Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
Compound
Query: UMLS:C0003864 (
arthritis
)
69,039
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The effects on proteoglycan metabolism and aggregation of several nonsteroidal antiinflammatory drugs commonly used in the treatment of
arthritis
were examined in cultures of normal canine articular cartilage.
Fenoprofen
and ibuprofen inhibited net proteoglycan synthesis in a concentration-dependent fashion. At concentrations in the culture medium comparable to plasma concentrations seen in patients after oral administration in humans, net proteoglycan synthesis in the presence of these drugs averaged 72% and 86% of the control values, respectively (P < 0.01). In contrast, indomethacin and sulindac sulfoxide had no effect on proteoglycan synthesis, while sulindac sulfide stimulated synthesis in a non-concentration dependent fashion (average, 13%). In the presence of ibuprofen or sulindac sulfide, catabolism of sulfated glycosaminoglycans was the same as that in control cartilage, while fenoprofen decreased the rate of degradation slightly. The proportion of newly synthesized proteoglycans existing as aggregates and the average hydrodynamic size of disaggregated proteoglycans were unaffected by ibuprofen, indomethacin, sulindac sulfide, or sulindac sulfoxide.
Fenoprofen
, on the other hand, interfered with the ability of the cartilage hyaluronic acid to interact with proteoglycans to form aggregates, whereas it had no effect on the in vitro association of proteoglycans with hyaluronic acid from umbilical cord.
Arthritis
Rheum 1980 Sep
PMID:Effects of some nonsteroidal antiinflammatory drugs on proteoglycan metabolism and organization in canine articular cartilage. 741 50
The efficiency of drug research and development has paradoxically declined over the last decades despite major scientific and technological advances, promoting new cost-effective strategies such as drug repositioning by systematic screening for new actions of known drugs. Here, we performed a screening for positive allosteric modulators (PAMs) at melanocortin (MC) receptors. The non-steroidal anti-inflammatory drug fenoprofen, but not the similar compound ibuprofen, presented PAM activity at MC
3
, MC
4
, and MC
5
receptors. In a model of
inflammatory arthritis
, fenoprofen afforded potent inhibition while ibuprofen was nearly inactive.
Fenoprofen
presented anti-arthritic actions on cartilage integrity and synovitis, effects markedly attenuated in Mc3r-/- mice.
Fenoprofen
displayed pro-resolving properties promoting macrophage phagocytosis and efferocytosis, independently of cyclooxygenase inhibition. In conclusion, combining repositioning with advances in G-protein coupled receptor biology (allosterism) may lead to potential new therapeutics. In addition, MC
3
PAMs emerged as a viable approach to the development of innovative therapeutics for joint diseases.
...
PMID:Old drugs with new skills: fenoprofen as an allosteric enhancer at melanocortin receptor 3. 2785 32
