Mirdametinib

カタログ番号 T6189 CAS 391210-10-9

別名: PD325901, PD0325901

Mirdametinib (PD325901) is an MEK inhibitor (IC50=0.33 nM) with selective, non-ATP-competitive, and oral activity. Mirdametinib exhibits antitumor activity by inhibiting p-ERK1/2 expression and inducing apoptosis.

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Mirdametinib, CAS 391210-10-9

パッケージサイズ	在庫状況	単価(税別)
サンプルについてお問い合わせ
5 mg	在庫あり	￥ 11,000
10 mg	在庫あり	￥ 16,000
25 mg	在庫あり	￥ 30,000
50 mg	在庫あり	￥ 42,500
100 mg	在庫あり	￥ 66,000
200 mg	在庫あり	￥ 98,500
500 mg	在庫あり	￥ 160,000
1 g	在庫あり	￥ 217,000
1 mL * 10 mM (in DMSO)	在庫あり	￥ 11,500

バルクのお問い合わせ

バッチを選択

純度: 99.91%

COA DATASHEET SDS HNMR HPLC

純度: 99.5%

COA DATASHEET SDS LCMS HNMR

純度: 99.18%

COA DATASHEET SDS HNMR HPLC

COA DATASHEET SDS

バッチの詳細情報はお問い合わせください

生物学的特性に関する説明

化学的特性

保存条件 & 溶解度情報

説明	Mirdametinib (PD325901) is an MEK inhibitor (IC50=0.33 nM) with selective, non-ATP-competitive, and oral activity. Mirdametinib exhibits antitumor activity by inhibiting p-ERK1/2 expression and inducing apoptosis.
ターゲット＆IC50	MEK:0.33 nM (cell free)
In vitro	METHODS: Eleven human melanoma cell lines were treated with Mirdametinib (0.1-1000 nM) for 72 h, and cell counts were determined using the trypan blue exclusion test. RESULTS: Mirdametinib (IC50=20-50 nM) effectively inhibited the growth of human melanoma cell lines with BRAF mutations (M14/A375P/A375M/A375SM/ME10538/ME4686/JR8) or without BRAF mutations (ME4405/ME13923). ME8959 both have wild-type BRAF and are slightly more resistant to Mirdametinib-mediated growth inhibition (IC50≥100 nM). [1] METHODS: Papillary thyroid carcinoma (PTC) cell lines K2 and TPC-1 were treated with Mirdametinib (0.1-1000 nmol/L) for 1-96 h. Target protein expression levels were detected by Western Blot. RESULTS: Mirdametinib effectively inhibited the phosphorylation of ERK1/2 in various PTC cell lines. [2]
In vivo	METHODS: To assay antitumor activity in vivo, Mirdametinib (20-25 mg/kg, 80 mmol/L citric buffer (pH 7)) was administered by gavage to Athymic Ncr-nu/nu mice harboring PTC tumors K2 or TPC-1 five times per week for three weeks. RESULTS: Mirdametinib completely inhibited tumor growth in mice inoculated with PTC cells K2 harboring BRAF mutations and significantly reduced tumor growth in mice inoculated with PTC cells TPC-1 harboring RET/PTC1 rearrangements. [2] METHODS: To assay anti-tumor activity in vivo, Mirdametinib (1.6-25 mg/kg, 0.5% hydroxypropylmethylcellulose + 0.2% Tween 80 in water) was administered orally to mice bearing mouse colorectal cancer tumor CT26 once daily for fourteen days. RESULTS: Mirdametinib significantly inhibited pERK levels in tumors. [3]
キナーゼ試験	Incorporation of 32P into myelin basic protein (MBP) is assayed in the presence of a glutathione S-transferase fusion protein containing p44MAP kinase (GST-MAPK) and a glutathione S-transferase protein containing p45MEK (GST-MEK). The assay solution contained 20 mM HEPES, pH 7.4, 10 mM MgCl2, 1 mM MnCl2, 1 mM EGTA, 50 mM [γ-32P]ATP, 10 mg GST-MEK, 0.5 mg GST-MAPK and 40 mg MBP in a final volume of 100 mL. Reactions are stopped after 20 minutes by addition of trichloroacetic acid and filtered through a GF/C filter mat. 32P retained on the filter mat is determined using a 1205 Betaplate [1].
細胞研究	A cell death detection enzyme-linked immunosorbent assay was used per the manufacturer's instructions. Briefly, 4 × 10^4 cells were plated in 24-well plates in triplicate the day before treatment. PTC cells were treated with 0.1 μmol/L PD0325901 for 96 hours. Cells treated with 1 μmol/L staurosporine served as positive controls for apoptosis. At the end of treatment, cells were lysed using the lysis buffer provided in the kit for 30 minutes at room temperature and then centrifuged in 24-well plates. Lysates (20 μL of supernatant) were transferred to streptavidin-coated wells and incubated for 2 hours at room temperature with two antibodies (biotin-labeled anti-histone antibody and peroxidase-conjugated anti-DNA antibody). After the wells were washed three times, the samples were incubated with peroxidase substrate (ABTS) and the amount of colored product was determined spectrophotometrically at 405 nm. The background was measured at 490 nm [2].
動物実験	Athymic Ncr-nu/nu mice were obtained from the National Cancer Institute at ages 6 to 8 weeks and housed for at least 1 week after arrival. Mice (10–14 per group) were anesthetized s.c. with a cocktail (100 μL/10 g body weight of 10 mg/mL ketamine and 1 mg/mL xylazine). K2 and TPC-1 cells stably infected with a retrovirus expressing luciferase (5 × 105 cells in 5 μL RPMI1640 medium) were inoculated into the thyroid gland, and the mice were monitored weekly for tumor growth by Xenogen (IVIS 200 imaging system) using Living Image 3.0 software. One week after inoculation, PD0325901 was dissolved in 80 mmol/L citric buffer (pH 7) by sonication and given to mice daily by oral gavage (20–25 mg/kg) for 3 weeks (5 consecutive days/week). Mice were sacrificed only due to tumor burden or loss of 20% of body weight. Tumor sizes were measured with calipers and tumor volume (V) was calculated by the formula (V = length × width × depth). Control mice were given 80 mmol/L citric buffer (pH 7) alone. All in vivo experiments were done at least twice [2].

