Temozolomide (CCRG 81045)

製品コード:S1237 別名:NSC 362856,TMZ

For research use only.

Temozolomide (CCRG81045, NSC 362856, TMZ) is a monofunctional SN-1 alkylating agent that can modify nitrogen atoms in the DNA ring and the extracyclic oxygen group, chemically converted to MTIC and degrades to methyldiazonium cation, which transfers methyl groups to DNA at physiologic pH. A DNA damage inducer in L-1210 and L-1210/BCNU cells. Temozolomide induces apoptosis and exhibits antitumor activity.

Temozolomide (CCRG 81045)化学構造

CAS No. 85622-93-1

サイズ 価格(税別)
10mM (1mL in DMSO) JPY 13300
JPY 13600
JPY 30200
JPY 146400

代表番号: 03-5615-9297|電子メール:[email protected]
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文献中Selleckの製品使用例(150)

製品安全説明書

DNA/RNA Synthesis阻害剤の選択性比較

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生物活性

製品説明 Temozolomide (CCRG81045, NSC 362856, TMZ) is a monofunctional SN-1 alkylating agent that can modify nitrogen atoms in the DNA ring and the extracyclic oxygen group, chemically converted to MTIC and degrades to methyldiazonium cation, which transfers methyl groups to DNA at physiologic pH. A DNA damage inducer in L-1210 and L-1210/BCNU cells. Temozolomide induces apoptosis and exhibits antitumor activity.
特性 Methazolastone is a second-generation alkylating agent.
ターゲット
DNA replication [1]
(L-1210, L-1210/BCNU cells)
体外試験

Methazolastone causes formation of DNA alkali-labile sites which are present in similar amounts and repaired at a similar rate in L-1210 and L-1210/BCNU cell lines. In L-1210 but not in L-1210/BCNU methazolastone induces an arrest of cells in SL-G2-M phases.[1] Methazolastone sensitivity of both chemo-sensitive and resistant cells (D54-R and U87-R) is enhanced significantly under hyperoxia. Both Methazolastone and hyperoxia are associated with increased phosphorylation of ERK p44/42 MAPK (Erk1/2), but to a lesser extent in D54-R cells, suggesting that Erk1/2 activity may be involved in regulation of hyperoxia and Methazolastone-mediated cell death. Hyperoxia enhances Methazolastone toxicity in GBM cells by induction of apoptosis, possibly via MAPK-related pathways. [2] Methazolastone induces in monocytes the DNA damage response pathways ATM-Chk2 and ATR-Chk1 resulting in p53 activation. [3] Chronic Methazolastone exposure results in acquired Methazolastone-resistance and elevates miR-21 expression. [4] Methazolastone treatment triggers endoplasmic reticula (ER) stress with increased expression of GADD153 and GRP78 proteins, and deceases pro-caspase 12 protein. Methazolastone induces autophagy through mitochondrial damage- and ER stress-dependent mechanisms to protect glioma cells. [5]

細胞データ
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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アッセイ
Methods Test Index PMID
Western blot pERK / ERK / p-p38 / p38 ; DR5 / c-FLIP / Survivin / XIAP 24436439
Growth inhibition assay Cell viability 25751281
Immunofluorescence Phalloidin / Phospho-H2A.X ; cleaved caspase-3 27375225 25663820
体内試験 After a daily i.p. dose of 40 mg/kg for 5 consecutive days (days 1-5 after tumor transplant), methazolastone increases life-span by 86% in L-1210 and 22% in L-1210/BCNU. In L-1210/BCNU no effect is seen after 100 μM or 200 μM treatment; only 400 μM methazolastone produced an accumulation of cells in premitotic phase but much less than in L-1210. In L-1210/BCNU the maximum accumulation of cells in SL-G2-M is, after 48 hours-72 hours, approximately 30% as compared to 23% in untreated cells. Cells accumulates in SL-G2-M occurred too when L- 1210 leukemia-bearing mice are treated i.v. with methazola stone (40 mg/kg). No such effect is seen on L-1210/BCNU cells from mice given the same drug dose. [1]

お薦めの試験操作(参考用のみ)

細胞試験:

[1]

  • 細胞株:L-1210 and L-1210/BCNU cells
  • 濃度: 0 μM -100 μM
  • 反応時間:l hours
  • 実験の流れ:

    L-1210 and L-1210/BCNU cells are seeded at 0.2 × 104 cells/mL and incubated for 24 hours. The cultures are treated with Methazolastone for l hours at 37oC, then washed twice in PBS by centrifugation and resuspended in fresh medium. Controls and treated samples are diluted in fresh medium 1:4 at 48 hours and 1:2 at 96 hours. Using these dilutions cell concentrations throughout the experiments are between 3 × 105 and 8 × 105/mL. Control growth is logarithmic in this range.

