Oxaprozin

[Description]:

Oxaprozin is an inhibitor of both COX-1 and COX-2 with IC50s of 2.2 μM and 36 μM for human platelet COX-1 and IL-1-stimulated human synovial cell COX-2, respectively. Oxaprozin also inhibits the activation of NF-κB.

[Related Catalog]:

Research Areas >> Inflammation/Immunology

[Target]

COX-1:2.2 μM (IC50)

COX-2:36 μM (IC50)

NF-κB

[In Vitro]

Oxaprozin induces apoptosis in a dose-dependent manner. Oxaprozin increases caspase-3 activity in the activated but not in the resting condition. NF-κB activation is inhibited by 50 μM Oxaprozin. Oxaprozin inhibits activation of the IKK system induced by the reagent IκBα[1]. Oxaprozin dose dependently increase CD40L-treated monocyte apoptosis. 100 μM Oxaprozin induces the strongest proapoptotic effect. 100 μM Oxaprozin significantly increases CD40L-treated monocyte apoptosis. Oxaprozin treatment inhibits CD40L-induced Akt and NF-κB (p65) phosphorylation[2].

[Kinase Assay]

Caspase 3 activity in the presence or absence of 200 ng/mL CD40L plus 1 μg/mL CD40L enhancer and 100 μM Oxaprozin is performed. The enzymatic activity is spectrophotometrically determined for 60 minutes at 405 nm assuming an extinction coefficient of 8.8×103 M1/cm[2].

[Cell Assay]

Purified monocytes are resuspended at 106/mL and cultured for 48 hours. In selective experiments, cells are cultured in the presence or absence of 50 μM PD98059, 1 μM SB203580, 50 μM LY294002, 20 μM SN-50, 50 μM Ac-DEVD-CHO, different doses (5, 10, 50, 100 μM) of Oxaprozin, 100 μM ibuprofen,100 μM indomethacin, or 100 μM naproxene. Percentages of apoptotic cells are measured by both fluorescence microscope and flow cytometer[2].

[References]

[1]. Ottonello L, et al. Delayed apoptosis of human monocytes exposed to immune complexes is reversed byoxaprozin: role of the Akt/IkappaB kinase/nuclear factor kappaB pathway. Br J Pharmacol. 2009 May;157(2):294-306.

[2]. Montecucco F, et al. Oxaprozin-induced apoptosis on CD40 ligand-treated human primary monocytes is associated with the modulation of defined intracellular pathways. J Biomed Biotechnol. 2009;2009:478785.

[Related Small Molecules]

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
467.0±33.0 °C at 760 mmHg

[ Melting Point ]:
154ºC

[ Molecular Formula ]:
C₁₈H₁₅NO₃

[ Molecular Weight ]:
293.317

[ Flash Point ]:
236.2±25.4 °C

[ Exact Mass ]:
293.105194

[ PSA ]:
63.33000

[ LogP ]:
4.19

[ Vapour Pressure ]:
0.0±1.2 mmHg at 25°C

[ Index of Refraction ]:
1.595

Click to get detail MSDS

CHEMICAL IDENTIFICATION

RTECS NUMBER :: RP6990000

CHEMICAL NAME :: 2-Oxazolepropionic acid, 4,5-diphenyl-

CAS REGISTRY NUMBER :: 21256-18-8

LAST UPDATED :: 199612

DATA ITEMS CITED :: 25

MOLECULAR FORMULA :: C18-H15-N-O3

MOLECULAR WEIGHT :: 293.34

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 171 mg/kg/10D-I

TOXIC EFFECTS :: Behavioral - toxic psychosis Cardiac - pulse rate increase, without fall in BP Skin and Appendages - sweating

REFERENCE :: AJPSAO American Journal of Psychiatry. (American Psychiatric Assoc., Circulation Dept., 1400 K St., NW, Washington, DC 20005) V.78- 1921- Volume(issue)/page/year: 152,149,1995

