Synonym
PF-184; PF184; PF 184
IUPAC/Chemical Name
8-(2-(3,4-Bis(hydroxymethyl)-3,4-dimethylpyrrolidin-1-yl)-5-chloroisonicotinamido)-1-(4-fluorophenyl)-4,5-dihydro-1H-benzo-[g]indazole-3-carboxamide
InChi Key
JUOWWGNRWRLBSV-UHFFFAOYSA-N
InChi Code
InChI=1S/C32H32ClFN6O4/c1-31(16-41)14-39(15-32(31,2)17-42)26-12-24(25(33)13-36-26)30(44)37-20-7-3-18-4-10-22-27(29(35)43)38-40(28(22)23(18)11-20)21-8-5-19(34)6-9-21/h3,5-9,11-13,41-42H,4,10,14-17H2,1-2H3,(H2,35,43)(H,37,44)
SMILES Code
O=C(C1=NN(C2=CC=C(F)C=C2)C3=C1CCC4=CC=C(NC(C5=C(Cl)C=NC(N6CC(C)(CO)C(C)(CO)C6)=C5)=O)C=C43)N
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
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
Biological target:
(Rac)-PF-184 is a potent inhibitory factor-κB kinase 2 (IKK-2) inhibitor with an IC50 of 37 nM.
In vivo activity:
PHA-408, a low-clearance compound previously shown to be efficacious orally in a rodent model of arthritis, dose-dependently attenuated inhaled lipopolysaccharide-induced cell infiltration and cytokine production. Interestingly, PF-184 produced comparable dose-dependent anti-inflammatory activity by intratracheal administration and was as efficacious as intratracheally administered fluticasone propionate (fluticasone).
Reference: J Pharmacol Exp Ther. 2009 Aug;330(2):377-88. https://pubmed.ncbi.nlm.nih.gov/19478133/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
61.9 |
100.00 |
|
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
619.09
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:
Sommers CD, Thompson JM, Guzova JA, Bonar SL, Rader RK, Mathialagan S, Venkatraman N, Holway VW, Kahn LE, Hu G, Garner DS, Huang HC, Chiang PC, Schindler JF, Hu Y, Meyer DM, Kishore NN. Novel tight-binding inhibitory factor-kappaB kinase (IKK-2) inhibitors demonstrate target-specific anti-inflammatory activities in cellular assays and following oral and local delivery in an in vivo model of airway inflammation. J Pharmacol Exp Ther. 2009 Aug;330(2):377-88. doi: 10.1124/jpet.108.147538. Epub 2009 May 28. PMID: 19478133.
In vivo protocol:
Sommers CD, Thompson JM, Guzova JA, Bonar SL, Rader RK, Mathialagan S, Venkatraman N, Holway VW, Kahn LE, Hu G, Garner DS, Huang HC, Chiang PC, Schindler JF, Hu Y, Meyer DM, Kishore NN. Novel tight-binding inhibitory factor-kappaB kinase (IKK-2) inhibitors demonstrate target-specific anti-inflammatory activities in cellular assays and following oral and local delivery in an in vivo model of airway inflammation. J Pharmacol Exp Ther. 2009 Aug;330(2):377-88. doi: 10.1124/jpet.108.147538. Epub 2009 May 28. PMID: 19478133.
1: Wakenhut F, Allan GA, Fish PV, Fray MJ, Harrison AC, McCoy R, Phillips SC, Ryckmans T, Stobie A, Westbrook D, Westbrook SL, Whitlock GA. N-[(3S)-Pyrrolidin-3-yl]benzamides as novel dual serotonin and noradrenaline reuptake inhibitors: impact of small structural modifications on P-gp recognition and CNS penetration. Bioorg Med Chem Lett. 2009 Sep 1;19(17):5078-81. doi: 10.1016/j.bmcl.2009.07.049. Epub 2009 Jul 31. Erratum in: Bioorg Med Chem Lett. 2010 Jan 15;20(2):772. Ryckmans, Thomas [added]. PubMed PMID: 19647430.
2: Sommers CD, Thompson JM, Guzova JA, Bonar SL, Rader RK, Mathialagan S, Venkatraman N, Holway VW, Kahn LE, Hu G, Garner DS, Huang HC, Chiang PC, Schindler JF, Hu Y, Meyer DM, Kishore NN. Novel tight-binding inhibitory factor-kappaB kinase (IKK-2) inhibitors demonstrate target-specific anti-inflammatory activities in cellular assays and following oral and local delivery in an in vivo model of airway inflammation. J Pharmacol Exp Ther. 2009 Aug;330(2):377-88. doi: 10.1124/jpet.108.147538. Epub 2009 May 28. PubMed PMID: 19478133.
Harrison A, Gardner I, Hay T, Dickins M, Beaumont K, Phipps A, Purkins L, Allan G, Christian R, Duckworth J, Gurrell I, Kempshall S, Savage M, Seymour M, Simpson M, Taylor L, Turnpenny P. Case studies addressing human pharmacokinetic uncertainty using a combination of pharmacokinetic simulation and alternative first in human paradigms. Xenobiotica. 2012 Jan;42(1):57-74. doi: 10.3109/00498254.2011.622418. Epub 2011 Oct 12. PMID: 21992032.
