Stenoparib (E7449)

製品コードS8419 バッチS841901

印刷

化学情報

Chemical Structure Synonyms 2X-121, MGI25036 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C18H15N5O
分子量 317.34 CAS No. 1140964-99-3
Solubility (25°C)* 体外 DMSO 4 mg/mL warmed with 50ºC water bath (12.6 mM)
Water Insoluble
Ethanol Insoluble
* <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 Stenoparib (E7449, 2X-121, MGI25036) is an orally bioavailable, brain penetrable, small molecule dual inhibitor of PARP1/2 and also inhibits PARP5a/5b, otherwise known as tankyrase1 and 2 (TNKS1/2), important regulators of canonical Wnt/β-catenin signaling. It has IC50 values of 1.0 and 1.2 nM for PARP1 and 2, respectively.
in vitro E7449 inhibits PARP enzymatic activity and additionally traps PARP1 onto damaged DNA; a mechanism previously shown to augment cytotoxicity. E7449 inhibits Wnt/β-catenin signaling in colon cancer cell lines, likely through TNKS inhibition. E7449 stabilizes axin and TNKS proteins resulting in β-catenin de-stabilization and significantly alters expression of Wnt target genes. E7449 inhibits TNKS1 and 2 (PARP5a and 5b) with IC50 values of 50-100 nmol/L. Significant inhibitory activity is not observed for PARP3 or PARPs 6-16 (PARP9 and 13 lack activity and PARP4 had minimal signal)[1].
in vivo Chemotherapy is potentiated by E7449 and single agent has significant antitumor activity in BRCA-deficient xenografts. E7449 lacks single agent antitumor activity in vivo. E7449 antitumor activity is increased through combination with MEK inhibition. Treatment with E7449 at 30 or 100 mg/kg in xenografts is well-tolerated without any significant body weight loss or deaths. Treatment with E7449 at 100 mg/kg resulted in significant PARP inhibition that is sustained for at least 12 hours and recovered to basal levels within 24 h[1].

プロトコル(参考用のみ)

細胞アッセイ 細胞株 Human breast cancer cell lines, HCC1143, HCC70, HCC1806, MDA-MB-436, T47D, MDA-MB-157, MDA-MB-231, MDA-MB-468, MDA-MB-453, BT-20 and Hs578T
濃度 --
反応時間 8 days
実験の流れ For proliferation assays cells are plated at low density in 96 well plates. E7449 is added at various concentrations and plates incubated for a total of 8 days; compound and medium are replenished on day 4. Cell growth is assessed.
動物実験 動物モデル C57BL/6 mice
投薬量 30, 100 or 300 mg/kg
投与方法 oral administration

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：

Aggregability of the SQSTM1/p62-based aggresome-like induced structures determines the sensitivity to parthanatos [ Cell Death Discov, 2024, 10(1):74] PubMed: 38346947
Haploinsufficiency of ZNF251 causes DNA-PKcs-dependent resistance to PARP inhibitors in BRCA1-mutated cancer cells [ Res Sq, 2023, rs.3.rs-2688694] PubMed: 37066268
Haploinsufficiency of ZNF251 causes DNA-PKcs-dependent resistance to PARP inhibitors in BRCA1-mutated cancer cells [ Res Sq, 2023, rs.3.rs-2688694] PubMed: 37066268
BAP1 promotes the repair of UV-induced DNA damage via PARP1-mediated recruitment to damage sites and control of activity and stability [ Cell Death Differ, 2022, 10.1038/s41418-022-01024-w] PubMed: 35637285
Stenoparib, an inhibitor of cellular poly (ADP-ribose) polymerases (PARPs), blocks in vitro replication of SARS-CoV-2 variants [ PLoS One, 2022, 17(9):e0272916] PubMed: 36103462
CRISPR screening identifies novel PARP inhibitor classification based on distinct base excision repair pathway dependencies [ bioRxiv, 2021, 10.1101/2020.10.18.333070] PubMed: None
Response of Breast Cancer Cells to PARP Inhibitors Is Independent of BRCA Status. [ J Clin Med, 2020, 30;9(4)] PubMed: 32235451

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。