Synonym
PF-9184; PF9184; PF 9184; PF-03549184; PF03549184; PF 03549184
IUPAC/Chemical Name
N-(3',4'-Dichloro[1,1'-biphenyl]-4-yl)-4-hydroxy-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide
InChi Key
VGACSWBJQLLJFB-UHFFFAOYSA-N
InChi Code
InChI=1S/C21H14Cl2N2O4S/c22-16-10-7-13(11-17(16)23)12-5-8-14(9-6-12)24-21(27)19-20(26)15-3-1-2-4-18(15)30(28,29)25-19/h1-11,25-26H,(H,24,27)
SMILES Code
O=C(C1=C(O)C2=CC=CC=C2S(N1)(=O)=O)NC3=CC=C(C4=CC=C(Cl)C(Cl)=C4)C=C3
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, not in water
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
More Info
Inflammation-induced microsomal prostaglandin E synthase-1 (mPGES-1) is the terminal enzyme that synthesizes prostaglandin E(2) (PGE(2)) downstream of cyclooxygenase-2 (COX-2). The efficacy of nonsteroidal anti-inflammatory drugs and COX-2 inhibitors in the treatment of the signs and symptoms of osteoarthritis, rheumatoid arthritis and inflammatory pain, largely attributed to the inhibition of PGE(2) synthesis, provides a rationale for exploring mPGES-1 inhibition as a potential novel therapy for these diseases.
Biological target:
PF-9184 is a potent and highly selective inhibitor of human microsomal prostaglandin E synthase-1 (mPGES-1), with an IC50 of 16.5 nM.
In vitro activity:
PF-9184 potently inhibited recombinant human (rh) mPGES-1 (IC(50)=16.5+/-3.8nM), and had no effect against rhCOX-1 and rhCOX-2 (>6500-fold selectivity). In rationally designed cell systems ideal for determining direct effects of the inhibitors on mPGES-1 function, but not its expression, PF-9184 inhibited PGE(2) synthesis (IC(50) in the range of 0.5-5 microM in serum-free cell and human whole blood cultures, respectively) while sparing the synthesis of 6-keto-PGF(1alpha) (PGF(1alpha)) and PGF(2alpha).
Reference: Biochem Pharmacol. 2010 May 15;79(10):1445-54. https://pubmed.ncbi.nlm.nih.gov/20067770/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMF |
20.0 |
43.35 |
|
| DMSO |
15.0 |
32.52 |
|
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
461.31
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:
1. Raucci F, Saviano A, Casillo GM, Guerra-Rodriguez M, Mansour AA, Piccolo M, Ferraro MG, Panza E, Vellecco V, Irace C, Caso F, Scarpa R, Mascolo N, Alfaifi M, Iqbal AJ, Maione F. IL-17-induced inflammation modulates the mPGES-1/PPAR-γ pathway in monocytes/macrophages. Br J Pharmacol. 2022 May;179(9):1857-1873. doi: 10.1111/bph.15413. Epub 2021 Mar 21. PMID: 33595097.
2. Mbalaviele G, Pauley AM, Shaffer AF, Zweifel BS, Mathialagan S, Mnich SJ, Nemirovskiy OV, Carter J, Gierse JK, Wang JL, Vazquez ML, Moore WM, Masferrer JL. Distinction of microsomal prostaglandin E synthase-1 (mPGES-1) inhibition from cyclooxygenase-2 inhibition in cells using a novel, selective mPGES-1 inhibitor. Biochem Pharmacol. 2010 May 15;79(10):1445-54. doi: 10.1016/j.bcp.2010.01.003. Epub 2010 Jan 11. PMID: 20067770.
In vitro protocol:
1. Raucci F, Saviano A, Casillo GM, Guerra-Rodriguez M, Mansour AA, Piccolo M, Ferraro MG, Panza E, Vellecco V, Irace C, Caso F, Scarpa R, Mascolo N, Alfaifi M, Iqbal AJ, Maione F. IL-17-induced inflammation modulates the mPGES-1/PPAR-γ pathway in monocytes/macrophages. Br J Pharmacol. 2022 May;179(9):1857-1873. doi: 10.1111/bph.15413. Epub 2021 Mar 21. PMID: 33595097.
2. Mbalaviele G, Pauley AM, Shaffer AF, Zweifel BS, Mathialagan S, Mnich SJ, Nemirovskiy OV, Carter J, Gierse JK, Wang JL, Vazquez ML, Moore WM, Masferrer JL. Distinction of microsomal prostaglandin E synthase-1 (mPGES-1) inhibition from cyclooxygenase-2 inhibition in cells using a novel, selective mPGES-1 inhibitor. Biochem Pharmacol. 2010 May 15;79(10):1445-54. doi: 10.1016/j.bcp.2010.01.003. Epub 2010 Jan 11. PMID: 20067770.
1: Mbalaviele G, Pauley AM, Shaffer AF, Zweifel BS, Mathialagan S, Mnich SJ,
Nemirovskiy OV, Carter J, Gierse JK, Wang JL, Vazquez ML, Moore WM, Masferrer JL.
Distinction of microsomal prostaglandin E synthase-1 (mPGES-1) inhibition from
cyclooxygenase-2 inhibition in cells using a novel, selective mPGES-1 inhibitor.
Biochem Pharmacol. 2010 May 15;79(10):1445-54. doi: 10.1016/j.bcp.2010.01.003.
Epub 2010 Jan 11. PubMed PMID: 20067770.
Raucci F, Saviano A, Casillo GM, Guerra-Rodriguez M, Mansour AA, Piccolo M, Ferraro MG, Panza E, Vellecco V, Irace C, Caso F, Scarpa R, Mascolo N, Alfaifi M, Iqbal AJ, Maione F. IL-17-induced inflammation modulates the mPGES-1/PPAR-γ pathway in monocytes/macrophages. Br J Pharmacol. 2022 May;179(9):1857-1873. doi: 10.1111/bph.15413. Epub 2021 Mar 21. PMID: 33595097.
