SCH772984

カタログ番号 T6066 CAS 942183-80-4

SCH 772984 is a potent inhibitor of ERK1/ERK2 (IC50: 4/1 nM) and has only weak inhibitory for other 300 tested kinases.

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SCH772984, CAS 942183-80-4

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
1 mg	在庫あり	￥ 11,000
2 mg	在庫あり	￥ 16,000
5 mg	在庫あり	￥ 23,000
10 mg	在庫あり	￥ 35,000
25 mg	在庫あり	￥ 70,500
50 mg	在庫あり	￥ 105,500
100 mg	在庫あり	￥ 155,500
200 mg	在庫あり	￥ 221,000
500 mg	在庫あり	￥ 328,500
1 mL * 10 mM (in DMSO)	在庫あり	￥ 30,500

バルクのお問い合わせ

バッチを選択

純度: 98.75%

COA DATASHEET SDS HPLC

純度: 98.45%

COA DATASHEET SDS HNMR HPLC

純度: 98.01%

COA DATASHEET SDS HPLC LCMS HNMR

純度: 98%

COA DATASHEET SDS HNMR

純度: 97.65%

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	SCH 772984 is a potent inhibitor of ERK1/ERK2 (IC50: 4/1 nM) and has only weak inhibitory for other 300 tested kinases.
ターゲット＆IC50	ERK2:1 nM (cell free), ERK1:4 nM (cell free)
In vitro	SCH772984 potently inhibited ERK1 and ERK2 activity (IC50s: 4/1 nmol/L). SCH772984 is highly selective, with only seven kinases of 300 tested showing more than 50% inhibition at a concentration of 1 μmol/L. Treatment of the BRAFV600E-mutant human melanoma cell line LOXIMV1 (LOX) with SCH772984 resulted in a dose-dependent inhibition of phosphorylation of the ERK substrate p90 ribosomal S6 kinase. SCH772984 also inhibited phosphorylation of residues in the activation loop of ERK itself [1]. In a panel of 121 human tumor cell lines, SCH772984 showed EC50 values less than 500 nmol/L in approximately 88% and 49% of BRAF-mutant or RAS-mutant tumor lines, respectively [2].
In vivo	Treatment of BRAF-mutant LOX melanoma xenografts with SCH772984 (50 mg/kg twice daily) led to 98% tumor regression. Dose-dependent antitumor activity was also observed in the KRAS-mutant pancreatic MiaPaCa model, with 36% regression at 50 mg/kg twice daily [1].
キナーゼ試験	SCH772984 was tested in 8-point dilution curves in duplicate against purified ERK1 or ERK2. The enzyme was added to the reaction plate and incubated with the compound before adding a solution of substrate peptide and ATP. Fourteen microliters of diluted enzyme (0.3 ng active ERK2 per reaction) was added to each well of a 384-well plate. The plates were gently shaken to mix the reagents and incubated for 45 minutes at room temperature. The reaction was stopped with 60 μL of IMAP Binding Solution (1:2,200 dilutions of IMAP beads in 1× binding buffer). The plates were incubated at room temperature for an additional 0.5 hours to allow complete binding of phosphopeptides to the IMAP beads. Plates were read on the LJL Analyst [1].
細胞研究	For resistant cell line creation, cells were grown in Dulbecco's modified Eagle medium with 10% heat-inactivated FBS media and increasing concentrations of inhibitor (PLX4032, 0.1–10 μmol/L; GSK1120212, 0.01–1 μmol/L) over approximately 4 to 8 months until resistant cells acquired growth properties similar to na?ve parental cells (at their top drug concentrations). For combination resistance, cells were incubated as above but with alternative dose escalation until a top concentration was acquired (PLX4032 10 μmol/L and GSK1120212 1 μmol/L). Stocks and dilutions of PLX4032, GSK1120212, and SCH772984 were made in DMSO solvent. Cell proliferation experiments were carried out in a 96-well format (six replicates), and cells were plated at a density of 4,000 cells per well. At 24 hours after cell seeding, cells were treated with DMSO or a 9-point IC50 dilution (0.001–10 μmol/L) at a final concentration of 1% DMSO for all concentrations. Viability was assayed 5 days after dosing using the ViaLight luminescence kit following the manufacturer's recommendations (n = 6, mean ± SE). For the cell line panel viability assay, cells were treated with SCH772984 for 4 days and assayed by the CellTiterGlo luminescent cell viability assay. For IncuCyte analysis, cells were plated as above in 96-well plates, and image-based cell confluence data were collected every 2 hours during live growth. For engineered resistant lines, cells were infected with lentivirus produced from lentiORF constructs expressing either RFP, KRASG13D, BRAFV600E, truncated BRAFV600E lacking exons 2–8 (Δ2-8), MEK1P124L, MEK1F129L, or constitutively active MEK1DD (S218D+S222D). Cells were selected in blasticidin (20 μg/mL) and used for ViaLight assays as described above [1].
動物実験	Nude mice were injected subcutaneously with specific cell lines, grown to approximately 100 mm^3, randomized to treatment groups (10 mice/group), and treated intraperitoneally with either SCH772984 or vehicle according to the dosing schedule indicated in the figure legends. Tumor length (L), width (W), and height (H) were measured during and after the treatment periods by a caliper twice weekly on each mouse and then used to calculate tumor volume using the formula (L × W × H)/2. Animal body weights were measured on the same days twice weekly. Data were expressed as mean ± SEM. Upon completion of the experiment, vehicle- and SCH772984-treated tumor biopsies were processed for Western blot analysis [1].

