Please use this identifier to cite or link to this item:
https://doi.org/10.1186/ar2365
DC Field | Value | |
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dc.title | Cartilage preservation by inhibition of Janus kinase 3 in two rodent models of rheumatoid arthritis | |
dc.contributor.author | Milici, A.J | |
dc.contributor.author | Kudlacz, E.M | |
dc.contributor.author | Audoly, L | |
dc.contributor.author | Zwillich, S | |
dc.contributor.author | Changelian, P | |
dc.date.accessioned | 2020-10-20T04:44:10Z | |
dc.date.available | 2020-10-20T04:44:10Z | |
dc.date.issued | 2008 | |
dc.identifier.citation | Milici, A.J, Kudlacz, E.M, Audoly, L, Zwillich, S, Changelian, P (2008). Cartilage preservation by inhibition of Janus kinase 3 in two rodent models of rheumatoid arthritis. Arthritis Research and Therapy 10 (1) : R14. ScholarBank@NUS Repository. https://doi.org/10.1186/ar2365 | |
dc.identifier.issn | 14786354 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/177981 | |
dc.description.abstract | Introduction: CP-690550 is a small molecule inhibitor of Janus kinase 3 (JAK3), a critical enzyme in the signaling pathway of multiple cytokines (interleukin (IL)-2, -7, -15 and -21) that are important in various T cell functions including development, activation and homeostasis. The purpose of this study was to evaluate CP-690550 in murine collagen-induced (CIA) and rat adjuvant-induced (AA) models of rheumatoid arthritis (RA). Methods: CIA and AA were induced using standard protocols and animals received the JAK3 inhibitor via osmotic mini-pump infusion at doses ranging from 1.5-15 mg/kg/day following disease induction. Arthritis was assessed by clinical scores in the CIA models and paw swelling monitored using a plethysmometer in the AA model until study conclusion, at which time animals were killed and evaluated histologically. Results: CP-690550 dose-dependently decreased endpoints of disease in both RA models with greater than 90% reduction observed at the highest administered dose. An approximate ED50 of approximately 1.5 mg/kg/day was determined for the compound based upon disease endpoints in both RA models examined and corresponds to CP-690550 serum levels of 5.8 ng/ml in mice (day 28) and 24 ng/ml in rats (day 24). The compound also reduced inflammatory cell influx and joint damage as measured histologically. Animals receiving a CP-690550 dose of 15 mg/k/d showed no histological evidence of disease. Conclusion: The efficacy observed with CP-690550 in CIA and AA suggests JAK3 inhibition may represent a novel therapeutic target for the treatment of RA. © 2008 Milici et al.; licensee BioMed Central Ltd. | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.source | Unpaywall 20201031 | |
dc.subject | 4 [n [1 (2 cyano 1 oxoethyl) 4 methyl 3 piperidinyl] n methylamino]pyrrolo[2,3 d]pyrimidine | |
dc.subject | interleukin 6 | |
dc.subject | Janus kinase 3 | |
dc.subject | tumor necrosis factor antibody | |
dc.subject | collagen | |
dc.subject | CP 690,550 | |
dc.subject | CP-690,550 | |
dc.subject | enzyme inhibitor | |
dc.subject | immunological adjuvant | |
dc.subject | interleukin 6 | |
dc.subject | Janus kinase 3 | |
dc.subject | pyrimidine derivative | |
dc.subject | pyrrole derivative | |
dc.subject | adjuvant arthritis | |
dc.subject | animal cell | |
dc.subject | animal experiment | |
dc.subject | animal model | |
dc.subject | animal tissue | |
dc.subject | article | |
dc.subject | chondroprotection | |
dc.subject | controlled study | |
dc.subject | DBA 1 mouse | |
dc.subject | dose response | |
dc.subject | drug blood level | |
dc.subject | drug dose comparison | |
dc.subject | drug efficacy | |
dc.subject | drug megadose | |
dc.subject | drug targeting | |
dc.subject | enzyme inhibition | |
dc.subject | Lewis rat | |
dc.subject | low drug dose | |
dc.subject | male | |
dc.subject | mouse | |
dc.subject | nonhuman | |
dc.subject | paw edema | |
dc.subject | protein blood level | |
dc.subject | rat | |
dc.subject | rheumatoid arthritis | |
dc.subject | scoring system | |
dc.subject | animal | |
dc.subject | arthritis | |
dc.subject | articular cartilage | |
dc.subject | blood | |
dc.subject | DBA mouse | |
dc.subject | drug antagonism | |
dc.subject | enzymology | |
dc.subject | immunology | |
dc.subject | pathology | |
dc.subject | rheumatoid arthritis | |
dc.subject | Adjuvants, Immunologic | |
dc.subject | Animals | |
dc.subject | Arthritis, Experimental | |
dc.subject | Arthritis, Rheumatoid | |
dc.subject | Cartilage, Articular | |
dc.subject | Collagen | |
dc.subject | Dose-Response Relationship, Drug | |
dc.subject | Enzyme Inhibitors | |
dc.subject | Interleukin-6 | |
dc.subject | Janus Kinase 3 | |
dc.subject | Male | |
dc.subject | Mice | |
dc.subject | Mice, Inbred DBA | |
dc.subject | Pyrimidines | |
dc.subject | Pyrroles | |
dc.subject | Rats | |
dc.subject | Rats, Inbred Lew | |
dc.type | Article | |
dc.contributor.department | DUKE-NUS MEDICAL SCHOOL | |
dc.description.doi | 10.1186/ar2365 | |
dc.description.sourcetitle | Arthritis Research and Therapy | |
dc.description.volume | 10 | |
dc.description.issue | 1 | |
dc.description.page | R14 | |
Appears in Collections: | Elements Staff Publications |
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