| Chemical structure | Code NO. |
MT0401 |
 |
Name |
URMC-099 |
Synonym |
URMC099; URMC 099 | |
CAS NO. |
1229582-33-5 | |
Chemical Formula |
C27H27N5 | |
MW |
421.54 | |
Purity |
>98% | |
Solubility(R.T.: 25℃) |
DMSO 84 mg/mL (199.26 mM); Water <1 mg/mL (<1 mM); Ethanol 84 mg/mL (199.26 mM) | |
Stability |
- 20℃, 2 years |
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 withIC50 of 11 nM.
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]
[1] Goodfellow VS, et al. J Med Chem. 2013, 56(20), 8032-8048.
