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Chemical Structure| 199666-03-0 Chemical Structure| 199666-03-0

Structure of Ro 61-8048
CAS No.: 199666-03-0

Chemical Structure| 199666-03-0

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Ro 61-8048 is an inhibitor of kynurenine 3-hydroxylase which can potently and competitively inhibit kynurenine 3-monooxygenase with Ki value and IC50 value of 4.8 nM and 37 nM, respectively.

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Product Details of Ro 61-8048

CAS No. :199666-03-0
Formula : C17H15N3O6S2
M.W : 421.45
SMILES Code : O=S(C1=CC=C(OC)C(OC)=C1)(NC2=NC(C3=CC=CC([N+]([O-])=O)=C3)=CS2)=O
MDL No. :MFCD11040807
InChI Key :NDPBMCKQJOZAQX-UHFFFAOYSA-N
Pubchem ID :5282337

Safety of Ro 61-8048

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H319
Precautionary Statements:P305+P351+P338

Isoform Comparison

Biological Activity

Target
  • Hydroxylase

    KMO, IC50:37 nM

    KMO, Ki:4.8 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
Trypanosoma brucei brucei (427) 50 μM to 12 pM 48 hours To evaluate the effect of Ro-61-8048 on trypanosome growth, results showed no significant effect on trypanosome proliferation Brain. 2009 May;132(Pt 5):1259-67.
Human hippocampal progenitor cells HPC03A/07 10 μM 10 days Ro 61-8048 partially reversed the IL-1β-induced reduction in neurogenesis. Dcx-positive cells changed from −42% with IL-1β alone to −26% with IL-1β plus inhibitor; MAP2-positive cells changed from −37% with IL-1β alone to −22% with IL-1β plus inhibitor. Neuropsychopharmacology. 2012 Mar;37(4):939-49.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Female CD1 mice Human African trypanosomiasis model Intraperitoneal injection 100 mg/kg Every second day from Day 12 until Day 28 post-infection To assess the effect of Ro-61-8048 on CNS inflammation, results showed a significant reduction in neuroinflammatory response during the late stage of infection Brain. 2009 May;132(Pt 5):1259-67.
Rats Freely-moving rats Intraperitoneal injection 30 and 100 mg/kg Single administration Ro 61-8048 significantly increased extracellular KYNA levels in the NAc shell and VTA, and dose-dependently blocked THC-induced elevations of dopamine in these areas. Nat Neurosci. 2013 Nov;16(11):1652-61
C57BL/6 mice Experimental autoimmune encephalomyelitis (EAE) model Intraperitoneal injection 100 mg/kg Once daily for 7 days Inhibition of KMO enzyme activity increases the synthesis of neuroprotective metabolite KYNA and reduces the synthesis of neurotoxic metabolite QUIN, thereby ameliorating EAE disease severity. J Neuroinflammation. 2020 Jun 6;17(1):176
Rats and squirrel monkeys Nicotine self-administration and relapse models Intraperitoneal injection (rats) and intramuscular injection (squirrel monkeys) Rats: 30, 56, 100 mg/kg; Squirrel monkeys: 10, 20, 30 mg/kg Administered 40 min before sessions, lasting for 3 days Ro 61-8048 significantly reduced nicotine self-administration and blocked nicotine-induced dopamine release in the nucleus accumbens shell. In squirrel monkeys, the effects of Ro 61-8048 were reversed by the positive allosteric modulator of α7nAChRs, PNU120596, indicating the involvement of α7nAChRs in its mechanism of action. Neuropsychopharmacology. 2017 Jul;42(8):1619-1629
C57BL/6J mice Chronic Intermittent Ethanol (CIE) model Intraperitoneal injection 50 mg/kg Single dose, observed for 12 hours Ro 61-8048 reduces ethanol consumption and preference by inhibiting KMO, an effect that involves α7nAChR and depends on the influx of peripheral kynurenine into the brain. Br J Pharmacol. 2022 Jul;179(14):3711-3726
Mice Spared nerve injury (SNI) model Intracerebroventricular injection 0.4 μg/2 μl/day Once daily for two days Ro 61-8048 significantly blocked the increased immobility time in the forced swim test in SNI mice without affecting mechanical allodynia Brain Behav Immun. 2017 Nov;66:94-102
Sprague-Dawley rats Freely moving rats Intraperitoneal injection 30 or 100 mg/kg Single administration, observed for 180 minutes To investigate the effect of Ro 61-8048 on THC-induced increases in extracellular glutamate levels in the NAcS, VTA, and mPFC, results showed that Ro 61-8048 dose-dependently blocked the effects of THC Mol Neurobiol. 2019 May;56(5):3563-3575

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.37mL

0.47mL

0.24mL

11.86mL

2.37mL

1.19mL

23.73mL

4.75mL

2.37mL

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