1187460-81-6
1187460-81-6 structure
- Name: PF 184
- Chemical Name: 8-[[2-[(3S,4R)-3,4-bis(hydroxymethyl)-3,4-dimethylpyrrolidin-1-yl]-5-chloropyridine-4-carbonyl]amino]-1-(4-fluorophenyl)-4,5-dihydrobenzo[g]indazole-3-carboxamide
- CAS Number: 1187460-81-6
- Molecular Formula: C32H32ClFN6O4
- Molecular Weight: 619.09
- Catalog: Signaling Pathways NF-κB IKK
- Create Date: 2017-12-27 09:38:30
- Modify Date: 2024-01-15 18:14:56
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PF-184 is a potent inhibitory factor-κB kinase 2 (IKK-2) inhibitor with an IC50 of 37 nM. PF-184 has anti-inflammatory effects[1].
| Name | 8-[[2-[(3S,4R)-3,4-bis(hydroxymethyl)-3,4-dimethylpyrrolidin-1-yl]-5-chloropyridine-4-carbonyl]amino]-1-(4-fluorophenyl)-4,5-dihydrobenzo[g]indazole-3-carboxamide |
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| Synonyms | pf 184 |
| Description | PF-184 is a potent inhibitory factor-κB kinase 2 (IKK-2) inhibitor with an IC50 of 37 nM. PF-184 has anti-inflammatory effects[1]. |
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| Related Catalog | |
| Target |
IKK-2:37 nM (IC50) |
| In Vitro | PF-184 has slow dissociation kinetics with a T1/2 of 6.7 h from rhIKK-2, very low oral bioavailability (5%), high intravenous clearance (59 ml/min/kg), and high P450 metabolism in human liver microsomes[1]. PF-184 binds tightly to endogenous IKK-2 and shows extended inhibition of kinase activity and cytokine production[1]. PF-184 shows a concentration-dependent inhibition on LPS- and IL-1β-induced production of inflammatory mediators in a variety of human disease-relevant cells[1]. PF-184 (0.001-10 µM, 1 h) inhibits IL-1β-induced TNF-α in a concentration-dependent manner with maximal efficacies of 94% and relative potencies of 163 nM[1]. PF-184 inhibits LPS-induced cytokine production from rat alveolar macrophages and blocked p65 nuclear translocation[1]. |
| In Vivo | PF-184 (0.3-2.5 mg; i.t.; once) blocks neutrophil infiltration and BAL cell cytokine production[1]. Animal Model: Fasted male Sprague-Dawley rats (350 g) placed into a chamber connected to a large volume nebulizer filled with 20 ml of 1 mg/mL solution of LPS[1] Dosage: 0.3–2.5 mg Administration: Nano suspension and administered intratracheally in a volume of 100 µL, 60 min before aerosolized LPS Result: Resulted in a comparable attenuation of total cell and PMN cell infiltration 4 h after LPS exposure. Dose-dependently inhibited cell infiltration with EC50 values of 1 mg. Dose-dependently suppressed BAL fluid TNF- and PGE2 levels comparable with cell infiltration. Inhibited p65 translocation. Showed long-lasting activity. |
| References |
| Molecular Formula | C32H32ClFN6O4 |
|---|---|
| Molecular Weight | 619.09 |
| Exact Mass | 618.21600 |
| PSA | 151.08000 |
| LogP | 5.32700 |