セルメチニブ
概要
説明
セルメチニブは、コセルゴという商品名で販売されている薬剤であり、主に2歳以上の小児における神経線維腫症1型（NF-1）の治療に使用されます。 NF-1は、神経に腫瘍を生じさせる神経系の遺伝子疾患です . セルメチニブは、Raf-MEK-ERKシグナル伝達経路の重要な構成要素である、ミトゲン活性化プロテインキナーゼ1および2（MEK1/2）の選択的阻害剤です .
科学的研究の応用
Selumetinib has a wide range of scientific research applications, including:
Chemistry: Used as a tool to study the Raf-MEK-ERK signaling pathway and its role in various cellular processes.
Biology: Investigated for its effects on cell growth, differentiation, and apoptosis in various cell lines.
Industry: Utilized in the development of targeted therapies for cancer treatment.
作用機序
セルメチニブは、Raf-MEK-ERKシグナル伝達経路の重要な構成要素であるMEK1およびMEK2を選択的に阻害することで、その効果を発揮します . これらのタンパク質を阻害することで、セルメチニブは細胞の増殖と生存を促進する下流のシグナル伝達をブロックします。 この阻害は、G1-S期の細胞周期の停止につながり、がん細胞のアポトーシスを誘導します .
類似化合物の比較
セルメチニブは、トラメチニブやコビメチニブなどの他のMEK阻害剤と比較されます。 3つの化合物はすべてMEK1/2タンパク質を標的にしていますが、セルメチニブは化学構造と薬物動態が独特です . たとえば、トラメチニブとコビメチニブは異なる分子構造を持っており、臨床設定では有効性と安全性プロファイルが異なる場合があります .
類似化合物
- トラメチニブ
- コビメチニブ
- ビニメチニブ
セルメチニブの独自性は、MEK1/2に対する特異的な結合親和性と選択性にあるため、神経線維腫症1型やその他の腫瘍の治療における有効性に貢献しています .
準備方法
セルメチニブは、多段階の化学プロセスを経て合成されます最終段階は、カルボキサミド基の形成が含まれます . 産業生産方法では、通常、反応条件を最適化して、収率と純度を最大化し、不純物の生成を最小限に抑えます。
化学反応の分析
セルメチニブは、以下を含むいくつかの種類の化学反応を起こします。
これらの反応で使用される一般的な試薬や条件には、酸化剤、光への曝露、酸性または塩基性溶液などがあります。これらの反応から生成される主要な生成物は、アミド誘導体とエステル誘導体です。
科学研究への応用
セルメチニブは、以下を含む幅広い科学研究用途があります。
類似化合物との比較
Selumetinib is compared with other MEK inhibitors such as trametinib and cobimetinib. While all three compounds target the MEK1/2 proteins, selumetinib is unique in its chemical structure and pharmacokinetic properties . For example, trametinib and cobimetinib have different molecular structures and may exhibit different efficacy and safety profiles in clinical settings .
Similar Compounds
- Trametinib
- Cobimetinib
- Binimetinib
Selumetinib’s uniqueness lies in its specific binding affinity and selectivity for MEK1/2, which contributes to its effectiveness in treating neurofibromatosis type 1 and other tumors .
