1229582-33-5

Basic information

• Product Name: URMC-099
• Synonyms: URMC-099;3-(1H-indol-5-yl)-5-[4-[(4-methyl-1-piperazinyl)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridine;3-(1H-indol-5-yl)-5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridine URMC-099
• CAS NO: 1229582-33-5
• Molecular Formula: C₂₇H₂₇N₅
• Molecular Weight: 421.53678
• Product Categories: Inhibitors
• Mol File: 1229582-33-5.mol
• Article Data: 5

Chemical Properties

• Appearance: /
• Density: 1.256±0.06 g/cm3(Predicted)
• Storage Temp.: -20°C
• Solubility: Soluble in DMSO (>25 mg/ml)
• PKA: 13.49±0.40(Predicted)
• 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.
• CAS DataBase Reference: URMC-099(CAS DataBase Reference)
• NIST Chemistry Reference: URMC-099(1229582-33-5)
• EPA Substance Registry System: URMC-099(1229582-33-5)

Safety Data

• Hazardous Substances Data: 1229582-33-5(Hazardous Substances Data)

Usage

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

Upstream product

• 1351477-60-5 3-iodo-5-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine 
• 144104-59-6 1H-indole-5-boronic acid 
• 1351477-58-1 5-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-pyrrolo[2,3-b]pyridine 
• 87199-17-5 4-formylphenylboronic acid, 
• 1351477-59-2 3-iodo-5-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-pyrrolo[2,3-b]pyridine 
• 109-01-3 1-methyl-piperazine 
• 1229583-72-5 4-(3-(1H-indol-5-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)benzaldehyde 
• 1229583-70-3 5-bromo-3-(1H-indol-5-yl)-1-(p-toluenesulfonyl)-1H-pyrrolo[2,3-b]pyridine 
• 875639-15-9 5-bromo-3-iodo-1-(4-methylbenzene-1-sulfonyl)-1H-pyrrolo[2,3-b]pyridine 
• 757978-18-0 3-iodo-5-bromo-1H-pyrrolo[2,3-b]-pyridine 
• 183208-35-7 5-bromo-1H-pyrrolo[2,3-b]pyridine 

Relevant articles and documents

Discovery of a series of 1H-pyrrolo[2,3-b]pyridine compounds as potent TNIK inhibitors

In an in-house screening, 1H-pyrrolo[2,3-b]pyridine scaffold was found to have high inhibition on TNIK. Several series of compounds were designed and synthesized, among which some compounds had potent TNIK inhibition with IC50 values lower than 1 nM. Some compounds showed concentration-dependent characteristics of IL-2 inhibition. These results provided new applications of TNIK inhibitors and new prospects of TNIK as a drug target.

MIXED LINEAGE KINASE INHIBITORS FOR HIV/AIDS THERAPIES

Disclosed are methods for treating an individual infected with a retrovirus that comprise administering to the individual effective amounts of a mixed lineage kinase inhibitor and antiretroviral drug. In further aspects, disclosed are methods for treating an individual infected with a retrovirus that comprises administering an antiretroviral drug formulated into a crystalline nanoparticle comprising a surfactant, and a MLK inhibitor. Still further disclosed are methods for treating an individual infected with a retrovirus that comprises administering a composition comprising both an antiretroviral and MLK inhibitor formulated into a crystalline nanoparticle, which comprises a surfactant. Still further disclosed are compositions that comprise an antiretroviral drug, a MLK inhibitor, and a surfactant, wherein the composition is a crystalline nanoparticle. Compostions comprising MLK inhibitors with other drugs in nanoparticulate form, and methods of there use, are also disclosed.

BICYCLIC HETEROARYL KINASE INHIBITORS AND METHODS OF USE

Provided are compounds having an inhibitory effect on kinases including Mixed Lineage Kinases. Also provided are pharmaceutical compositions, methods of preparing the compounds, synthetic intermediates, and methods of using the compounds, independently or in combination with other therapeutic agents, for treating diseases and conditions that are affected by Mixed Lineage Kinase inhibition. Also provided are methods of treatment of neuropsychiatric disorders that comprise the inhibition of Mixed Lineage Kinases.