分子量	587.67
分子式	C33H33N9O2
CAS No.	942183-80-4

保存条件

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

溶解度情報

H2O: < 1 mg/mL (insoluble or slightly soluble)

Ethanol: < 1 mg/mL (insoluble or slightly soluble)

DMSO: 51 mg/mL(86.8 mM)

参考文献

1. Morris EJ, et al. Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors. Cancer Discov. 2013 Jul;3(7):742-50. 2. Chaikuad A, et al. A unique inhibitor binding site in ERK1/2 is associated with slow binding kinetics. Nat Chem Biol. 2014 Oct;10(10):853-60. 3. Jiang S, Wang Z, Zhu T, et al. The Downregulation of EIF3a Contributes to Vemurafenib Resistance in Melanoma By Activating ERK Via PPP2R1B[J]. 2021 4. Lang J Y, Wang X, Xie Q, et al. Targeting KRAS-mutant stomach/colorectal tumours by disrupting the ERK2-p53 complex[J]. bioRxiv. 2020 5. Chang G, Xiao W, Xu Z, et al. Pterostilbene Induces Cell Apoptosis and Cell Cycle Arrest in T-Cell Leukemia/Lymphoma by Suppressing the ERK1/2 Pathway[J]. BioMed Research International. 2017;2017:9872073 6. Zhang B, Zhao J, Wang Z, et al. DL0410 attenuates oxidative stress and neuroinflammation via BDNF/TrkB/ERK/CREB and Nrf2/HO-1 activation[J]. International Immunopharmacology. 2020, 86: 106729. 7. Bin Y F, Ma N, Lu Y X, et al. Erythromycin reverses cigarette smoke extract-induced corticosteroid insensitivity by inhibition of the JNK/c-Jun pathway[J]. Free Radical Biology and Medicine. 2020, 152: 494-503. 8. Xie D, Ge X, Ma Y, et al. Clemastine improves hypomyelination in rats with hypoxic–ischemic brain injury by reducing microglia-derived IL-1β via P38 signaling pathway[J]. Journal of neuroinflammation. 2020, 17(1): 1-17. 9. Zhao Z, Xue F, Gu Y, et al. Crosstalk between the muscular estrogen receptor α and BDNF/TrkB signaling alleviates metabolic syndrome via 7, 8-dihydroxyflavone in female mice[J]. Molecular Metabolism. 2020: 101149. 10. Caiola E, Iezzi A, Tomanelli M, et al. LKB1 deficiency renders non-small-cell lung cancer cells sensitive to ERK inhibitors.: ERK inhibitors in LKB1 mutated NSCLC[J]. Journal of Thoracic Oncology. 2019.