別名	PD325901, PD0325901
分子量	482.19
分子式	C16H14F3IN2O4
CAS No.	391210-10-9

保存条件

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度情報

5% DMSO+95% Saline: 0.61 mg/mL (1.25 mM, precipitation)

H2O: Insoluble

DMSO: 50 mg/mL (103.69 mM)

参考文献

1. Ciuffreda L, et al. Growth-inhibitory and antiangiogenic activity of the MEK inhibitor PD0325901 in malignant melanoma with or without BRAF mutations. Neoplasia. 2009 Aug;11(8):720-31. 2. Henderson YC, et al. MEK inhibitor PD0325901 significantly reduces the growth of papillary thyroid carcinoma cells in vitro and in vivo. Mol Cancer Ther. 2010 Jul;9(7):1968-76. 3. Barrett SD, et al. The discovery of the benzhydroxamate MEK inhibitors CI-1040 and PD 0325901. Bioorg Med Chem Lett. 2008 Dec 15;18(24):6501-4. 4. Lin T, et al. A chemical platform for improved induction of human iPSCs. Nat Methods. 2009 Nov;6(11):805-8. 5. Li Y, He Y, Peng J, et al. Mutant Kras co-opts a proto-oncogenic enhancer network in inflammation-induced metaplastic progenitor cells to initiate pancreatic cancer[J]. Nature Cancer. 2020: 1-17. 6. Chen F, Zhang M, Feng X, et al. Discovery of a Novel Long Noncoding RNA Lx8-SINE B2 as a Marker of Pluripotency[J]. Stem Cells International. 2021, 2021. 7. Guo Z, Kang S, Sun D, et al. MAPK-dependent hormonal signaling plasticity contributes to overcoming Bacillus thuringiensis toxin action in an insect host[J]. Nature Communications. 2020, 11(1): 1-14.

引用文献

1. Guo Z, Guo L, Qin J, et al. A single transcription factor facilitates an insect host combating Bacillus thuringiensis infection while maintaining fitness. Nature Communications. 2022, 13(1): 1-15. 2. Guo Z, Kang S, Sun D, et al. MAPK-dependent hormonal signaling plasticity contributes to overcoming Bacillus thuringiensis toxin action in an insect host. Nature Communications. 2020 Jun 12;11(1):3003. doi: 10.1038/s41467-020-16608-8. 3. Kuang, Junqi, et al. SS18 regulates pluripotent-somatic transition through phase separation.. Nature Communications. 2021 Jul 2;12(1):4090. doi: 10.1038/s41467-021-24373-5. 4. Wang W, Ren S, Lu Y, et al. Inhibition of Syk promotes chemical reprogramming of fibroblasts via metabolic rewiring and H2S production. The EMBO Journal. 2021 Jun 1;40(11):e106771. doi: 10.15252/embj.2020106771. Epub 2021 Apr 28. 5. Lin R, Zhai Z, Kuang J, et al. H3K27ac mediated SS18/BAFs relocation regulates JUN induced pluripotent-somatic transition. Cell & Bioscience. 2022, 12(1): 1-14 6. Guo Z, Kang S, Wu Q, et al. The regulation landscape of MAPK signaling cascade for thwarting Bacillus thuringiensis infection in an insect host. PLoS pathogens. 2021, 17(9): e1009917. 7. Chen F, Zhang M, Feng X, et al. Discovery of a Novel Long Noncoding RNA Lx8-SINE B2 as a Marker of Pluripotency. Stem Cells International. 2021 Feb 6;2021:6657597. doi: 10.1155/2021/6657597. eCollection 2021. 8. Yu Y, Li X, Jiao R, et al.H3K27me3-H3K4me1 transition at bivalent promoters instructs lineage specification in development.Cell & Bioscience.2023, 13(1): 1-20. 9. Yang Y, Xiao L, Xue Y, et al.ZBTB7A regulates primed‐to‐naïve transition of pluripotent stem cells via recognition of the PNT‐associated sequence by Zinc Fingers 1–2 and recognition of γ‐globin− 200 gene element by Zinc Fingers 1–4.The FEBS Journal.2023

