TMZ(Temozolomide)

製品コードS1237 バッチS123712

印刷

化学情報

Chemical Structure Synonyms NSC 362856,CCRG 81045,Methazolastone Storage
(From the date of receipt)		 3 years-20°C （in the dark）powder
化学式

C6H6N6O2
分子量 194.15 CAS No. 85622-93-1
Solubility (25°C)* 体外 DMSO (warmed with 50ºC water bath) 39 mg/mL (200.87 mM)
Water (warmed with 50ºC water bath) 7 mg/mL (36.05 mM)
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
5%DMSO 30%PEG300 65%ddH2O
2.0mg/ml Taking the 1 mL working solution as an example, add 50 μL of 40 mg/ml clarified DMSO stock solution to 300 μL of PEG 300, mix evenly to clarify it; then continue to add 650 μL of ddH2O to adjust the volume to 1 mL. 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 テモゾロミド (Temozolomide (NSC 362856,TMZ,CCRG 81045,Methazolastone)) はDNA 環上の窒素原子と環外酸素を修飾することが可能な単官能性 SN1 アルキル化剤であり、中間体である MTIC を経て、活性代謝産物であるメチルジアゾニウムカチオン (methyl diazoniumcation) に分解されると、生理学的 pH において DNA にメチル基を転移します。テモゾロミドはアポトーシス (apoptosis) を誘発し、抗がん活性を呈します。L-1210 細胞および L-1210/BCNU 細胞における DNA 損傷誘導剤です。
in vitro

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]
in vivo

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]
特徴 Methazolastone is a second-generation alkylating agent.

プロトコル(参考用のみ)

細胞アッセイ 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.
動物実験 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.

カスタマーフィードバック

Data from [Data independently produced by Clin Cancer Res, 2014, 20(6), 1555-65]

Data from [Data independently produced by , , Clin Cancer Res, 2017, 23(20):6239-6253]

Data from [Data independently produced by , , Clin Cancer Res, 2017, 23(2):523-535]

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：

Daurisoline suppress glioma progression by inhibiting autophagy through PI3K/AKT/mTOR pathway and increases TMZ sensitivity [ Biochem Pharmacol, 2024, 223:116113] PubMed: 38460907
Establishment of tumor microenvironment-preserving organoid model from patients with intracranial meningioma [ Cancer Cell Int, 2024, 24(1):36] PubMed: 38238738
Borneol promotes autophagic degradation of HIF-1α and enhances chemotherapy sensitivity in malignant glioma [ PeerJ, 2024, 12:e16691] PubMed: 38188151
Boswellic acid formulations are not suitable for treatment of pediatric high-grade glioma due to tumor promoting potential [ J Tradit Complement Med, 2024, 14(1):101-108] PubMed: 38223806
A CANCER PERSISTENT DNA REPAIR CIRCUIT DRIVEN BY MDM2, MDM4 (MDMX), AND MUTANT P53 FOR RECRUITMENT OF MDC1 AND 53BP1 TO [ bioRxiv, 2024, 2024.01.20.576487.] PubMed: 38328189
Hypoxia promotes temozolomide resistance in glioblastoma cells via ROS-mediated up-regulation of TRPM2 [ Research Square, 2024, 10.21203/rs.3.rs-3886648/v1] PubMed: none
The tumor-enriched small molecule gambogic amide suppresses glioma by targeting WDR1-dependent cytoskeleton remodeling [ Signal Transduct Target Ther, 2023, 10.1038/s41392-023-01666-3] PubMed: 37935665
Hypoxanthine phosphoribosyl transferase 1 metabolizes temozolomide to activate AMPK for driving chemoresistance of glioblastomas [ Nat Commun, 2023, 14(1):5913] PubMed: 37737247
Hypoxanthine phosphoribosyl transferase 1 metabolizes temozolomide to activate AMPK for driving chemoresistance of glioblastomas [ Nat Commun, 2023, 14(1):5913] PubMed: 37737247
Stellettin B Sensitizes Glioblastoma to DNA-Damaging Treatments by Suppressing PI3K-Mediated Homologous Recombination Repair [ Adv Sci (Weinh), 2023, 10(3):e2205529] PubMed: 36453577

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。

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