Lornoxicam (Chlortenoxicam; Xefo; Lornoxicamum; Xefocam; TS-110; Ro 13-9297; TS110), a non-steroidal anti-inflammatory drug (NSAID), is a potent COX-1/COX-2 inhibitor with potential anti-inflammatory activity. It has been approved as an anti-inflammatory drug to treat pain, osteoarthritis, and rheumatoid arthritis. Lornoxicam, a new nonsteroidal anti-inflammatory drug (NSAID) belonging to the oxicam class. By intensively inhibiting COX-1 and COX-2, this drug, both in oral and parenteral formulations, shows remarkable analgesic, anti-inflammatory and antipyretic properties

Physicochemical Properties

Molecular Formula	C13H10CLN3O4S2
Molecular Weight	371.82
Exact Mass	370.98
CAS #	70374-39-9
Related CAS #	Lornoxicam-d4;1216527-48-8
PubChem CID	54690031
Appearance	Light yellow to yellow solid powder
Density	1.7±0.1 g/cm3
Melting Point	225-230°C (dec.)
Index of Refraction	1.741
LogP	2.18
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	2
Heavy Atom Count	23
Complexity	634
Defined Atom Stereocenter Count	0
InChi Key	WLHQHAUOOXYABV-UHFFFAOYSA-N
InChi Code	InChI=1S/C13H10ClN3O4S2/c1-17-10(13(19)16-9-4-2-3-5-15-9)11(18)12-7(23(17,20)21)6-8(14)22-12/h2-6,18H,1H3,(H,15,16,19)
Chemical Name	6-chloro-4-hydroxy-2-methyl-1,1-dioxo-N-pyridin-2-ylthieno[2,3-e]thiazine-3-carboxamide
Synonyms	Ro 13-9297; TS 110;Ro-13-9297; TS-110;Ro13-9297; TS110;Chlortenoxicam; Lornoxicam; Chlortenoxicam; Xefo; Lornoxicamum; Xefocam; xefocam
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: Lornoxicam is as effective as the opioid analgesics morphine, pethidine (meperidine) and tramadol in relieving postoperative pain following gynaecological or orthopaedic surgery, and as effective as other NSAIDs after oral surgery. Lornoxicam is also as effective as other NSAIDs in relieving symptoms of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, acute sciatica and low back pain. Cell Assay: Studies on intact human cells showed that lornoxicam intensively inhibit COX-1 and COX-2 with the lowest IC50 among a large panel of NSAIDs tested. Similar findings were obtained in the whole blood for COX-1/-2. In addition lornoxicam suppressed NO formation in a dose-dependently manner with an IC50 of 65 μM.
ln Vivo	Lornoxicam dose relatedly reduces the total number of c-Fos-LI neurons with the strongest effect corresponding to the 75% reduction for the highest dose of 9 mg/kg, and the 45% reduction for the low dose of 0.3 mg/kg. Lornoxicam (0.1, 0.3 mg/kg, 1 mg/kg, 3 mg/kg and 9 mg/kg, i.v.) significantly reduces the number of c-Fos-LI neurons in both superficial (24%, 33%, 53%, 54%, and 63% reduction, respectively) and deep (28%, 48%, 62%, 69% and 79% reduction, respectively) laminae of the dorsal horn of the spinal cord. Lornoxicam reduces hyperalgesia with an effective dose that provides 50% inhibition (ED50) of 0.083 mg/kg, 3.9 mg/kg and 4.3 mg/kg respectively in a chronic rat model of arthritis. Lornoxicam significantly reduces the PGE2 level in paw exudate and the cerebrospinal fluid in rats. Lornoxicam 0.16 mg/kg, celecoxib 4 mg/kg and loxoprofen 2.4 mg/kg significantly reduces hyperalgesia to a similar extent in acute oedematous rats.
Animal Protocol	0.1, 0.3 mg/kg, 1 mg/kg, 3 mg/kg and 9 mg/kg, i.v. Rats
ADME/Pharmacokinetics	Absorption, Distribution and Excretion Lornoxicam is absorbed rapidly and almost completely from the GI tract (90-100%). Metabolism / Metabolites Lornoxicam is metabolized completely by cyp 2C9 with the principal metabolite being 5'-hydroxy-lornoxicam and only negligible amounts of intact lornoxicam are excreted unchanged in the urine. Approximately 2/3 of the drug is eliminated via the liver and 1/3 via the kidneys in the active form. Lornoxicam has known human metabolites that include 5'-Hydroxylornoxicam. Biological Half-Life 3-5 hours
