| Identification | Back Directory | [Name]
URMC-099 | [CAS]
1229582-33-5 | [Synonyms]
RMC099
CS-1776
URMC-099
URMC-099;URMC 099
3-(1H-indol-5-yl)-5-[4-[(4-methyl-1-piperazinyl)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridine
1H-?Pyrrolo[2,?3-?b]?pyridine, 3-?(1H-?indol-?5-?yl)?-?5-?[4-?[(4-?methyl-?1-?piperazinyl)?methyl]?phenyl]?-
3-(1H-indol-5-yl)-5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridine URMC-099 | [Molecular Formula]
C27H27N5 | [MDL Number]
MFCD28168077 | [MOL File]
1229582-33-5.mol | [Molecular Weight]
421.54 |
| Chemical Properties | Back Directory | [density ]
1.256±0.06 g/cm3(Predicted) | [storage temp. ]
-20°C | [solubility ]
Soluble in DMSO (>25 mg/ml) | [form ]
solid | [pka]
13.49±0.40(Predicted) | [color ]
Off-white | [Stability:]
Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months. |
| Hazard Information | Back Directory | [Description]
URMC-099 (1229582-33-5) is a potent (IC50 = 14 nM), brain penetrant mixed-lineage kinase 3 inhibitor (MLK3). It also potently inhibits FLT3 (4 nM in vitro, but 560 nM in vivo), LRRK2 (11 nM), and ABL1 (3 nM).1 URMC-099 displayed neuroprotective effects in HIV-associated neurocognitive disorders2 and facilitated microglial amyloid-β degradation and clearance in mouse models.3,4 URMC-099 increased CD8+ T cells in mice and increased the CD8+GZMB+ T cell population in blood mononuclear cells isolated from breast cancer patients.5 | [Uses]
URMC-099 is an orally bioavailable MLK3 inhibitor used in the treatment of Parkinson’s disease and HIV-1 associated neurocognitive disorders. | [References]
1) Goodfellow et al. (2013), Discovery, synthesis, and characterization of an orally bioavailable, brain penetrant inhibitor of mixed lineage kinase 3; J. Med. Chem. 56 8032
2) Marker et al. (2013), The new small-molecule mixed-lineage kinase 3 inhibitor URMC-099 is neuroprotective and anti-inflammatory in models of human immunodeficiency virus-associated neurocognitive disorders; J. Neurosc. 33 9998
3) Dong et al. (2016), The mixed-lineage kinase 3 inhibitor URMC-099 facilitates microglial amyloid-β degradation; J. Neuroinflammation 13 184
4) Kiyota et al. (2018), URMC-099 facilitates amyloid-β clearance in a murine model of Alzheimer’s disease; J. Neuroinflammation 15 137
5) Kumar et al. (2020), Mixed lineage kinase 3 inhibition induces T cell activation and cytotoxicity; Proc. Natl. Acad. Sci. USA 9 34567 |
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