Lomeguatrib

製品コードS8056 バッチS805601

印刷

化学情報

Chemical Structure Synonyms PaTrin-2 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C10H8BrN5OS
分子量 326.17 CAS No. 192441-08-0
Solubility (25°C)* 体外 DMSO 65 mg/mL (199.28 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <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 Lomeguatrib（PaTrin-2）は、5 nMのIC50を持つ強力なO6-alkylguanine-DNA-alkyltransferase阻害剤です。
in vitro

Lomeguatrib inactivates O6-alkylguanine-DNA-alkyltransferase (ATase) with a IC50 10-fold lower than O6-Benzylguanine. This compound inhibits the activity of ATase in Raji cells with IC50 of 10 nM. It effectively inactivates MGMT in MCF-7 cells with IC50 of ~6nM ). 
in vivo

The Lomeguatrib combination results in considerably less toxicity (0/9 vs. 2/9 deaths; 6.84% weight loss vs. 9.48%). This compound alone has no significant effect on tumour growth.

プロトコル(参考用のみ)

キナーゼアッセイ ATases activity assay
The cDNA cloning and overexpression of the human ATase are performed. Purification of the recombinant proteins is achieved by DEAE-cellulose ion-exchange chromatography. The ATase protein is partially purified by ammonium sulfate precipitation (30-60%) and dialyzed against 10 mM Tris-HCl (pH 7.5), 1 mM dithiothreitol (DTT), 2 mM EDTA, 10% glycerol, before loading onto a DEAE-cellulose column. The ATase is then eluted with a 0-0.1 M NaCl gradient. The purified human ATase protein retains activity for more than 1 year when stored at high concentration at -20 ℃ in buffer I [50 mM Tris-HCl (pH 8.3)/3 mM DTT/1 mM EDTA] and could be thawed and refrozen several times without substantial loss of activity.Compounds to be tested are dissolved in DMSO to a final concentration of 10 mM and diluted just before use in buffer I containing 1 mg/mL bovine serum albumin (IBSA). Recombinant ATase is diluted in IBSA and titrated in order that the reaction be conducted under ATase, and not substrate, limiting conditions. In each assay, fixed amounts of ATase (50 -60 fmol) are incubated with varying amounts of O6-benzylguanine, or test compound, in a total volume of 200 μL of IBSA containing 10 μg of calf thymus DNA at 37 ℃ for 1 h. The 3H-methylated DNA substrate (100 μL containing 4 μg of DNA and 100 fmol of this compound is added and incubation continued at 37 ℃for 1 h, until the reaction is completed. Following acid hydrolysis of the DNA, the 3H-methylated protein is recovered and quantitated by liquid scintillation counting. Samples are typically assayed in duplicate and experiments repeated several times.

参考

  • https://pubmed.ncbi.nlm.nih.gov/9857094/
  • https://pubmed.ncbi.nlm.nih.gov/16278661/
  • https://pubmed.ncbi.nlm.nih.gov/10629085/

カスタマーフィードバック

, , Mol Cancer Ther, 2015, 14(5):1236-46.

Data from [Data independently produced by , , Onco Targets Ther, 2018, 11:3671-3684]

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：

MGMT inhibition regulates radioresponse in GBM, GSC, and melanoma [ Sci Rep, 2024, 14(1):12363] PubMed: 38811596
MGMT function determines the differential response of ATR inhibitors with DNA-damaging agents in glioma stem cells for GBM therapy [ Neurooncol Adv, 2024, 6(1):vdad165] PubMed: 38213834
Epigenetic Activation of TUSC3 Sensitizes Glioblastoma to Temozolomide Independent of MGMT Promoter Methylation Status [ Int J Mol Sci, 2023, 24(20)15179] PubMed: 37894860
Heat Shock Protein Inhibitor 17-Allyamino-17-Demethoxygeldanamycin, a Potent Inductor of Apoptosis in Human Glioma Tumor Cell Lines, Is a Weak Substrate for ABCB1 and ABCG2 Transporters [ Pharmaceuticals (Basel), 2021, 14(2)107] PubMed: 33573093
Prolonged unfolded protein reaction is involved in the induction of chronic myeloid leukemia cell death upon oprozomib treatment [ Cancer Sci, 2020, 112(1):133-143] PubMed: 33067904
MutT homologue 1 (MTH1) catalyzes the hydrolysis of mutagenic O6-methyl-dGTP. [ Nucleic Acids Res, 2018, 46(20):10888-10904] PubMed: 30304478
Epigenetic Reprogramming with Antisense Oligonucleotides Enhances the Effectiveness of Androgen Receptor Inhibition in Castration-Resistant Prostate Cancer [ Cancer Res, 2018, 78(20):5731-5740] PubMed: 30135193
CAT3, a prodrug of 13a(S)-3-hydroxyl-6,7-dimethoxyphenanthro[9,10-b]-indolizidine, circumvents temozolomide-resistant glioblastoma via the Hedgehog signaling pathway, independently of O6-methylguanine DNA methyltransferase expression [Ji M Onco Targets Ther, 2018, 11:3671-3684] PubMed: 29983575
MGMT Expression Predicts PARP-Mediated Resistance to Temozolomide. [Erice O, et al. Mol Cancer Ther, 2015, 14(5):1236-46] PubMed: 25777962

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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。