URMC-099

製品コードS7343 バッチS734302

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 6 mg/mL (14.23 mM)
Water 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 URMC-099は、経口バイオアベイラビリティを有する脳透過性の混合系統キナーゼ（MLK）阻害剤で、MLK1、MLK2、MLK3、DLKに対するIC50値はそれぞれ19 nM、42 nM、14 nM、150 nMであり、また、LRRK2活性をIC50 11 nMで阻害します。URMC-099はABL1もIC50 6.8 nMで阻害します。URMC-099はオートファジーを誘導します。
in vitro URMC-099 inhibits LPS-induced TNFα release in microglial cells, and HIV-1 Tat-induced release of cytokines in human monocytes. This compound prevents destruction and phagocytosis of cultured neuronal axons by microglia cells. It reduces fMLP-induced chemotaxis of wild-type neutrophil in vitro.
in vivo In mice, URMC-099 shows excellent pharmacokinetic properties and improved CNS penetration. In vivo, this compound (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. It significantly reduces recruitment of neutrophils into the peritoneum by fMLP in wild-type mice.

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.

参考

  • https://pubmed.ncbi.nlm.nih.gov/24044867/
  • https://pubmed.ncbi.nlm.nih.gov/23761895/
  • https://pubmed.ncbi.nlm.nih.gov/24389043/

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
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
Anthocyanins attenuate neuroinflammation through the suppression of MLK3 activation in a mouse model of perioperative neurocognitive disorders. [ Brain Res, 2020, 1726:146504] PubMed: 31654642

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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