URMC-099

製品コードS7343 バッチS734303

印刷

化学情報

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

C27H27N5
分子量 421.54 CAS No. 1229582-33-5
Solubility (25°C)* 体外 DMSO 84 mg/mL (199.26 mM)
Ethanol 11 mg/mL (26.09 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
4.25mg/ml Taking the 1 mL working solution as an example, add 50 μL of 85 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
Clear solution
5% DMSO 95% Corn oil
0.7mg/ml Taking the 1 mL working solution as an example, add 50 μL of 14 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
* <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 URMC-099 is an orally bioavailable, brain penetrant mixed lineage kinase (MLK) inhibitor with IC50 of 19 nM, 42 nM, 14 nM, and 150 nM, for MLK1, MLK2, MLK3, and DLK, respectively, and also inhibits LRRK2 activity with IC50 of 11 nM. URMC-099 also inhibits ABL1 with IC50 of 6.8 nM. URMC-099 induces autophagy.
in vitro URMC-099 inhibits LPS-induced TNFα release in microglial cells, and HIV-1 Tat-induced release of cytokines in human monocytes. [1] URMC-099 prevents destruction and phagocytosis of cultured neuronal axons by microglia cells. [2] URMC-099 reduces fMLP-induced chemotaxis of wild-type neutrophil in vitro. [3]
in vivo In mice, URMC-099 shows excellent pharmacokinetic properties and improved CNS penetration. [1] In vivo, URMC-099 (10 mg/kg i.p.) reduces inflammatory cytokine production, protects neuronal architecture, and alters the morphologic and ultrastructural response of microglia to HIV-1 Tat exposure. [2] URMC099 significantly reduces recruitment of neutrophils into the peritoneum by fMLP in wild-type mice. [3]

プロトコル(参考用のみ)

キナーゼアッセイ Biochemical assay for the inhibition of kinase activity for MLK3
Myelin basic protein (20 μM final concentration) is dissolved in 20 mM Hepes (pH 7.5) containing 10 μM MgCl2, 1 μM EGTA, 0.02% Brij35, 0.02 mg/ml BSA, 0.1 μM Na3VO4, 2 mM DTT, and 1% DMSO. Activated MLK3 is added and mixed (20 nM final concentration), and inhibitors are added in DMSO. 33P-ATP (specific activity 500 μCi/μL) is delivered into the reaction mixture to initiate the reaction (ATP concentration: 10 μM) and the mixture is incubated at room temperature for 20 minutes. % Activity is determined using a proprietary HOTSPOT™ microfluidic filter binding technology.
動物実験 動物モデル Mice exposed to HIV-1 Tat
投薬量 10 mg/kg twice a day
投与方法 i.p.

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：

PP1γ regulates neuronal insulin signaling and aggravates insulin resistance leading to AD-like phenotypes [ Cell Commun Signal, 2023, 21(1):82] PubMed: 37085815
TrkA expression directs the anti-neoplastic activity of MLK3 inhibitors in triple-negative breast cancer [ Oncogene, 2023, 42(14):1132-1143.] PubMed: 36813855
MLK4 promotes glucose metabolism in lung adenocarcinoma through CREB-mediated activation of phosphoenolpyruvate carboxykinase and is regulated by KLF5 [ Oncogenesis, 2023, 12(1):35] PubMed: 37407566
MLK4 promotes glucose metabolism in lung adenocarcinoma through CREB-mediated activation of phosphoenolpyruvate carboxykinase and is regulated by KLF5 [ Oncogenesis, 2023, 12(1):35] PubMed: 37407566
Systematic analysis of the MAPK signaling network reveals MAP3K-driven control of cell fate [ Cell Syst, 2022, 13(11):885-894.e4] PubMed: 36356576
Antiviral drug screen identifies DNA-damage response inhibitor as potent blocker of SARS-CoV-2 replication [ Cell Rep, 2021, 35(1):108940] PubMed: 33784499
Mixed Lineage Kinase 3 mediates PKG1α impact on cardiac function and controls blood pressure through separate mechanisms. [ JCI Insight, 2021, 6(18)e149075] PubMed: 34324442
Mixed Lineage Kinase 3 mediates PKG1α impact on cardiac function and controls blood pressure through separate mechanisms [ JCI Insight, 2021, 149075] PubMed: 34324442
Synergism between the phosphatidylinositol 3-kinase p110β isoform inhibitor AZD6482 and the mixed lineage kinase 3 inhibitor URMC-099 on the blockade of glioblastoma cell motility and focal adhesion formation [ Cancer Cell Int, 2021, 21(1):24] PubMed: 33407478
Rationalized inhibition of mixed lineage kinase 3 and CD70 enhances life span and antitumor efficacy of CD8 + T cells [ J Immunother Cancer, 2020, 8(2):e000494] PubMed: 32759234

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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