引用文献

1. Wang X, Xie Q, Ji Y, et al.Targeting KRAS-mutant stomach/colorectal tumors by disrupting the ERK2-p53 complex.Cell Reports.2023, 42(1): 111972. 2. Lai J, Li Y, Ran M, et al.Xanthotoxin, a novel inducer of platelet formation, promotes thrombocytopoiesis via IL-1R1 and MEK/ERK signaling.Biomedicine & Pharmacotherapy.2023, 163: 114811. 3. Li M, Wang Z, Fu S, et al.Taurine reduction of injury from neutrophil infiltration ameliorates Streptococcus uberis-induced mastitis.International Immunopharmacology.2023, 124: 111028. 4. Jiang S, Wang Z, Zhu T, et al. The Downregulation of EIF3a Contributes to Vemurafenib Resistance in Melanoma By Activating ERK Via PPP2R1B. Frontiers in Pharmacology. 2021: 2242. 5. Zhang B, Zhao J, Wang Z, et al. DL0410 attenuates oxidative stress and neuroinflammation via BDNF/TrkB/ERK/CREB and Nrf2/HO-1 activation. International Immunopharmacology. 2020, 86: 106729. 6. Zhao Z, Xue F, Gu Y, et al. Crosstalk between the muscular estrogen receptor α and BDNF/TrkB signaling alleviates metabolic syndrome via 7, 8-dihydroxyflavone in female mice. Molecular Metabolism. 2020: 101149. 7. Caiola E, Iezzi A, Tomanelli M, et al. LKB1 Deficiency Renders NSCLC Cells Sensitive to ERK Inhibitors. Journal of Thoracic Oncology. 2020, 15(3): 360-370 8. Caiola E, Iezzi A, Tomanelli M, et al. LKB1 deficiency renders non-small-cell lung cancer cells sensitive to ERK inhibitors.: ERK inhibitors in LKB1 mutated NSCLC. Journal of Thoracic Oncology. 2019 9. Chang Y W, Wang C C, Yin C F, et al. Quantitative phosphoproteomics reveals ectopic ATP synthase on mesenchymal stem cells to promote tumor progression via ERK/c-Fos pathway activation. Molecular & Cellular Proteomics. 2022, 21(6) 10. Yang J, Wang X, Fan Y, et al. Tropoelastin improves adhesion and migration of intra-articular injected infrapatellar fat pad MSCs and reduces osteoarthritis progression. Bioactive Materials. 2021

11. Zeng F, Li Y, Deng Z, et al. SARS‐CoV‐2 Spike Spurs Intestinal Inflammation via VEGF Production in Enterocytes. EMBO Molecular Medicine. 2022 May 9;14(5):e14844. doi: 10.15252/emmm.202114844. Epub 2022 Apr 19. 12. Xie D, Ge X, Ma Y, et al. Clemastine improves hypomyelination in rats with hypoxic–ischemic brain injury by reducing microglia-derived IL-1β via P38 signaling pathway. Journal of neuroinflammation. 2020, 17(1): 1-17. 13. Bin Y F, Ma N, Lu Y X, et al. Erythromycin reverses cigarette smoke extract-induced corticosteroid insensitivity by inhibition of the JNK/c-Jun pathway. Free Radical Biology and Medicine. 2020, 152: 494-503 14. Chang G, Xiao W, Xu Z, et al. Pterostilbene Induces Cell Apoptosis and Cell Cycle Arrest in T-Cell Leukemia/Lymphoma by Suppressing the ERK1/2 Pathway. BioMed Research International. 2017;2017:9872073 15. Zhu F D, Wang B D, Qin D L, et al.Carpesii fructus extract exhibits neuroprotective effects in cellular and Caenorhabditis elegans models of Parkinson's disease.CNS Neuroscience & Therapeutics.2023

もっと見る隠し

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

SCH772984 942183-80-4 MAPK ERK MEK Extracellular signal regulated kinases Inhibitor inhibit SCH 772984 SCH-772984 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。

SCH772984

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