BRL 50481(Synonyms: N,N,2-三甲基-5-硝基苯磺酰胺) 目录号 : GC15472
A potent, selective inhibitor of PDE7
Sample solution is provided at 25 µL, 10mM.
MOLT-4 cells in 96-well plates are treated for 30 min with BRL-50481 as indicated. The cAMP content is then determined by an immunospecific ELISA. Results are expressed as a percentage of the response affected by 100 μM IBMX.
. Safavi M, et al. New methods for the discovery and synthesis of PDE7 inhibitors as new drugs for neurologicaland inflammatory disorders. Expert Opin Drug Discov. 2013 Jun;8(6):733-51.
BRL 50481 is a selective inhibitor of phosphodiesterase (PDE) 7. At substrate concentrations of 50 nM and 1 ?M, the hydrolysis of cAMP by hrPDE7A1 was inhibited by BRL 50481 with IC50 values of 0.26 and 2.4 ?M, respectively . BRL 50481 is a selective and potent inhibitor of human recombinant PDE7A with an IC50 value of 26 nM .
PDE7 is of a high affinity as a cAMP-specific PDE. PDE7 could be a good treatment target for T cell related diseases, airway diseases or central nervous system (CNS) disorders .
At 1 ?M and 50 nM cAMP, BRL 50481 was a selective inhibitor of hrPDE7A1, with 416 and 1884 times less potencies against PDE3, and 38 and 238 times less potencies against hrPDE4A4, respectively. BRL 50481 did not significantly inhibit PDE1C, PDE1B, PDE5 and PDE2 at concentrations below 100 ?M. BRL 50481 showed a competitive inhibition potency against hrPDE7A1 with a Ki value of 180±10 nM. But in MOLT-4 T cells, BRL 50481 increased the cAMP content with an EC50 >> 100 ?M. The EC80 value of rolipram is about 10 ?M. When the effect of BRL 50481 at concentrations of 10–300 ?M on cAMP mass was examined in the presence of rolipram at a submaximal concentration, the mean concentration-response curve of BRL 50481 was displaced upwards of a significantly greater magnitude, compared to the sum of the cAMP response affected by BRL 50481 and rolipram alone .
Compared to treatment with A-350619 or BRL 50481 alone, the combination of methylene blue and BRL 50481 significantly delayed the onset of action in received mice for jerky movements and convulsion. The combination of methylene blue and exogenously administered BRL 50481 (2 mg/kg, i.p.) significantly had an anti-convulsant activity .
. Smith SJ, Cieslinski LB, Newton R, et al. Discovery of BRL 50481 [3-(N,N-dimethylsulfonamido)-4-methyl-nitrobenzene], a selective inhibitor of phosphodiesterase 7: in vitro studies in human monocytes, lung macrophages, and CD8+ T-lymphocytes. Mol Pharmacol, 2004, 66(6):1679-89.
. Gil C, Campillo NE, Perez DI, et al. PDE7 inhibitors as new drugs for neurological and infl ammatory disorders. Expert Opin Ther Patents, 2008, 18(10):1127-1139.
. Castro A, Jerez MJ, Gil C, et al. CODES, a novel procedure for ligand-based virtual screening: PDE7 inhibitors as an application example. Eur J Med Chem, 2008, 43(7):1349-59.
. Nandhakumar J, Ernest V and Tyagi MG. Evaluation of Seizure Activity After Phospho-diesterase Inhibition (BRL 50481) with Guanylate Cyclase Activation (A-350619) and Inhibition (Methylene blue) in Animal Models of Epilepsy. J Neurol Neurophysiol, 2011, 2:110.
|溶解度||DMF: 20 mg/ml,DMF:PBS (pH7.2) (1:40): 0.02 mg/ml,DMSO: 15 mg/ml,Ethanol: 15 mg/ml||储存条件||Store at -20°C|
储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。
|1 mg||5 mg||10 mg|
|1 mM||4.0938 mL||20.4692 mL||40.9383 mL|
|5 mM||0.8188 mL||4.0938 mL||8.1877 mL|
|10 mM||0.4094 mL||2.0469 mL||4.0938 mL|
|% DMSO % % Tween 80 % saline|
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
3. 以上所有助溶剂都可在 GlpBio 网站选购。