SCH772984 |
カタログ番号GC16001
One-Click Copy Product Info
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SCH772984はERK1とERK2の新型で、強力で、ATP競合的な阻害剤で、IC50値はそれぞれ4nMと1nMである。
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 942183-80-4
Sample solution is provided at 25 µL, 10mM.
SCH772984はERK1とERK2の新型で、強力で、ATP競合的な阻害剤で、IC50値はそれぞれ4nMと1nMである[1]。SCH772984はERK基質p90リボソームS6キナーゼ（T359/S363リン酸-RSK）のリン酸化を阻害し、ERK自身の活性ループにおける残基のリン酸化をも阻害する[2]。SCH772984はネイティブMAPK阻害とMAPK阻害に抵抗する細胞のBRAFまたはRAS変異に対して、抗腫瘍活性を持つ[3]。
試験管内では、SCH772984（0-10μM）で72-120時間処理され14個のNRAS変異黒色腫細胞株のうち11個はSCH772984に感受性が高く、IC50<1μMであった[4]。SCH772984 (0-10μM)でヒト非小細胞肺癌細胞株（NCI-H727細胞）を6時間と24時間処理した結果、親H727細胞と二つのMEKとERK耐性サブラインで、6時間と24時間後にERKとその他のタンパク質のリン酸化を下方制御した[5]。
生体内では、SCH772984 (10mg/kg) で敗血のマウスに腹腔内注射した結果、マウスの生存率を増やし、Ccl2/Mcp1の血漿レベルを減らし、腎臓と肝臓における免疫反応と止血と関連する分子プロセスを阻害し、肺と肝臓における細胞外マトリックス（ECM）の組織化とレチノイン酸（RA）シグナル伝達経路を活性化した[6]。SCH772984 (0.1, 1.0, 10μg)を脛骨癌疼痛モデルのラットに鞘内注射し、用量依存的に鎮痛作用を生産し、脊髄後角のFosタンパク質の発見を著しく減らした[7]。
References:
[1] Morris E J, Jha S, Restaino C R, et al. Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors[J]. Cancer discovery, 2013, 3(7): 742-750.
[2] Li H, Wang C, Gong Z, et al. Transient Receptor Potential Ankyrin 1-dependent Activation of Extracellular Signal-regulated Kinase 2 in the Cerebral Cortices Contributes to Cortical Spreading Depolarization[J]. Neuroscience, 2024, 543: 90-100.
[3] Miao L, Tian H. Development of ERK1/2 inhibitors as a therapeutic strategy for tumour with MAPK upstream target mutations[J]. Journal of drug targeting, 2020, 28(2): 154-165.
[4] Wong D J L, Robert L, Atefi M S, et al. Antitumor activity of the ERK inhibitor SCH722984 against BRAF mutant, NRAS mutant and wild-type melanoma[J]. Molecular cancer, 2014, 13: 1-15.
[5] Moschos S J, Sullivan R J, Hwu W J, et al. Development of MK-8353, an orally administered ERK1/2 inhibitor, in patients with advanced solid tumors[J]. JCI insight, 2018, 3(4).
[6] Kopczynski M, Rumienczyk I, Kulecka M, et al. Selective extracellular signal-regulated kinase 1/2 (erk1/2) inhibition by the sch772984 compound attenuates in vitro and in vivo inflammatory responses and prolongs survival in murine sepsis models[J]. International Journal of Molecular Sciences, 2021, 22(19): 10204.
[7] Bian J, Zhu S, Ma W, et al. Analgesic effect and possible mechanism of SCH772984 intrathecal injection on rats with bone cancer pain[J]. Saudi Pharmaceutical Journal, 2016, 24(3): 354-362.
| 細胞実験[1]: | |
細胞株 | 14個のNRAS変異黒色腫細胞株 |
準備方法 | 全ての条件下で、全ての細胞株を、SCH772984、ベムラフェニブ、トラメチニブの単独または併用と一定量のDMSOで2回処理した。72-120時間の培養後に、細胞生存率を測定した。各実験を少なくとも3回独立で繰り返した。 |
反応条件 | 0-10μM；72-120時間 |
アプリケーション | 全てのNRAS変異細胞株はベムラフェニブに抵抗し、14の11個はSCH772984に敏感的であった(IC50<1μM)。 |
| 動物実験 [2]: | |
動物モデル | C57BL/6Wマウス |
準備方法 | C57BL/6Wマウスをそれぞれ、リポ多糖（LPS）（20mg/kg）または盲腸結紮穿刺（CLP）で、敗血症性ショックを誘発した。LPSグループでは、マウスに投与の2時間後に、10mg/kgのSCH772984または組み合わせ（3%のDMSO+10%のポリエチレングリコール）を腹腔内投与し、その後6時間ごとにSCH772984を注射した。CLP実験グループでは、CLP処置の2時間後に、マウスに10mg/kgのSCH772984または製剤を腹腔内注射した。マウスにそれぞれ6時間と12時間後の時点で、単回と二回用量のSCH772984を投与した。イソフルランで麻酔を誘発し、心臓穿刺で血液を採取した。胸腔を開け、心臓と肺を速やかにクライオバイアルへ採取し、液体窒素で快速冷凍した。その後、腎臓と肝臓を速やかに同じ方法で採取した。 |
投与形態 | 10mg/kg、単回と二回用量、6時間と12時間の時点；腹腔内投与 |
アプリケーション | SCH772984の処理で、LPS誘発性致死性内毒素血症と盲腸結紮穿刺(CLP)マウス敗血症モデルにおける生存率を向上させた。Ccl2/Mcp1 の血漿レベルを減らした。 |
References: | |
| Cas No. | 942183-80-4 | SDF | |
| Chemical Name | (3R)-1-[2-oxo-2-[4-(4-pyrimidin-2-ylphenyl)piperazin-1-yl]ethyl]-N-(3-pyridin-4-yl-1H-indazol-5-yl)pyrrolidine-3-carboxamide | ||
| Canonical SMILES | C1CN(CC1C(=O)NC2=CC3=C(C=C2)NN=C3C4=CC=NC=C4)CC(=O)N5CCN(CC5)C6=CC=C(C=C6)C7=NC=CC=N7 | ||
| Formula | C33H33N9O2 | M.Wt | 587.67 |
| 溶解度 | ≥ 14.7 mg/mL in DMSO with gentle warming | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7016 mL | 8.5082 mL | 17.0164 mL |
| 5 mM | 340.3 μL | 1.7016 mL | 3.4033 mL |
| 10 mM | 170.2 μL | 850.8 μL | 1.7016 mL |
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.50% Appearance: A solid
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- SDS (Safety Data Sheet)
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