動物試験:

[1]

  • 動物モデル:DBA/2 mice with L-1210 and L-1210/BCNU cells
  • 投薬量:40 mg/kg
  • 投与方法:Administered via i.v.

溶解度 (25°C)

体外

体内

左から(NMPから)右の順に溶剤を製品に加えます(文献ではなく、Selleckの実験によるデータ):
5% DMSO+30% PEG 300+ddH2O
混合させたのち直ちに使用することを推奨します。

2mg/mL

化学情報

分子量 194.15
化学式

C6H6N6O2

CAS No. 85622-93-1
Storage 3年 -20°C
2年 -80°C in solvent
Smiles CN1C(=O)N2C=NC(=C2N=N1)C(=O)N

投与溶液組成計算機(クリア溶液)

ステップ1:実験データを入力してください。(実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します)

mg/kg g μL

ステップ2:投与溶媒の組成を入力してください。(ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください)

% DMSO % % Tween 80 % ddH2O
%DMSO %

計算結果:

投与溶媒濃度: mg/ml;

DMSOストック溶液調製方法: mg 試薬を μL DMSOに溶解する(濃度 mg/mL, 注:濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法:Take μL DMSOストック溶液に μL PEG300,を加え、完全溶解後μL Tween 80,を加えて完全溶解させた後 μL ddH2O,を加え完全に溶解させます。

投与溶媒調製方法:μL DMSOストック溶液に μL Corn oil,を加え、完全溶解。

注意:1.ストック溶液に沈殿、混濁などがないことをご確認ください;
2.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

便利ツール

質量 濃度 体積 分子量

臨床試験

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT05128734 Not yet recruiting Drug: Temozolomide|Drug: Olaparib Breast Cancer Triple Negative AHS Cancer Control Alberta December 1 2022 Phase 2
NCT04200066 Not yet recruiting Drug: Temozolomide Tamoxifen Maprotiline Glioblastoma|Brain Tumor University of Rochester June 1 2022 Phase 1
NCT03796507 Withdrawn Drug: Temozolomide Glioma of Brain University of Rochester|National Institutes of Health (NIH) September 1 2021 Early Phase 1
NCT04901702 Recruiting Drug: Onivyde|Drug: Talazoparib|Drug: Temozolomide Recurrent Solid Tumor|Recurrent Ewing Sarcoma|Recurrent Hepatoblastoma|Recurrent Malignant Germ Cell Tumor|Recurrent Malignant Solid Neoplasm|Recurrent Neuroblastoma|Recurrent Osteosarcoma|Recurrent Peripheral Primitive Neuroectodermal Tumor|Recurrent Rhabdoid Tumor|Recurrent Rhabdomyosarcoma|Recurrent Soft Tissue Sarcoma|Recurrent Wilms Tumor|Refractory Ewing Sarcoma|Refractory Hepatoblastoma|Refractory Malignant Germ Cell Tumor|Refractory Malignant Solid Neoplasm|Refractory Neuroblastoma|Refractory Osteosarcoma|Refractory Peripheral Primitive Neuroectodermal Tumor|Refractory Rhabdoid Tumor|Refractory Rhabdomyosarcoma|Refractory Soft Tissue Sarcoma St. Jude Children''s Research Hospital|Pfizer|Ipsen June 9 2021 Phase 1|Phase 2

(data from https://clinicaltrials.gov, updated on 2022-08-01)

技術サポート

ストックの作り方、阻害剤の保管方法、細胞実験や動物実験の際に注意すべき点など、製品を取扱う時に問い合わせが多かった質問に対しては取扱説明書でお答えしています。

Handling Instructions

他に質問がある場合は、お気軽にお問い合わせください。

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