ZM 336372

製品コードS2720 バッチS272001

印刷

化学情報

Synonyms

Zinc00581684

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₂₃H₂₃N₃O₃

分子量

389.45

CAS No.

208260-29-1

Solubility (25°C)*

体外

DMSO

78 mg/mL (200.28 mM)

Ethanol

2 mg/mL (5.13 mM)

Water

Insoluble

体内（毎回新しく調製した物を用意してください）

Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	0.97mg/ml (2.49mM)	Taking the 1 mL working solution as an example, add 50 μL of 19.4 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	0.39mg/ml (1.00mM)	Taking the 1 mL working solution as an example, add 50 μL of 7.8 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	ZM 336372 (Zinc00581684) は、IC50が70 nMの強力かつ選択的なc-Raf阻害剤であり、B-RAFに対し10倍の選択性を示し、PKA/B/C、AMPK、p70S6などを阻害しません。
in vitro	ZM 336372 shows 10-fold selectivity over B-Raf. This compound weakly inhibits SAPK2a/p38α and SAPK2b/p38β with IC50 of 2 μM, and is selective over 17 other protein kinases including PKA, PKC, AMPK, p42 MAPK, MKK1, SAPK1/JNK, and CDK1 even at the concentration of up to 50 μM. It does not prevent constitutive as well as growth factor or phorbol ester induced activation of MKKl or p42 MAPK/ERK2. Moreover, this chemical dose not reverse the phenotype of Ras- or Raf-transformed cell lines. Its treatment induces >100 activation of c-Raf and the B-Raf isoform, but it does not trigger any activation of MKKI or p42 MAPK/ERKP or induce any increase in the GTP-loading of Ras, suggesting that a feedback control loop exists by which Raf isoforms suppress their own activation, such that inhibition is always counterbalanced by reactivation. This compound-induced activation of c-Raf is not prevented by inhibition of the MAPK cascade, protein kinase C or phosphatidylinositide 3-kinase. It (1 μM) abolishes the upregulation of eNOS after treatment with hydrogen peroxide. Its treatment in carcinoid tumor cells results in progressive phosphorylation of Raf-1, mitogen-activated protein kinase 1/2, and extracellular signal-regulated kinase 1/2, and causes a significant reduction of bioactive hormone levels as well as the transcription factor, human achaete-scute homologue-1. Furthermore, this chemical treatment leads to a marked suppression of cellular proliferation and induction of the cell cycle inhibitors p21 and p18. It inhibits the proliferation of pheochromocytoma cells, and suppresses NE vasoactive peptide production. Its treatment in HepG2 induces the suppression of proliferation in a dose-dependent manner, suppression of hormone secretion, and up-regulation of cell cycle inhibitors. It also induces apoptosis in pancreatic adenocarcinoma cell lines by inhibiting glycogen synthase kinase-3β through phosphorylation of GSK-3β at Ser 9.

製品説明

ZM 336372 (Zinc00581684) は、IC50が70 nMの強力かつ選択的なc-Raf阻害剤であり、B-RAFに対し10倍の選択性を示し、PKA/B/C、AMPK、p70S6などを阻害しません。

in vitro

ZM 336372 shows 10-fold selectivity over B-Raf. This compound weakly inhibits SAPK2a/p38α and SAPK2b/p38β with IC50 of 2 μM, and is selective over 17 other protein kinases including PKA, PKC, AMPK, p42 MAPK, MKK1, SAPK1/JNK, and CDK1 even at the concentration of up to 50 μM. It does not prevent constitutive as well as growth factor or phorbol ester induced activation of MKKl or p42 MAPK/ERK2. Moreover, this chemical dose not reverse the phenotype of Ras- or Raf-transformed cell lines. Its treatment induces >100 activation of c-Raf and the B-Raf isoform, but it does not trigger any activation of MKKI or p42 MAPK/ERKP or induce any increase in the GTP-loading of Ras, suggesting that a feedback control loop exists by which Raf isoforms suppress their own activation, such that inhibition is always counterbalanced by reactivation. This compound-induced activation of c-Raf is not prevented by inhibition of the MAPK cascade, protein kinase C or phosphatidylinositide 3-kinase. It (1 μM) abolishes the upregulation of eNOS after treatment with hydrogen peroxide. Its treatment in carcinoid tumor cells results in progressive phosphorylation of Raf-1, mitogen-activated protein kinase 1/2, and extracellular signal-regulated kinase 1/2, and causes a significant reduction of bioactive hormone levels as well as the transcription factor, human achaete-scute homologue-1. Furthermore, this chemical treatment leads to a marked suppression of cellular proliferation and induction of the cell cycle inhibitors p21 and p18. It inhibits the proliferation of pheochromocytoma cells, and suppresses NE vasoactive peptide production. Its treatment in HepG2 induces the suppression of proliferation in a dose-dependent manner, suppression of hormone secretion, and up-regulation of cell cycle inhibitors. It also induces apoptosis in pancreatic adenocarcinoma cell lines by inhibiting glycogen synthase kinase-3β through phosphorylation of GSK-3β at Ser 9.

