Ampiroxicam (CP 65703) 99464-64-9_COX_Neuronal Signaling_Signaling Pathways_Products

Ampiroxicam (formerly CP 65703; CP65703; CP-65703; Flucam; Ampiroxicamum), a nonsteroidal anti-inflammatory drug (NSAID), is a potent and non-selective inhibitor of cyclooxygenase (COX1/2) enzyme with potential anti-inflammatory activity. It has been approved for use as an anti-inflammatory drug.

Physicochemical Properties

Molecular Formula

C20H21N3O7S

Molecular Weight

447.46

Exact Mass

447.11

CAS #

99464-64-9

Related CAS #

99464-64-9

PubChem CID

2176

Appearance

White to off-white solid powder

Density

1.4±0.1 g/cm3

Melting Point

159-161?C

Index of Refraction

1.630

LogP

3.12

Hydrogen Bond Donor Count

Hydrogen Bond Acceptor Count

Rotatable Bond Count

Heavy Atom Count

Complexity

808

Defined Atom Stereocenter Count

InChi Key

LSNWBKACGXCGAJ-UHFFFAOYSA-N

InChi Code

InChI=1S/C20H21N3O7S/c1-4-28-20(25)30-13(2)29-18-14-9-5-6-10-15(14)31(26,27)23(3)17(18)19(24)22-16-11-7-8-12-21-16/h5-13H,4H2,1-3H3,(H,21,22,24)

Chemical Name

Carbonic acid, ethyl 1-((2-methyl-3-((2-pyridinylamino)carbonyl)-2H-1,2-benzothiazin-4-yl)oxy)ethyl ester, S,S-dioxide

Synonyms

CP-65703; Flucam;CP 65703; CP65703;Ampiroxicamum;

HS Tariff Code

2934.99.9001

Storage

Powder-20°C 3 years

4°C 2 years

In solvent -80°C 6 months

-20°C 1 month

Shipping Condition

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro

In vitro activity: Ampiroxicam (<150 μM) dose-dependently decreases the proliferation of Panc-1 cells. Ampiroxicam (50 μM) results in decreased expression of Sp1, Sp3, Sp4, and VEGFR1 proteins in Panc-1 cells and L3.6pl cells as determined by Western blot analysis. Ampiroxicam (50 μM) results in increased phosphorylation of MAPK1/2 in Panc-1 cells and L3.6pl cells.

Kinase Assay: Panc-1 cells are plated in DME/F12 medium with 5% fetal bovine serum and treated on the next day with vehicle (0.1% DMSO) or various concentrations of Ampiroxicam. Cells are counted at the indicated times with a Coulter Z1 cell counter. Each experiment is done in triplicate, and results are expressed as means, with error bars representing 95% confidence intervals (CIs).

ln Vivo

Ampiroxicam inhibits the stretching response in mice induced by phenylbenzoquinone (PBQ) with maximum protective effect (MPE) of 2 mg/kg. Ampiroxicam inhibits swelling in a dose-responsive manner in the rat foot edema (RFE) assay with ED50 of 28 mg/kg at single oral dose and 7.8 mg/kg at 5 daily oral dose. Ampiroxicam blocks primary and secondary lesion development in rat adjuvant arthritis with ED50 of 2.2 mg/kg and 0.5 mg/kg, respectively. Ampiroxicam (3.2 mg/kg) leads to a plasma concentration of 12 μg/mL at a Tmax of 2 hours for piroxicam derived from ampiroxicam in rats. Ultraviolet-A (UVA)-irradiated 1% Ampiroxicam sensitized in guinea pigs shows positive reaction in the patch testing to UVA-irradiated 1% Ampiroxicam and 1% thiosalicylate (TOS). Concentration of Ampiroxicam is easily reduced by the increase in UVA irradiation doses, as compared with that of piroxicam.

Animal Protocol

Dissolved in 0.1% methylcellulose; 3.2 mg/kg; p.o.

Rats with adjuvant arthritis

References

J Natl Cancer Inst.2006 Jun 21;98(12):855-68;Agents Actions.1993 Jul;39(3-4):157-65.

Additional Infomation

Ampiroxicam is a benzothiazine that is the 1-[(ethoxycarbonyl)oxy]ethyl ether of piroxicam. A prodrug for piroxicam, it is used for the relief of pain and inflammation in musculoskeletal disorders such as rheumatoid arthritis and osteoarthritis. It has a role as a prodrug, an analgesic, a non-steroidal anti-inflammatory drug, an antirheumatic drug and an EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor. It is a benzothiazine, a sulfonamide, an aminopyridine, a monocarboxylic acid amide, an etabonate ester and an acetal. It is functionally related to a piroxicam.

Solubility Data

Solubility (In Vitro)

DMSO:90 mg/mL (201.1 mM)

Water:<1 mg/mL

Ethanol:<1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.59 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 2: ≥ 2.5 mg/mL (5.59 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

(Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.2348 mL	11.1742 mL	22.3484 mL
	5 mM	0.4470 mL	2.2348 mL	4.4697 mL
	10 mM	0.2235 mL	1.1174 mL	2.2348 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.

PeptideDB

Ampiroxicam (CP 65703) 99464-64-9

CAS No.: 99464-64-9

Physicochemical Properties

Biological Activity

Solubility Data