投与量変換

You can also refer to dose conversion for different animals. 詳細

In vivo投与量計算 (透明溶液)

ステップ1: 以下の情報を入力してください

投与量

mg/kg

動物の平均体重

動物あたりの投与量

動物数

溶媒の組成を入力してください

% DMSO+

% +

% Tween 80+

% ddH₂O

%DMSO+

計算するリセット

計算結果:

作業濃度: mg/ml;

DMSO溶液の作成方法: mg あらかじめ溶解した薬剤 μL DMSO (マスター溶液の濃度 mg/mL)，濃度がそのバッチの薬剤のDMSO溶解度を超える場合は、まずご連絡ください。

生体内薬剤の調合法：取る μL DMSO マスター溶液、次に追加 μL PEG300，確実に混ぜてから加える μL Tween 80，確実に混ぜてから加える μL ddH₂O, 確実に混ぜる

お問合せ内容:

必ず順番通りに溶媒を加えてください。ボルテックスミキサーや超音波、湯煎することで溶解しやすくなります

計算器

モル濃度計算機

希釈計算機

再構成計算

分子量計算機

質量

濃度

体積

分子量

モル度計算機では以下の計算が可能です

既知の体積と濃度の溶液を調製するために必要な化合物の質量
質量が既知の化合物を目的の濃度まで溶解させるのに必要な溶液の量
特定の体積の中に既知の質量の化合物を入れて得られる溶液の濃度

参考例

モル濃度計算機を使用したモル濃度計算の例
化合物の分子量が197.13g/molである場合、10mlの水に10mMのストック溶液を作るのに必要な化合物の質量はどれくらいですか？
［分子量（MW）］の欄に［197.13］と入力してください
[濃度]ボックスに10と入力し、正しい単位（millimolar）を選択します
[容量]ボックスに10と入力し、正しい単位（milliliter）を選択します
計算を押します
答えの19.713mgが質量欄に表示されます

濃度 (開始)

体積 (開始)

濃度 (終了)

体積 (終了)

溶液を作るのに必要な希釈率の計算

溶液の調製に必要な希釈率の算出
希釈計算機は、既知の濃度の原液をどのように希釈するかを計算することができる便利なツールです。V1を計算するためにC1、C2＆V2を入力します。

参考例

Tocrisの希釈計算器を用いた希釈計算の一例
50μMの溶液を20ml作るためには、10mMの原液を何ml必要ですか？
C1V1=C2V2という式を用いて、C1=10mM、C2=50μM、V2=20ml、V1を未知数とします。
濃度（開始）ボックスに10を入力し正しい単位(millimolar)を選択してください
濃度（終了）ボックスに50を入力し正しい単位(millimolar)を選択してください
体積（終了）ボックスに20を入力し正しい単位(millimolar)を選択してください
計算を押します
100 microliter (0.1 ml) という答えが体積（開始）ボックスに表示されます。

分子式

分子量 g/mol

化合物の化学式を入力して、そのモル質量や元素組成を計算します

Tヒント：化学式は大文字と小文字を区別します。: C10H16N2O2 c10h16n2o2

化合物のモル質量（分子量）を計算する手順:
化学物質のモル質量を計算するには、その化学式を入力し、「計算」をクリックしてください。.
分子質量、分子量、モル質量、モル重量の定義:
分子質量（分子量）とは、物質の1分子の質量であり、統一された原子質量単位（u）で表されます。(1uは炭素12の1原子の質量の1/12に等しい）
モル質量（molar weight）とは、ある物質の1モルの質量のことで、単位はg/molです。

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技術サポート

Please see Inhibitor Handling Instructions for more frequently ask questions. Topics include: how to prepare stock solutions, how to store products, and cautions on cell-based assays & animal experiments, etc.

Keywords

Mirdametinib 391210-10-9 Apoptosis Autophagy MAPK MEK PD325901 PD 0325901 MAPKK Mitogen-activated protein kinase kinase PD-0325901 PD0325901 inhibit MAP2K PD-325901 Inhibitor PD 325901 inhibitor

本ウェブサイトに掲載されている製品は全て研究用試薬です。研究目的以外の用途にはご使用できません。

Mirdametinib

保存条件

溶解度情報

参考文献

引用文献

関連化合物ライブラリー

関連製品

投与量変換

In vivo投与量計算 (透明溶液)

計算器

モル度計算機では以下の計算が可能です

溶液を作るのに必要な希釈率の計算

バイアルを再構成するのに必要な溶媒の量を計算する.

化合物の化学式を入力して、そのモル質量や元素組成を計算します

技術サポート

Keywords