Mavacoxib (PHA-739521), a long-acting non-steroidal anti-inflammatory drug (NSAID), is a selective, orally active and long-acting cyclooxygenase-2 (COX-2) inhibitor used to treat pain and inflammation associated with degenerative joint disease in dogs.

Physicochemical Properties

Molecular Formula	C16H11F4N3O2S
Molecular Weight	385.3366
Exact Mass	385.05
CAS #	170569-88-7
Related CAS #	Mavacoxib-d4
PubChem CID	9843089
Appearance	White to yellow solid powder
Density	1.5±0.1 g/cm3
Boiling Point	519.8±60.0 °C at 760 mmHg
Flash Point	268.2±32.9 °C
Vapour Pressure	0.0±1.4 mmHg at 25°C
Index of Refraction	1.603
LogP	3.69
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	3
Heavy Atom Count	26
Complexity	579
Defined Atom Stereocenter Count	0
InChi Key	TTZNQDOUNXBMJV-UHFFFAOYSA-N;
InChi Code	InChI=1S/C16H11F4N3O2S/c17-11-3-1-10(2-4-11)14-9-15(16(18,19)20)22-23(14)12-5-7-13(8-6-12)26(21,24)25/h1-9H,(H2,21,24,25);
Chemical Name	4-(5-(4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide;
Synonyms	PHA-739521; PHA739521; PHA 739521; PHA 739,521; PHA739,521; PHA-739,521; Mavacoxib. trade name Trocoxil.;
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	Mavacoxib (0-200 μM; 72 hours) treatment decreased cell viability in a dose-dependent manner in CSKOS, U2OS, REM, K9TCC, and T24 cells. Nevertheless, there are differences in the sensitivity of various cell lines to mavacoxib, with IC50 values ranging from 34.5 μM to 157.7 μM. The cells with IC50 values of 52.6 μM, 89.8 μM, 106.3 μM, 66.6 μM, HT-1376, T24, 5637, REM, LILY, K9TCC, K9TCC-AXA, K9TCC-In, and K9TCC-Sh were U2OS, KTOSA5, CSKOS, REM, and LILY. μM, 54.9μM, 34.5μM, 78.7μM, 50.7μM, 63.4μM, 72.5μM, and 157.7μM are the values mentioned [1]. Treatment of various cell lines with mavacoxib (0-200 μM; 48 hours; KTOSA5, REM, LILY, K9TCC, U2OS, and T24 cells) results in caspase-dependent apoptosis [1]. Mavacoxib (0-75 μM; 24 hours; CSKOS, U2OS, REM, K9TCC, and T24 cells) treatment decreased total Akt expression in U2OS cells and p-Akt expression in CSKOS cells in a dose-dependent manner. When the dosage of Mavacoxib was increased, the expression of p-ERK and p-Akt increased in REM cells, and p-ERK expression increased in K9TCC cells as well [1].
ln Vivo	At a nominal dose of 4 mg/kg BW, dogs with osteoarthritis who took part in the trial were randomized to receive either Mavacoxib and daily carprofen placebo or Mavacoxib placebo and daily carprofen. The first and second dosages in both trials were given two weeks apart, after which they were administered on a monthly basis. Mavacoxib was administered at minimal dosages of 4 mg/kg BW and 2 mg/kg BW in Studies 1 and 2, respectively. In Study 1, seven Mavacoxib doses were administered; in Study 2, however, only five doses were administered. While Mavacoxib was given at any time during the day in Study 1, all Mavacoxib doses were given with food in Study 2 [2].
Cell Assay	Cell Viability Assay[1] Cell Types: CSKOS, U2OS, REM, K9TCC and T24 Cell Tested Concentrations: 0 μM, 0.04 μM, 25 μM, 50 μM, 75 μM, 100 μM, 125 μM, 150 μM, 175 μM, 200 μM Incubation Duration: 72 hrs (hours) Experimental Results: Cell viability diminished in a dose-dependent manner. Apoptosis analysis[1] Cell Types: KTOSA5, REM, LILY, K9TCC, U2OS and T24 Cell Tested Concentrations: 0 μM, 50 μM, 100 μM, 200 μM Incubation Duration: 48 hrs (hours) Experimental Results: Induction of apoptosis in canine and human cancer cell lines Death. Cell viability assay[1] Cell Types: CSKOS, U2OS, REM, K9TCC and T24 Cell Tested Concentrations: 0 μM, 25 μM, 50 μM or 75 μM Incubation Duration: 24 hrs (hours) Experimental Results: In CSKOS cells, p-Akt is downregulated as follows Shown is total Akt in U2OS cells. In REM cells, both p-ERK and p-Akt expression were increased, and p-ERK expression was also increased in K9TCC cells.
References	[1]. The selective cyclooxygenase-2 inhibitor mavacoxib (Trocoxil) exerts anti-tumour effects in vitro independent of cyclooxygenase-2 expression levels. Vet Comp Oncol. 2019 Jun;17(2):194-207. [2]. Population pharmacokinetics of mavacoxib in osteoarthritic dogs. J Vet Pharmacol Ther. 2011 Feb;34(1):1-11.
Additional Infomation	Mavacoxib is a member of the class of pyrazoles that is 1H-pyrazole which is substituted at positions 1, 3 and 5 by 4-sulfamoylphenyl, trifluoromethyl and 4-fluorophenyl groups, respectively. A selective cyclooxygenase 2 inhibitor, it is used in veterinary medicine to treat pain and inflammation in dogs with degenerative joint disease. It has a role as a non-steroidal anti-inflammatory drug, a cyclooxygenase 2 inhibitor and a non-narcotic analgesic. It is a sulfonamide, an organofluorine compound and a member of pyrazoles. Drug Indication For the treatment of pain and inflammation associated with degenerative joint disease in dogs in cases where continuous treatment exceeding one month is indicated.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~259.51 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.40 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 20.8 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: ≥ 2.08 mg/mL (5.40 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (5.40 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 20.8 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	2.5951 mL	12.9756 mL	25.9511 mL
	5 mM	0.5190 mL	2.5951 mL	5.1902 mL
	10 mM	0.2595 mL	1.2976 mL	2.5951 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.