Domatinostat (4SC-202)

製品コードS7555 バッチS755501

印刷

化学情報

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

C23H21N5O3S
分子量 447.51 CAS No. 910462-43-0
Solubility (25°C)* 体外 DMSO 89 mg/mL (198.87 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 Domatinostat (4SC-202) is a selective class I HDAC inhibitor with IC50 of 1.20 μM, 1.12 μM, and 0.57 μM for HDAC1, HDAC2, and HDAC3, respectively. Also displays inhibitory activity against Lysine specific demethylase 1 (LSD1). Phase 1.
in vitro In HeLa cells, Domatinostat (4SC-202) induces hyperacetylation of histone H3 with EC50 of 1.1 μM. It induces a G2/M cell cycle arrest by interfering with the normal development of the mitotic spindle and causing collapsed spindle apparatus and multiple nucleation centres. In addition, this compound shows a broad anti-proliferative activity towards human cancer cell lines with a mean IC50 of 0.7 μM. [1]
in vivo Domatinostat (4SC-202) has high oral bioavailability in vivo, and shows high metabolic stability and a low plasma clearance. It (120 mg/kg p.o.) shows pronounced and robust anti-tumor activity in both A549 NSCLC xenograft and RKO27 colon carcinoma model. [1]

プロトコル(参考用のみ)

細胞アッセイ 細胞株 CRC lines (HT-29, HCT-116, HT-15, and DLD-1)
濃度 0.1, 1, 5, 10 μM
反応時間 72 hours
実験の流れ

CRC cell lines (HT-29, HCT-116, HCT-15, and DLD1), the primary human colon cancer cells, or primary human colon epithelial cells were treated with applied concentrations of Domatinostat (4SC-202), and then further cultured for indicated time. Cell survival was tested by MTT assay or trypan blue staining assay; cell proliferation was tested by clonogenicity assay. Expression of listed proteins was tested by Western blots.
動物実験 動物モデル A549 NSCLC xenograft model and RKO27 colon carcinoma model
投薬量 120 mg/kg
投与方法 p.o.

参考

  • http://www.4sc.de/wp-content/uploads/4SC-202-Poster-EORTC-Berlin-2010.pdf
  • https://pubmed.ncbi.nlm.nih.gov/26831668/

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：

Epigenetic and molecular coordination between HDAC2 and SMAD3-SKI regulates essential brain tumour stem cell characteristics [ Nat Commun, 2023, 14(1):5051] PubMed: 37598220
Epigenetic and molecular coordination between HDAC2 and SMAD3-SKI regulates essential brain tumour stem cell characteristics [ Nat Commun, 2023, 14(1):5051] PubMed: 37598220
Single-cell dissection of Merkel cell carcinoma heterogeneity unveils transcriptomic plasticity and therapeutic vulnerabilities [ Cell Rep Med, 2023, 4(7):101101] PubMed: 37421947
Domatinostat Targets the FOXM1-Survivin Axis to Reduce the Viability of Ovarian Cancer Cells Alone and in Combination with Chemotherapeutic Agents [ Int J Mol Sci, 2023, 24(13)10817] PubMed: 37445993
Domatinostat Targets the FOXM1-Survivin Axis to Reduce the Viability of Ovarian Cancer Cells Alone and in Combination with Chemotherapeutic Agents [ Int J Mol Sci, 2023, 24(13)10817] PubMed: 37445993
HDAC Inhibition Restores Response to HER2-Targeted Therapy in Breast Cancer via PHLDA1 Induction [ Int J Mol Sci, 2023, 24(7)6228] PubMed: 37047202
Targeting the USP7/RRM2 axis drives senescence and sensitizes melanoma cells to HDAC/LSD1 inhibitors [ Cell Rep, 2022, 40(12):111396] PubMed: 36130505
HDAC Class I Inhibitor Domatinostat Preferentially Targets Glioma Stem Cells over Their Differentiated Progeny [ Int J Mol Sci, 2022, 23(15)8084] PubMed: 35897656
Reduction of Metastasis via Epigenetic Modulation in a Murine Model of Metastatic Triple Negative Breast Cancer (TNBC) [ Cancers (Basel), 2022, 14(7)1753] PubMed: 35406526
Complexities in the role of acetylation dynamics in modifying inducible gene activation parameters [ Nucleic Acids Res, 2021, 49(22):12744-12756] PubMed: 34850951

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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