UNC2025 HCl

製品コードS7576 バッチS757602

印刷

化学情報

Chemical Structure Synonyms UNC2025 hydrochloride Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C28H41ClN6O
分子量 513.12 CAS No. 2070015-17-5
Solubility (25°C)* 体外 DMSO 100 mg/mL warmed with 50ºC water bath (194.88 mM)
Ethanol 60 mg/mL warmed with 50ºC water bath (116.93 mM)
Water 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 UNC-2025 HCl is a potent and orally bioavailable dual MER/FLT3 inhibitor with IC50 of 0.74 nM and 0.8 nM, respectively, about 20-fold selectivity over Axl and Tyro3.
in vitro In 697 B-ALL cells, UNC-2025 potently inhibits Mer phosphorylation with IC50 of 2.7 nM. In A549 NSCLC and Molm-14 AML cell lines, UNC-2025 causes significant inhibition of colony formation dependent on Mer8 and Flt3. [1] In H2228 and H1299 cell lines, UNC-2025 inhibits MERTK oncogenic signaling downstream, such as basal and stimulated pAKT and pERK1/2. In four NSCLC cell lines, UNC-2025 also induces apoptotic cell death, and decreases colony formation. [2]
in vivo In mice bearing 697 acute leukemia tumors, UNC-2025 (3 mg/kg, p.o.) shows good solubility and DMPK properties, and results in effective target inhibition. [1] In mice bearing H2228 or A549 tumors, UNC-2025 (50 mg/kg, p.o.) inhibits tumor growth. [2]

プロトコル(参考用のみ)

キナーゼアッセイ IC50 determination
Test compound is dissolved in and diluted with DMSO to achieve 100-fold higher concentration as specified for the compound. The solution is further diluted 25-fold with assay buffer to make the final test compound solution. Reference compounds for assay control were prepared similarly. 5 μL of 4× compound solution, 5 μL of 4× Substrate/ATP/Metal solution, and 10 uL of 2× kinase solution are prepared with assay buffer (20 mM HEPES, 0.01% Triton X-100, 2 mM DTT, pH 7.5) and mixed and incubated in a polypropylene 384 well microplate for 1 or 5 h at room temperature, depending on kinase. 60 μL of Termination Buffer is added to the well. The reaction mixture is applied to a LabChip3000 system, and the product and substrate peptide peaks are separated and quantitated. The kinase reaction is evaluated by the product ratio calculated from peak heights of product (P) and substrate (S) peptides (P/(P+S)). The readout value of reaction control (complete reaction mixture) is set as 0% inhibition, and the readout value of background (Enzyme(-)) is set as 100% inhibition, then the percent inhibition of each test solution is calculated.
動物実験 動物モデル NOD/SCID/gamma mice transplanted with 697 acute leukemia cells
投薬量 3 mg/kg
投与方法 p.o.

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：

Lymph node medulla regulates the spatiotemporal unfolding of resident dendritic cell networks [ Immunity, 2023, 56(8):1778-1793.e10] PubMed: 37463581
Early stress-induced impaired microglial pruning of excitatory synapses on immature CRH-expressing neurons provokes aberrant adult stress responses [ Cell Rep, 2022, 38(13):110600] PubMed: 35354026
EWSR1-WT1 Target Genes and Therapeutic Options Identified in a Novel DSRCT In Vitro Model [ Cancers (Basel), 2021, 13(23)6072] PubMed: 34885181
In vivo microscopy reveals macrophage polarization locally promotes coherent microtubule dynamics in migrating cancer cells [ Nat Commun, 2020, 11(1):3521] PubMed: 32665556
Expression of TAM-R in Human Immune Cells and Unique Regulatory Function of MerTK in IL-10 Production by Tolerogenic DC [ Front Immunol, 2020, 11:564133] PubMed: 33101282
TLR7/8-agonist-loaded Nanoparticles Promote the Polarization of Tumour-Associated Macrophages to Enhance Cancer Immunotherapy [ Nat Biomed Eng, 2018, 2(8):578-588] PubMed: 31015631
Changes in cell morphology guide identification of tubulin as the off-target for protein kinase inhibitors [Hoque M, et al. Pharmacol Res, 2018, 134:166-178] PubMed: 29944980
MERTK Mediates Intrinsic and Adaptive Resistance to AXL-targeting Agents. [ Mol Cancer Ther, 2018, 17(11):2297-2308] PubMed: 30093568
New insights into Notch1 regulation of the PI3K-AKT-mTOR1 signaling axis: targeted therapy of γ-secretase inhibitor resistant T-cell acute lymphoblastic leukemia [ Cell Signal, 2014, 26(1):149-61] PubMed: 24140475

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。