Ro 61-8048 是口服有效的、选择性的犬尿氨酸 3-羟

Ro 61-8048 is an orally active and selective inhibitor of kynurenine 3-hydroxylase, with an IC₅₀ of 37 nM. Ro 61-8048 provokes a significant increase of extracellular kynurenic acid concentrations^[1].

In gerbils, a dose of 30 µmol/kg po (12.64 µg/kg Ro 61-8048, compound 16) leads to inhibition of the cerebral enzyme which peaked after 2h (∼85% inhibition) and persisted for up to 8 h^[1].
Ro 61-8048 (0.1-100 μM) strongly reduces QUIN neo-formation, suggesting that, in vitro, kynurenine hydroxylase activity is required for QUIN neosynthesis^[3].

Ro 61-8048 (50, 100 and 150 mg/kg i.p.) significantly reduces the severity of dystonia in dt^sz hamsters without leading to marked central side effects^[2].
Ro 61-8048 (100 mg/kg i.p.) provokes a two- to threefold increase of the endogeneous broad spectrum glutamate receptor antagonist kynurenic acid in the striatum, cerebellum and brainstem of mutant hamsters^[2].

421.45

C₁₇H₁₅N₃O₆S₂

199666-03-0

固体

Light yellow to yellow

Room temperature in continental US; may vary elsewhere.

• [1]. S Röver, et al. Synthesis and biochemical evaluation of N-(4-phenylthiazol-2-yl)benzenesulfonamides as high-affinity inhibitors of kynurenine 3-hydroxylase. J Med Chem. 1997 Dec 19;40(26):4378-85.  [Content Brief]

  [2]. Melanie Hamann, et al. 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.  [Content Brief]

  [3]. AlbertoChiarugi, et al. Quinolinic acid formation in immune-activated mice: studies with (m-nitrobenzoyl)-alanine (mNBA) and 3,4-dimethoxy-[-N-4-(-3-nitrophenyl) thiazol-2yl]-benzenesulfonamide (Ro 61-8048), two potent and selective inhibitors of kynureni