WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H522360
CAS#: 199666-03-0
Description: Ro61-8048 is a potent Kynurenine hydroxylase inhibitor (Ki = 4.8 nM, IC50 = 37 nM). Ro 61-8048 improves dystonia in a genetic model of paroxysmal dyskinesia. Ro 61-8048 may be potentially useful for the treatment of dyskinesias. Ro 61-8048 could be a new avenue to reduce neuronal loss in brain ischemia.
Hodoodo Cat#: H522360
Name: Ro61-8048
CAS#: 199666-03-0
Chemical Formula: C17H15N3O6S2
Exact Mass: 421.04
Molecular Weight: 421.440
Elemental Analysis: C, 48.45; H, 3.59; N, 9.97; O, 22.78; S, 15.21
Synonym: Ro61-8048; Ro 61-8048; Ro-61-8048; Ro618048; Ro 618048; Ro-618048
IUPAC/Chemical Name: 3,4-dimethoxy-N-(4-(3-nitrophenyl)thiazol-2-yl)benzenesulfonamide
InChi Key: NDPBMCKQJOZAQX-UHFFFAOYSA-N
InChi Code: InChI=1S/C17H15N3O6S2/c1-25-15-7-6-13(9-16(15)26-2)28(23,24)19-17-18-14(10-27-17)11-4-3-5-12(8-11)20(21)22/h3-10H,1-2H3,(H,18,19)
SMILES Code: O=S(C1=CC=C(OC)C(OC)=C1)(NC2=NC(C3=CC=CC([N+]([O-])=O)=C3)=CS2)=O
Appearance: Light yellow solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | Ro 61-8048 is an inhibitor of kynurenine 3-hydroxylase with an IC50 of 37 nM. |
| In vitro activity: | In vitro experiments to investigate the effects of Ro-61-8048 on T. b. brucei showed that addition of the inhibitor to the culture medium in concentrations ranging from 50 μM to 12 pM had no demonstrable effect of trypanosome growth in culture. When the control, pentamidine, was added to the medium trypanosome growth was rapidly inhibited with the trypanocidal drug showing an IC50 of 0.2 nM and confirming the validity of the negative result gained from inclusion of the inhibitor (Fig. 6). These results suggest that the anti-inflammatory action of Ro-61-8048 is due to a direct effect of the inhibitor on the host cells and not a secondary response to parasite destruction. Reference: Brain. 2009 May;132(Pt 5):1259-67. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2677800/ |
| In vivo activity: | Whether drug-seeking and relapse behaviour can be modified by the metabolic shift of endogenous kynurenine pathway was investigated. An inhibitor of kynurenine-3-monooxygenase (KMO) Ro61-8048 (4 and 40 mg/kg) was tested in a behavioural rat model for drug seeking and relapse—the alcohol deprivation effect (ADE) model in long-term alcohol-drinking rats and the model of cue-induced reinstatement of alcohol- and cocaine-seeking behaviour. Relapse-like alcohol drinking during the ADE was abolished by repeated intraperitoneal administration of Ro61-8048. Cue-induced reinstatement of both alcohol- and cocaine-seeking behaviour was also abolished by administration of Ro61-8048. Reference: Psychopharmacology (Berl). 2016 Sep;233(18):3449-59. https://link.springer.com/article/10.1007%2Fs00213-016-4384-9 |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 49.8 | 118.14 | |
| DMF | 25.0 | 59.32 | |
| DMF:PBS (pH 7.2) (1:1) | 0.5 | 1.19 | |
| Ethanol | 1.6 | 3.73 |
