 50-500 mg, Selatinib was safe and well-tolerated by healthy Chinese subjects, and it conformed with linear pharmacokinetics. Active exposure to Selatinib was much greater than that to lapatinib, supporting its development as an adjuvant for anticancer treatment.
Discovery of a potent dual EGFR/HER-2 inhibitor L-2 (Selatinib) for the treatment of cancer
Eur J Med Chem 2013 Nov;69:833-41.PMID:24121234DOI:10.1016/j.ejmech.2013.09.032.
To develop potent dual EGFR/HER-2 inhibitors with improved druggability, a series of new lapatinib analogs were designed and synthesized. Compared with lapatinib, L-2, L-4 and M-6 were more active against BT-474 or NCI-N87 cells. In vivo efficacy studies indicated that L-2 significantly suppressed tumor growth in NCI-N87 (94.8% inhibition) or SK-OV-3 xenograft (85.7% inhibition) without causing significant loss of body weight. And the inhibition rates of lapatinib in the two xenograft models were 89.7% and 78.8%, respectively. Moreover, further studies revealed that the potent in vivo activities of L-2 may be mainly attributed to its superior aqueous solubility and oral bioavailability. In addition, a high-yielding one-pot procedure was developed for the synthesis of lapatinib and its analogs.
[Metabolic research of domestically developed small molecule tyrosine kinase inhibitors]
Yao Xue Xue Bao 2016 Feb;51(2):248-56.PMID:29856578doi
Drug metabolism research plays an essential role in drug discovery and development. Great efforts have been made domestically to be line with the international standardized research on drug metabolism. In this article, we will review new-generation of tyrosine kinase inhibitors(TKIs), these TKIs include icotinib, apatinib, famitinib, flumatinb, allitinib, fruquintinib, and Selatinib, among which icotinib and apatinib have been approved by China food and drug administration(CFDA) to reach the market, while others are in clinical trials. For these TKIs, the structural modified sites are active metabolic centers and CYP3A4 is identified as the primary metabolic enzyme. Considering the active intermediates, the crown ether ring of icotinib is oxidated to open to form an aldehyde; the indolylidene ring of famitinib is oxidated followed by rearrangement to form a quinone- imine; the α, β-unsaturated carbonyl group of allitinib is oxidated to form an epoxide, these intermediates are capable of covalently binding biomolecules and generating toxicity. In addition, human (14)C radioactive trials of most of these TKIs have not been conducted, and the data of drug-drug interactions in clinic are also absent, which indicate our deficiency compared to the international regular approaches in metabolic research.