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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, Ki:4.8 nM

    KMO, IC50:37 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 PMC2677800
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. PMC3280640

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 PMC2677800
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. PMC3835353
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. PMC7276083
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. PMC5518900
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. PMC9314579
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 PMC5650931
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 PMC6393222

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

References

 

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