The following data is based on the product molecular weight 421.44 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Rodgers J, Stone TW, Barrett MP, Bradley B, Kennedy PG. Kynurenine pathway inhibition reduces central nervous system inflammation in a model of human African trypanosomiasis. Brain. 2009 May;132(Pt 5):1259-67. doi: 10.1093/brain/awp074. Epub 2009 Mar 31. PMID: 19339256; PMCID: PMC2677800. 2. Vengeliene V, Cannella N, Takahashi T, Spanagel R. Metabolic shift of the kynurenine pathway impairs alcohol and cocaine seeking and relapse. Psychopharmacology (Berl). 2016 Sep;233(18):3449-59. doi: 10.1007/s00213-016-4384-9. Epub 2016 Jul 30. PMID: 27475106. |
| In vitro protocol: | 1. Rodgers J, Stone TW, Barrett MP, Bradley B, Kennedy PG. Kynurenine pathway inhibition reduces central nervous system inflammation in a model of human African trypanosomiasis. Brain. 2009 May;132(Pt 5):1259-67. doi: 10.1093/brain/awp074. Epub 2009 Mar 31. PMID: 19339256; PMCID: PMC2677800. |
| In vivo protocol: | 1. Vengeliene V, Cannella N, Takahashi T, Spanagel R. Metabolic shift of the kynurenine pathway impairs alcohol and cocaine seeking and relapse. Psychopharmacology (Berl). 2016 Sep;233(18):3449-59. doi: 10.1007/s00213-016-4384-9. Epub 2016 Jul 30. PMID: 27475106. |
1: Beconi MG, Yates D, Lyons K, Matthews K, Clifton S, Mead T, Prime M, Winkler D, O'Connell C, Walter D, Toledo-Sherman L, Munoz-Sanjuan I, Dominguez C. Metabolism and pharmacokinetics of JM6 in mice: JM6 is not a prodrug for Ro-61-8048. Drug Metab Dispos. 2012 Dec;40(12):2297-306. doi: 10.1124/dmd.112.046532. Epub 2012 Aug 31. PubMed PMID: 22942319.
2: Yang J, Li W, Zhou Z, Yang C. Is Ro 61-8048 a potential fast-acting antidepressant? J Neurol Sci. 2012 Apr 15;315(1-2):180; author reply 181-2. doi: 10.1016/j.jns.2011.11.037. Epub 2011 Dec 12. PubMed PMID: 22169632.
3: Ouattara B, Belkhir S, Morissette M, Dridi M, Samadi P, Grégoire L, Meltzer LT, Di Paolo T. Implication of NMDA receptors in the antidyskinetic activity of cabergoline, CI-1041, and Ro 61-8048 in MPTP monkeys with levodopa-induced dyskinesias. J Mol Neurosci. 2009 Jun;38(2):128-42. doi: 10.1007/s12031-008-9137-8. Epub 2008 Aug 14. PubMed PMID: 18704766.
4: Hamann M, Sander SE, Richter A. Effects of the kynurenine 3-hydroxylase inhibitor Ro 61-8048 after intrastriatal injections on the severity of dystonia in the dt sz mutant. Eur J Pharmacol. 2008 May 31;586(1-3):156-9. doi: 10.1016/j.ejphar.2008.02.052. Epub 2008 Feb 29. PubMed PMID: 18353306.
5: Richter A, Hamann M. The kynurenine 3-hydroxylase inhibitor Ro 61-8048 improves dystonia in a genetic model of paroxysmal dyskinesia. Eur J Pharmacol. 2003 Sep 30;478(1):47-52. PubMed PMID: 14555184.
6: Chiarugi A, Moroni F. Quinolinic acid formation in immune-activated mice: studies with (m-nitrobenzoyl)-alanine (mNBA) and 3,4-dimethoxy-[-N-4-(-3-nitrophenyl)thiazol-2yl]-benzenesul fonamide (Ro 61-8048), two potent and selective inhibitors of kynurenine hydroxylase. Neuropharmacology. 1999 Aug;38(8):1225-33. PubMed PMID: 10462134.
7: Cozzi A, Carpenedo R, Moroni F. Kynurenine hydroxylase inhibitors reduce ischemic brain damage: studies with (m-nitrobenzoyl)-alanine (mNBA) and 3,4-dimethoxy-[-N-4-(nitrophenyl)thiazol-2yl]-benzenesulfonamide (Ro 61-8048) in models of focal or global brain ischemia. J Cereb Blood Flow Metab. 1999 Jul;19(7):771-7. PubMed PMID: 10413032.