Toxicity/Toxicokinetics	Protein Binding Lornoxicam is 99% bound to plasma proteins (almost exlusively to serum albumin).
References	Drugs.1996 Apr;51(4):639-57;Inflammopharmacology.1997;5(4):331-41.
Additional Infomation	Lornoxicam is a thienothiazine-derived monocarboxylic acid amide obtained by formal condensation of the carboxy group of 6-chloro-4-hydroxy-2-methylthieno[2,3-e][1,2]thiazine-3-carboxylic acid 1,1-dioxide with the amino group of 2-aminopyridine. Used for the treatment of pain, primarily resulting from inflammatory diseases of the joints, osteoarthritis, surgery, sciatica and other inflammations. It has a role as a non-steroidal anti-inflammatory drug, a non-narcotic analgesic and an antipyretic. It is a thienothiazine, a member of pyridines, a monocarboxylic acid amide, an organochlorine compound and a heteroaryl hydroxy compound. Lornoxicam (chlortenoxicam) is a new nonsteroidal anti-inflammatory drug (NSAID) of the oxicam class with analgesic, anti-inflammatory and antipyretic properties. Lornoxicam differs from other oxicam compounds in its potent inhibition of prostaglandin biosynthesis, a property that explains the particularly pronounced efficacy of the drug. Lornoxicam is approved for use in Japan. Lornoxicam is an orally bioavailable oxicam and non-steroidal anti-inflammatory drug (NSAID), with analgesic, anti-pyretic, anti-thrombotic and anti-inflammatory activities. Upon oral administration, lornoxicam binds to and inhibits the activity of the cyclooxygenase enzymes (COX) type 1 (COX-1) and type 2 (COX-2). This blocks COX-mediated signaling pathways, which leads to reduced prostaglandin and thromboxane production and decreased pain, fever and inflammation. Drug Indication For the treatment of acute mild to moderate pain, as well as pain and inflammation of the joints caused by certain types of rheumatic diseases. Mechanism of Action Like other NSAIDS, lornoxicam's anti-inflammatory and analgesic activity is related to its inhibitory action on prostaglandin and thromboxane synthesis through the inhibition of both COX-1 and COX-2. This leads to the reduction of inflammation, pain, fever, and swelling, which are mediated by prostaglandins. However, the exact mechanism of lornoxicam, like that of the other NSAIDs, has not been fully determined. Pharmacodynamics Lornoxicam is a non-steroidal anti-inflammatory drug (NSAID) that belongs to the oxicam class. As with other NSAIDS, lornoxicam is a potent inhibitor of the cyclooxgenase enzymes, which are responsible for catalyzing the formation of prostaglandins (act as messenger molecules in the process of inflammation) and thromboxane from arachidonic acid. Unlike some NSAIDS, lornoxicam's inhibition of cyclooxygenase does not lead to an increase in leukotriene formation, meaning that arachidonic acid is not moved to the 5-lipoxygenase cascade, resulting in the minimization of the risk of adverse events.

Solubility Data

Solubility (In Vitro)

DMSO:3 mg/mL (8.1 mM) Water:<1 mg/mL Ethanol:<1 mg/mL

Solubility (In Vivo)

Chemical Name:6-chloro-4-hydroxy-2-methyl-1,1-dioxo-N-pyridin-2-ylthieno[2,3-e]thiazine-3-carboxamide InChi Key:WLHQHAUOOXYABV-UHFFFAOYSA-NInChi Code:InChI=1S/C13H10ClN3O4S2/c1-17-10(13(19)16-9-4-2-3-5-15-9)11(18)12-7(23(17,20)21)6-8(14)22-12/h2-6,18H,1H3,(H,15,16,19)SMILES Code:CN1C(=C(C2=C(S1(=O)=O)C=C(S2)Cl)O)C(=O)NC3=CC=CC=N3  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.6895 mL	13.4474 mL	26.8947 mL
	5 mM	0.5379 mL	2.6895 mL	5.3789 mL
	10 mM	0.2689 mL	1.3447 mL	2.6895 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.