受注:045-509-1970 |
技術サポート:[email protected] 平日9:00〜18:00 1営業日以内にご連絡を差し上げます |
Synonyms | OTS167 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
|
化学式 | C25H28Cl2N4O2 |
|||
分子量 | 487.42 | CAS No. | 1431697-89-0 | |
Solubility (25°C)* | 体外 | DMSO | 2 mg/mL warmed with 50ºC water bath (4.1 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. |
製品説明 | OTSSP167 (OTS167) is a highly potent MELK (maternal embryonic leucine zipper kinase) inhibitor with IC50 of 0.41 nM. |
---|---|
in vitro | OTSSP167 inhibits A549, T47D, DU4475, and 22Rv1 cancer cells, in which MELK is highly expressed, with IC50 values of 6.7, 4.3, 2.3, and 6.0 nM, respectively. OTSSP167 inhibited the phosphorylation of PSMA1 (proteasome subunit alpha type 1) and DBNL (drebrin-like), which are novel MELK substrates and are important for stem-cell characteristics and invasiveness. OTSSP167 suppresses mammosphere formation of breast cancer cells through the inhibition of PSMA1 phosphorylation. [1] |
in vivo | OTSSP167 exhibits significant tumor growth suppression in xenograft studies using breast, lung, prostate, and pancreas cancer cell lines in mice by both intravenous and oral administration. In MDA-MB-231 model, intravenous administration of OTSSP167 at 20 mg/kg once every two days results in TGI of 73% The oral administration at 10 mg/kg once a day reveals TGI of 72%. OTSSP167 for multiple cancer types in dose-dependent and MELK-dependent manners with no or a little body-weight loss. [1] |
特徴 | MELK-selective inhibitor. |
キナーゼアッセイ | in vitro kinase assay | |
---|---|---|
MELK recombinant protein (0.4 μg) is mixed with 5 μg of each substrate in 20 μL of kinase buffer containing 30 mM Tris-HCl (pH), 10 mM DTT, 40 mM NaF, 10 mM MgCl2, 0.1 mM EGTA with 50 μM cold-ATP and 10 Ci of [γ-32P]ATP for 30 min at 30 °C. The reaction is terminated by addition of SDS sample buffer and boiled for 5 min prior to SDS-PAGE. The gel is dried and autoradiographed with intensifying screens at room temperature. OTSSP167 (final concentration of 10 nM) is dissolved in DMSO and added to kinase buffer before the incubation. | ||
細胞アッセイ | 細胞株 | A549, T47D, DU4475, and 22Rv1, HT1197 |
濃度 | 0.005-0.1 μM | |
反応時間 | 72 h | |
実験の流れ | Cell Counting Kit-8 | |
動物実験 | 動物モデル | MDA-MB-231, A549, DU145 xenografts |
投薬量 | 1 mg/kg , 5mg/kg ,10 mg/kg, 20 mg/kg | |
投与方法 | oral |
p53 isoform expression promotes a stemness phenotype and inhibits doxorubicin sensitivity in breast cancer [ Cell Death Dis, 2023, 14(8):509] | PubMed: 37553320 |
p53 isoform expression promotes a stemness phenotype and inhibits doxorubicin sensitivity in breast cancer [ Cell Death Dis, 2023, 14(8):509] | PubMed: 37553320 |
Remarkable Synergy When Combining EZH2 Inhibitors with YM155 Is H3K27me3-Independent [ Cancers (Basel), 2022, 15(1)208] | PubMed: 36612203 |
Microtubule affinity regulating kinase 4 promoted activation of the NLRP3 inflammasome-mediated pyroptosis in periodontitis [ J Oral Microbiol, 2022, 14(1):2015130] | PubMed: 34992737 |
Wild-type IDH1 inhibits the tumor growth through degrading HIF-α in renal cell carcinoma [ Int J Biol Sci, 2021, 17(5):1250-1262] | PubMed: 33867843 |
MELK promotes Endometrial carcinoma progression via activating mTOR signaling pathway. [ EBioMedicine, 2020, 51:102609] | PubMed: 31915116 |
Kinome expression profiling to target new therapeutic avenues in multiple myeloma. [ Haematologica, 2020, 105(3):784-795] | PubMed: 31289205 |
Catalytic Domain Plasticity of MKK7 Reveals Structural Mechanisms of Allosteric Activation and Diverse Targeting Opportunities [ Cell Chem Biol, 2020, 27(10):1285-1295.e4] | PubMed: 32783966 |
Inhibition of MELK produces potential anti-tumour effects in bladder cancer by inducing G1/S cell cycle arrest via the ATM/CHK2/p53 pathway. [ J Cell Mol Med, 2020, 24(2):1804-1821] | PubMed: 31821699 |
Mass Spectrometry-Based Selectivity Profiling Identifies a Highly Selective Inhibitor of the Kinase MELK That Delays Mitotic Entry in Cancer Cells [ J Biol Chem, 2020, 295(8):2359-2374] | PubMed: 31896573 |
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。