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Synonyms | HCI-2509 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C19H20ClN3O5S |
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分子量 | 437.90 | CAS No. | 1423715-09-6 | ||||
Solubility (25°C)* | 体外 | DMSO | 38 mg/mL (86.77 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) |
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* <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. |
製品説明 | SP2509 (HCI-2509) is a selective histone demethylase LSD1 inhibitor with IC50 of 13 nM, showing no activity against MAO-A, MAO-B, lactate dehydrogenase and glucose oxidase. SP2509 induces apoptosis and promotes autophagy. |
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in vitro | In AML cells, SP2509 inhibits the association of LSD1 with CoREST, increases promoter-specific H3K4Me3 and induces p53, p21 and C/EBPα. SP2509 also significantly inhibits the colony growth and induces apoptosis of OCI-AML3. In addition, SP2509 induces differentiation of cultured and primary AML cells, and exerts synergistic lethal activity when used in combination with panobinostat. [1] |
in vivo | In mice bearing OCI-AML3 xenografts, SP2509 (25 mg/kg i.p.) significantly improved the survival of the mice, while co-treatment with SP2509 and panobinostat exerts superior in vivo activity. |
キナーゼアッセイ | SP2509 activity assays | |
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Test compounds are diluted to 20 × the desired test concentration in 100% DMSO and 2.5 μL of the diluted drug sampleis added to a black 384-well plate. The LSD1 enzyme stock is diluted 17-fold with assay buffer and 40 μL of the diluted LSD1 enzyme is added to the appropriate wells. Substrate, consisting of horseradish peroxidase, dimethyl K4 peptide corresponding to the first 21 amino acids of the N-terminal tail of histone H3, and 10-acetyl-3,7-dihydroxyphenoxazine is then added to wells. Resorufin is analyzed on an Envision plate reader with an excitation wavelength of 530 nm and an emission wavelength of 595 nm. The activity of SP2509 on the other oxidases is determined by using commercially available kits. The glucose oxidase activity (which also noncovalently binds FAD in an elongate conformation), is determined using the glucose oxidase kit. The MAO assays are performed using the MAO-glo kit with MAO-A and MAO-B. | ||
細胞アッセイ | 細胞株 | OCI-AML3, MV4-11 and MOLM13 cells |
濃度 | ~10 μM | |
反応時間 | 96 hours | |
実験の流れ | Cultured AML cells are treated with SP2509 and/or PS for 96 h. At the end of treatment, cells are washed free of the drugs and 500 cells per condition are plated in methylcellulose and incubated at 37 °C. Colony formation is measured 7–10 days after plating. | |
動物実験 | 動物モデル | NOD/SCID mice bearing OCI-AML3 xenografts |
投薬量 | 20% Cremaphor, 20% DMSO, 60% sterile water | |
投与方法 | i.p. |
Data from [Data independently produced by , , Br J Haematol, 2017, doi: 10.1111/bjh.14983]
Pharmacological inhibition of LSD1 suppresses growth of hepatocellular carcinoma by inducing GADD45B [ MedComm (2020), 2023, 4(3):e269] | PubMed: 37250145 |
LSD1 promotes prostate cancer reprogramming by repressing TP53 signaling independently of its demethylase function [ JCI Insight, 2023, 8(15)e167440] | PubMed: 37440313 |
LSD1 promotes prostate cancer reprogramming by repressing TP53 signaling independently of its demethylase function [ JCI Insight, 2023, 8(15)e167440] | PubMed: 37440313 |
RAS and PP2A activities converge on epigenetic gene regulation [ Life Sci Alliance, 2023, 6(5)e202301928] | PubMed: 36858798 |
Leveraging patient derived models of FGFR2 fusion positive intrahepatic cholangiocarcinoma to identify synergistic therapies [ NPJ Precis Oncol, 2022, 6(1):75] | PubMed: 36274097 |
High-Throughput Drug Library Screening in Primary KMT2A-Rearranged Infant ALL Cells Favors the Identification of Drug Candidates That Activate P53 Signaling [ Biomedicines, 2022, 10(3)638] | PubMed: 35327440 |
SP2509, a Selective Inhibitor of LSD1, Suppresses Retinoblastoma Growth by Downregulating β-catenin Signaling [ Invest Ophthalmol Vis Sci, 2022, 63(3):20] | PubMed: 35297943 |
Targeting LSD1 suppresses stem cell-like properties and sensitizes head and neck squamous cell carcinoma to PD-1 blockade [ Cell Death Dis, 2021, 12(11):993] | PubMed: 34689153 |
KRT6A Promotes Lung Cancer Cell Growth and Invasion Through MYC-Regulated Pentose Phosphate Pathway [ Front Cell Dev Biol, 2021, 9:694071] | PubMed: 34235156 |
SP2509, an inhibitor of LSD1, exerts potential antitumor effects by targeting the JAK/STAT3 signaling [ Acta Biochim Biophys Sin (Shanghai), 2021, gmab083] | PubMed: 34169322 |
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。