1144035-53-9 PF-8380 AKSci X5984
 
 
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  X5984    
PF-8380
, 98% (HPLC)
 
4-[3-Oxo-3-(2-oxo-2,3-dihydrobenzoxazol-6-yl)propyl]piperazine-1-carboxylic acid 3,5-dichlorobenzyl ester




IDENTITY
CAS Number:1144035-53-9
MDL Number:MFCD20527274
MF:C22H21Cl2N3O5
MW:478.33
SPECIFICATIONS & PROPERTIES
Purity:98% (HPLC)
Spectra:NMR, FT-IR, MS, HPLC
Physical Form: White to Yellow Solid
Melting Point:117-123°C
Density:1.419
Long-Term Storage:Store long-term at -20°C

BIOLOGICAL INFO
Solubility:DMSO
Application(s):Autotaxin inhibitor

REVIEW

 PF 8380 is a potent inhibitor of autotaxin, the enzyme responsible for the production of lysophosphatidic acid (LPA) from lysophosphatidyl choline (LPC), which is up-regulated in many inflammatory conditions, including cancer, arthritis, and multiple sclerosis. LPA signaling causes angiogenesis, mitosis, cell proliferation, and cytokine secretion. Inhibition of autotaxin may have anti-inflammatory properties in a variety of diseases. PF-8380 [6-(3-(piperazin-1-yl)propanoyl)benzo[d]oxazol-2(3H)-one] has an IC(50) of 2.8 nM in an isolated enzyme assay and 101 nM in human whole blood. PF-8380 has adequate oral bioavailability and exposures required for in vivo testing of autotaxin inhibition. Autotaxin's role in producing LPA in plasma and at the site of inflammation was tested in a rat air pouch model. The specific inhibitor PF-8380, dosed orally at 30 mg/kg, provided >95% reduction in both plasma and air pouch LPA within 3 h, indicating autotaxin is a major source of LPA during inflammation. At 30 mg/kg PF-8380 reduced inflammatory hyperalgesia with the same efficacy as 30 mg/kg naproxen. Inhibition of plasma autotaxin activity correlated with inhibition of autotaxin at the site of inflammation and in ex vivo whole blood. Furthermore, a close pharmacokinetic/pharmacodynamic relationship was observed, which suggests that LPA is rapidly formed and degraded in vivo. PF-8380 can serve as a tool compound for elucidating LPA's role in inflammation.

REFERENCES
[1]Gierse J, Thorarensen A, Beltey K, Bradshaw-Pierce E, Cortes-Burgos L, Hall T, Johnston A, Murphy M, Nemirovskiy O, Ogawa S, Pegg L, Pelc M, Prinsen M, Schnute M, Wendling J, Wene S, Weinberg R, Wittwer A, Zweifel B, Masferrer J. A novel autotaxin inhibitor reduces lysophosphatidic acid levels in plasma and the site of inflammation, Journal of Pharmacology and Experimental Therapeutics (2010), 334(1), 310-317.
[2] Mize, Catrina D.; Abbott, Ashley M.; Gacasan, Samantha B.; Parrill, Abby L.; Baker, Daniel L. Ligand-based autotaxin pharmacophore models reflect structure-based docking results, Journal of Molecular Graphics & Modelling (2011), 31, 76-86.
[3] St-Coeur PD, Ferguson D, Morin P Jr, Touaibia M. PF-8380 and closely related analogs: synthesis and structure-activity relationship towards autotaxin inhibition and glioma cell viability. Arch Pharm (Weinheim). 2013 Feb;346(2):91-7.
[4] St-Coeur, Patrick-Denis; Ferguson, Dean; Morin, Pier, Jr.; Touaibia, Mohamed; PF-8380 and Closely Related Analogs: Synthesis and Structure-Activity Relationship towards Autotaxin Inhibition and Glioma Cell Viability, Archiv der Pharmazie (Weinheim, Germany) (2013), 346(2), 91-97.

GHS

Pictograms

Signal Word
Warning

Hazard Statements
H315; H319; H335

Precautionary Statements
P261; P264; P271; P280; P302+P352; P304+P340; P305+P351+P338; P312; P321; P332+P313; P337+P313; P362; P403+P233; P405; P501


Current as of July 18, 2019


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