プロトコル(参考用のみ)

キナーゼアッセイ	In vitro kinase assay
キナーゼアッセイ	c-Raf kinase activity is assayed directly in Sl9 cell lysates. Human c-Raf is activated in Sf9 cells by cotransfection from baculovirus vectors containing DNA encoding v-Ras and Lck in the absence of ZM 336372. The cell lysates are then assayed for c-Raf activity in the presence of increasing concentrations of this compound.
細胞アッセイ	細胞株	H727 and BON
	濃度	Dissolved in DMSO, final concentrations ~500 μM
	反応時間	48, and 72 hours
	実験の流れ	Cells are exposed to various concentrations of ZM 336372 for 48 and 72 hours. After incubation, the medium is removed and cells are trypsinized. Cells are incubated on ice, and 2.5 μg/mL propidium iodide is added 5 minutes before flow cytometry. Data is acquired using a FACSCalibur benchtop flow cytometer using CellQuest acquisition and analysis software. Cytotoxicity is done using Cell Titer Glo Assay. Cell proliferation is measured using MTT assay.

参考

https://pubmed.ncbi.nlm.nih.gov/10421767/
https://pubmed.ncbi.nlm.nih.gov/12569550/
https://pubmed.ncbi.nlm.nih.gov/15956248/

https://pubmed.ncbi.nlm.nih.gov/16603190/
https://pubmed.ncbi.nlm.nih.gov/18299943/
https://pubmed.ncbi.nlm.nih.gov/20031160/

+ 展开

カスタマーフィードバック

: Data from [Data independently produced by , , Pharmaceutical Biology, 2016, 54(4):732-739.]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Deconvoluting Mechanisms of Acquired Resistance to RAF Inhibitors in BRAFV600E-Mutant Human Glioma [ Clin Cancer Res, 2021, 10.1158/1078-0432.CCR-21-2660]	PubMed: 34433654
Low-Dose Sorafenib Acts as a Mitochondrial Uncoupler and Ameliorates Nonalcoholic Steatohepatitis. [ Cell Metab, 2020, 5;31(5):892-908 e11]	PubMed: 32375062
Mitochondrial metabolic reprograming via BRAF inhibition ameliorates senescence. [ Exp Gerontol, 2019, 126:110691]	PubMed: 31421186
Comparative analysis of the phototoxicity induced by BRAF inhibitors and alleviation through antioxidants. [ Photodermatol Photoimmunol Photomed, 2019, 10.1111/phpp.12520]	PubMed: 31618797
Status of KRAS in iPSCs Impacts upon Self-Renewal and Differentiation Propensity. [ Stem Cell Reports, 2018, 11(2):380-394]	PubMed: 29983389
Discovery of a Chemical Probe Bisamide (CCT251236): An Orally Bioavailable Efficacious Pirin Ligand from a Heat Shock Transcription Factor 1 (HSF1) Phenotypic Screen [ J Med Chem, 2017, 60(1):180-201]	PubMed: 28004573
Effect of earthworm active protein on fibroblast proliferation and its mechanism. [Song S, et al. Pharm Biol, 2016, 54(4):732-9]	PubMed: 26931349

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。