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| 50mg |
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Purity: ≥98%
BRL-50481 is a novel, potent and selective inhibitor of phosphodiesterase 7 (PDE7) with IC50s of 0.15, 12.1, 62 and 490 μM for PDE7A, PDE7B, PDE4 and PDE3, respectively. BRL 50481 inhibited the activity of hrPDE7A1 expressed in baculovirus-infected Spodoptera frugiperda 9 cells in a competitive manner (Ki value of 180 nM) and was 416 and 1884 times less potent against PDE3 and 38 and 238 times less potent against PDE4 at a substrate concentration of 1 microM and 50 nM cAMP, respectively. Western blotting identified HSPDE7A1 but not HSPDE7A2 in three human cell types that are implicated in the pathogenesis of chronic obstructive lung disease, namely, CD8+ T-lymphocytes, monocytes, and lung macrophages. BRL 50481 is the first fully documented PDE7 inhibitor that has acceptable selectivity for in vitro studies.
| Targets |
BRL-50481 had a relatively modest potency but did enhance cAMP content (19.1 ± 6.2% of IBMX reaction at 300 μM). While BRL-50481 (30 μM) did not prevent proliferation on its own, it greatly improved rolipram's effects. BRL-50481 (30 μM) improved rolipram's inhibitory action but had no effect on IL-15-induced proliferation. BRL-50481 pretreatment of human monocytes alone for 30 minutes had very little inhibitory effects on TNFα production at all tested doses (about 2 to 10%). Additionally, BRL-50481 improved PGE2's ability to block LPS-induced TNFα release. Neither BRL-50481 nor rolipram (maximum inhibition 52.9±2.7%; pIC30 value 5.33±0.12) significantly affect κB-dependent transcription (5.6±1.9% inhibition at 30 μM). In a concentration-dependent manner, BRL-50481 suppresses PDE7A1-induced LPS-induced TNFα production in monocytes (21.7±1.6% inhibition at 30 μM at the 12-hour time point) [2].
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| ln Vitro |
BRL-50481 had a relatively modest potency but did enhance cAMP content (19.1 ± 6.2% of IBMX reaction at 300 μM). While BRL-50481 (30 μM) did not prevent proliferation on its own, it greatly improved rolipram's effects. BRL-50481 (30 μM) improved rolipram's inhibitory action but had no effect on IL-15-induced proliferation. BRL-50481 pretreatment of human monocytes alone for 30 minutes had very little inhibitory effects on TNFα production at all tested doses (about 2 to 10%). Additionally, BRL-50481 improved PGE2's ability to block LPS-induced TNFα release. Neither BRL-50481 nor rolipram (maximum inhibition 52.9±2.7%; pIC30 value 5.33±0.12) significantly affect κB-dependent transcription (5.6±1.9% inhibition at 30 μM). In a concentration-dependent manner, BRL-50481 suppresses PDE7A1-induced LPS-induced TNFα production in monocytes (21.7±1.6% inhibition at 30 μM at the 12-hour time point) [2].
BRL-50481, chemically known as 3-(N,N-dimethylsulfonamido)-4-methyl-nitrobenzene, is a PDE7 inhibitor with nanomolar potency and is selective against other PDE isoenzymes. [1] In studies using three human cell types implicated in chronic obstructive pulmonary disease (COPD) pathogenesis (CD8+ T-lymphocytes, monocytes, and lung macrophages), BRL-50481 showed no effect on cell proliferation and the generation of TNF-α. [1] BRL-50481 was poorly active in suppressing the proliferation of human CD8+ T-lymphocytes. It only marginally reduced TNF-α release from monocytes and macrophages by 2–11%. Its action was at least additive with the PDE4 inhibitor rolipram. [1] BRL-50481 proved to be a much weaker inhibitor of PDE7B than of PDE7A, displaying an 80-fold higher IC50. [1] A high-throughput screen (HTS) of commercial chemical libraries using a fission yeast-based assay, conducted in comparison with BRL-50481, led to the identification of new PDE7 inhibitors such as BC30. [1] |
| Animal Protocol |
Toxicology studies were conducted in four animal species: mice, rats, dogs, and cynomolgus monkeys.
Studies involved administering BIA 10-2474 for 13 weeks in mice, dogs, and monkeys, and for 26 weeks in rats. In cynomolgus monkeys, administration of a high dose of 100 mg/kg/24 h resulted in observed damage to the medulla oblongata. In rats and mice, very high doses caused cerebral damage, particularly in the hippocampus, accompanied by gliosis and inflammatory cell infiltration. |
| References |
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| Additional Infomation |
BRL-50481 is a C-nitro compound with its benzene ring substituted at positions 1, 2, and 5 with N,N-dimethylaminosulfonyl, methyl, and nitro groups, respectively. It is a selective phosphodiesterase inhibitor that inhibits the PDE7 isoform (Ki = 180 nM). It can function as an EC 3.1.4.53 (3',5'-cyclic adenosine monophosphate phosphodiesterase) inhibitor, an anti-aging agent, and a bone mineral density maintainer. It is a sulfonamide compound, a C-nitro compound, and belongs to the toluene class of compounds.
BRL-50481 has been identified as a novel selective phosphodiesterase 7 (PDE7) inhibitor. [1] Studies have shown that mixed PDE4/PDE7 inhibitors, such as combinations containing BRL-50481, may be more effective and have a better therapeutic index than using PDE4 inhibitors alone (such as rolipram). [1] |
| Molecular Formula |
C9H12N2O4S
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| Molecular Weight |
244.27
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| Exact Mass |
244.052
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| CAS # |
433695-36-4
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| Related CAS # |
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| PubChem CID |
2921148
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| Appearance |
White to off-white solid powder
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| Density |
1.334g/cm3
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| Boiling Point |
391.1ºC at 760 mmHg
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| Melting Point |
73 °C
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| Flash Point |
190.4ºC
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| Index of Refraction |
1.561
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| LogP |
2.757
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
16
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| Complexity |
355
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
IFIUFCJFLGCQPH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C9H12N2O4S/c1-7-4-5-8(11(12)13)6-9(7)16(14,15)10(2)3/h4-6H,1-3H3
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| Chemical Name |
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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