包装 | 价格(元) |
10mM (in 1mL DMSO) | 电议 |
5mg | 电议 |
25mg | 电议 |
100mg | 电议 |
Cell lines | Human monocytes |
Preparation method | Limited solubility. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
Reaction Conditions | 37oC |
Applications | URMC-099 potently and dose-dependently inhibits TNF-α, MCP-1,IL-6, and IL-8 that are crucial to the pathogenesis of HAND (HIV-1 Associated Neurocognitive Disorders). In contrast to the Tat-only treatment, URMC-099 reaches at the lowest drug concentration tested (100 nM) for TNFα and IL-6, and at 300 nM for MCP1. |
Animal models | Tat exposure mouse model |
Dosage form | Injection |
Applications | URMC-099 treatment before and after Tat exposure partially preserves normal Map2 staining at the Tat injection site. As Tat exposure markedly decreases puncta density at the injection site, the puncta density is restored to control levels by URMC-099 treatment. Furthermore, URMC-099 alters the morphology and neuronal interactions of microglia exposed to HIV-1 Tat. |
Other notes | Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
产品描述 | URMC-099 is an orally bioavailable and brain penetrant inhibitor of MLK3 with IC50 value of 14 nM [1]. Mixed Lineage Kinase 3 (MLK3) is a member of the serine/threonine kinase family that regulate MAPK8/JNK signaling cascade and also activates ERK and p38. MLK3 activation can result in the stimulation of cell motility and migration [1] [2]. URMC-099 is a novel and orally bioavailable MLK3 inhibitor. In murine BV-2 microglial cells, URMC-099 inhibited LPS-induced TNFαrelease. In primary human monocytes, URMC-099 inhibited HIV-1 Tat-induced release of cytokines [1]. In neutrophils, URMC-099 reduced chemotaxis induced by fMLP and inhibited fMLP-stimulated F-actin formation [2]. In Tat-injected brains of mice, URMC-099 inhibited up-regulation of phospho-JNK. In HIV-1 Associated Neurocognitive Disorders (HAND) preclinical models, URMC-099 inhibited multiple kinase pathways, including MLK3 and LRRK2 (IC50 = 11 nM). URMC-099 reduced inflammatory cytokine production, protected neuronal architecture, and altered the morphologic and ultrastructural response of microglia to HIV-1 Tat exposure [1] [3]. In wild-type C57Bl/6 mice, URMC-099 inhibited fMLP-induced accumulation of neutrophils in the peritoneum [2]. In infected humanized NOD/SCID/IL2Rγc-/-mice, URMC-099 administered with nanoATV dose-dependently reduced HIV-1p24 viral load and reverse transcriptase activity, as well as the numbers of HIV-1 infected CD4+ T-cells in lymphoid tissues [4]. References: |