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 4470 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - respiratory depression Gastrointestinal - other changes

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 15,359,1984

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 506 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - respiratory depression Gastrointestinal - other changes

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 15,359,1984

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 2910 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - respiratory depression Gastrointestinal - other changes

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 15,359,1984

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 82 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - respiratory depression Gastrointestinal - other changes

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 15,359,1984

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1210 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - respiratory depression Gastrointestinal - other changes

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 15,359,1984

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 376 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - respiratory depression Gastrointestinal - other changes

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 15,359,1984

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 556 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - respiratory depression Gastrointestinal - other changes

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 15,359,1984

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 93 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - respiratory depression Gastrointestinal - other changes

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 15,359,1984

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: >2 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 15,359,1984

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 200 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - respiratory depression Gastrointestinal - other changes

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 15,359,1984

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: >1 gm/kg

TOXIC EFFECTS :: Gastrointestinal - ulceration or bleeding from stomach Blood - hemorrhage

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 15,359,1984

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 124 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - respiratory depression Gastrointestinal - other changes

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 15,359,1984

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 172 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - respiratory depression Gastrointestinal - other changes

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 15,359,1984

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 248 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - respiratory depression Gastrointestinal - other changes

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 15,359,1984

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: >1 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 15,359,1984

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 36 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - respiratory depression Gastrointestinal - other changes

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 15,359,1984 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 5600 mg/kg/14D-I

TOXIC EFFECTS :: Liver - changes in liver weight Nutritional and Gross Metabolic - weight loss or decreased weight gain Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - hepatic microsomal mixed oxidase (dealkylation, hydroxylation, etc.)

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 18,489,1984 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 220 mg/kg

SEX/DURATION :: female 7-17 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system Reproductive - Specific Developmental Abnormalities - blood and lymphatic systems (including spleen and marrow)

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 15,225,1984

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 10 mg/kg

SEX/DURATION :: female 21 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - other effects to embryo

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 18,528,1984

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 540 mg/kg

SEX/DURATION :: female 17-22 day(s) after conception lactating female 21 day(s) post-birth

TOXIC EFFECTS :: Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 15,265,1984

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1620 mg/kg

SEX/DURATION :: male 8 week(s) pre-mating female 2 week(s) pre-mating - 7 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 15,207,1984

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 39 mg/kg

SEX/DURATION :: female 6-18 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 15,250,1984

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 390 mg/kg

SEX/DURATION :: female 6-18 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 15,250,1984

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 520 mg/kg

SEX/DURATION :: female 6-18 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth)

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 15,250,1984

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ Hazard Codes ]:
Xn: Harmful;Xi: Irritant;

[ Risk Phrases ]:
R20/21/22

[ Safety Phrases ]:
24/25-36/37/39-36-26

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

[ RTECS ]:
RP6990000

[ HS Code ]:
2934999090

Precursor

DownStream

[ HS Code ]: 2934999090

[ Summary ]:
2934999090. other heterocyclic compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Potential therapeutic approach to SAPHO.

Semin. Arthritis Rheum. 29(5) , 332-4, (2000)

Analgesic and Anti-Inflammatory Effects of Oxaprozin and Naproxen Sodium After Removal of Impacted Lower Third Molars: A Randomized, Double-Blind, Placebo-Controlled Crossover Study

J. Oral Maxillofac. Surg. 68(5) , 1018-24, (2010)

Purpose In this study, oxaprozin, a long-acting nonsteroidal anti-inflammatory drug, and naproxen sodium were compared in terms of their effects on edema, pain, and trismus after surgery for impacted ...

Oxaprozin versus diclofenac in NSAID-refractory periarthritis pain of the shoulder.

Curr. Med. Res. Opin. 20(8) , 1279-90, (2004)

To evaluate the efficacy and safety of oxaprozin in comparison with diclofenac in patients with periarthritis pain of the shoulder previously unsuccessfully treated with nonsteroidal anti-inflammatory...

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