Uses
Poseltinib (HM71224) is an orally active, selective, irreversible small molecule Bruton tyrosine kinase (BTK) inhibitor. With an IC50 of 1.95 nM. Poseltinib effectively inhibits the signaling mediated by B cell receptors (BCR), Fc receptors (FcR), and Toll-like receptors (TLR). Poseltinib has anti-inflammatory activity and can be used in the research of rheumatoid arthritis[1][2][3].
in vivo
Poseltinib (3,-30 mg/kg, p.o, once a day, from 18 to 40 weeks) reduces the overactivity of B cells by inhibiting BTK, alleviating the development of systemic lupus erythematosus (SLE) and lupus nephritis (LN)[1].
Poseltinib (1-30 mg/kg p.o, once a day for 2 weeks) improves experimental arthritis in mice [2].
| Animal Model: | MRL/lpr mice and NZB/W F1 mice models[1] |
| Dosage: | 3-30 mg/kg |
| Administration: | p.o |
| Result: | Decreased the spleen weights and prevented skin lesion progression.
Ameliorated renal injury and inflammation and improved the survival rate.
|
| Animal Model: | Collagen-induced arthritis (CIA) mouse model[2] |
| Dosage: | 1-30 mg/kg |
| Administration: | p.o |
| Result: | Reduced the serum IL-6, circulating anti-collagen antibodies and total IgG levels.
Reduced erosive bone changes and prevented bone loss.
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References
[1] Kim YY, et al. HM71224, a selective Bruton's tyrosine kinase inhibitor, attenuates the development of murine lupus. Arthritis Res Ther. 2017 Sep 26;19(1):211. DOI:
10.1186/s13075-017-1402-1[2] Park JK, et al. HM71224, a novel Bruton's tyrosine kinase inhibitor, suppresses B cell and monocyte activation and ameliorates arthritis in a mouse model: a potential drug for rheumatoid arthritis. Arthritis Res Ther. 2016 Apr 18;18:91. DOI:
10.1186/s13075-016-0988-z[3] Byun JY, et al. Target modulation and pharmacokinetics/pharmacodynamics translation of the BTK inhibitor poseltinib for model-informed phase II dose selection. Sci Rep. 2021 Sep 21;11(1):18671. DOI:
10.1038/s41598-021-98255-7