特性
IUPAC Name |
6-(4-bromo-2-chloroanilino)-7-fluoro-N-(2-hydroxyethoxy)-3-methylbenzimidazole-5-carboxamide |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C17H15BrClFN4O3/c1-24-8-21-16-13(24)7-10(17(26)23-27-5-4-25)15(14(16)20)22-12-3-2-9(18)6-11(12)19/h2-3,6-8,22,25H,4-5H2,1H3,(H,23,26) |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
CYOHGALHFOKKQC-UHFFFAOYSA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
CN1C=NC2=C1C=C(C(=C2F)NC3=C(C=C(C=C3)Br)Cl)C(=O)NOCCO |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C17H15BrClFN4O3 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
DSSTOX Substance ID |
DTXSID3048944 |
Source
|
| Record name | Selumetinib | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID3048944 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
457.7 g/mol |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Mechanism of Action |
The Ras-Raf-MEK-ERK signaling cascade is known to be activated in several types of cancer, and regulates the transcription of proteins involved in apoptosis. In addition, studies have shown that mutations of the Raf component of the pathway can contribute to chemotherapy drug resistance. Ras as well as several kinases and phosphatases are responsible for regulating the Raf-MEK-ERK pathway. Often in cancers, Ras (a G-protein coupled receptor) is deregulated, allowing downstream signalling to proceed unchecked. Through several complex steps, Raf phosphorylates and activates MEK, which then phosphorylates and activates ERK. ERK is then able to exert its effects on several downstream targets. As such, therapies inhibiting upstream components of this pathway have become attractive targets for cancer treatment. Selumetinib exerts its effects by selectively inhibiting MEK1 and MEK2 which can effectively blunt the pleiotropic effects of the Ras-Raf-MEK-ERK cascade. By inhibiting this oncogenic pathway, selumetinib reduces cell proliferation, and promotes pro-apoptotic signal transduction. |
Source
|
| Record name | Selumetinib | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB11689 | |
| Description | The DrugBank database is a unique bioinformatics and cheminformatics resource that combines detailed drug (i.e. chemical, pharmacological and pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information. | |
| Explanation | Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode) | |
CAS No. |
606143-52-6 |
Source
|
| Record name | Selumetinib | |
| Source | CAS Common Chemistry | |
| URL | https://commonchemistry.cas.org/detail?cas_rn=606143-52-6 | |
| Description | CAS Common Chemistry is an open community resource for accessing chemical information. Nearly 500,000 chemical substances from CAS REGISTRY cover areas of community interest, including common and frequently regulated chemicals, and those relevant to high school and undergraduate chemistry classes. This chemical information, curated by our expert scientists, is provided in alignment with our mission as a division of the American Chemical Society. | |
| Explanation | The data from CAS Common Chemistry is provided under a CC-BY-NC 4.0 license, unless otherwise stated. | |
| Record name | Selumetinib [USAN:INN] | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0606143526 | |
| Description | ChemIDplus is a free, web search system that provides access to the structure and nomenclature authority files used for the identification of chemical substances cited in National Library of Medicine (NLM) databases, including the TOXNET system. | |
| Record name | Selumetinib | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB11689 | |
| Description | The DrugBank database is a unique bioinformatics and cheminformatics resource that combines detailed drug (i.e. chemical, pharmacological and pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information. | |
| Explanation | Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode) | |
| Record name | Selumetinib | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID3048944 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
| Record name | 5-[(4-bromo-2-chlorophenyl)amino]-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-1,3-benzodiazole-6-carboxamide | |
| Source | European Chemicals Agency (ECHA) | |
| URL | https://echa.europa.eu/information-on-chemicals | |
| Description | The European Chemicals Agency (ECHA) is an agency of the European Union which is the driving force among regulatory authorities in implementing the EU's groundbreaking chemicals legislation for the benefit of human health and the environment as well as for innovation and competitiveness. | |
| Explanation | Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page. | |
| Record name | SELUMETINIB | |
| Source | FDA Global Substance Registration System (GSRS) | |
| URL | https://gsrs.ncats.nih.gov/ginas/app/beta/substances/6UH91I579U | |
| Description | The FDA Global Substance Registration System (GSRS) enables the efficient and accurate exchange of information on what substances are in regulated products. Instead of relying on names, which vary across regulatory domains, countries, and regions, the GSRS knowledge base makes it possible for substances to be defined by standardized, scientific descriptions. | |
| Explanation | Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required. | |
Synthesis routes and methods
Procedure details
Retrosynthesis Analysis
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Strategy Settings
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| Template Set | Pistachio/Bkms_metabolic/Pistachio_ringbreaker/Reaxys/Reaxys_biocatalysis |
| Top-N result to add to graph | 6 |
Feasible Synthetic Routes
試験管内研究製品の免責事項と情報
BenchChemで提示されるすべての記事および製品情報は、情報提供を目的としています。BenchChemで購入可能な製品は、生体外研究のために特別に設計されています。生体外研究は、ラテン語の "in glass" に由来し、生物体の外で行われる実験を指します。これらの製品は医薬品または薬として分類されておらず、FDAから任何の医療状態、病気、または疾患の予防、治療、または治癒のために承認されていません。これらの製品を人間または動物に体内に導入する形態は、法律により厳格に禁止されています。これらのガイドラインに従うことは、研究と実験において法的および倫理的な基準の遵守を確実にするために重要です。
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