Poseltinib

• CAT Number: I008829
• CAS Number: 1353552-97-2
• Molecular Formula: C26H26N6O3
• Molecular Weight: 470.52
• Purity: ≥95%
• Synonyms: N-[3-[2-[4-(4-methylpiperazin-1-yl)anilino]furo[3,2-d]pyrimidin-4-yl]oxyphenyl]prop-2-enamide
• InChI: InChI=1S/C26H26N6O3/c1-3-23(33)27-19-5-4-6-21(17-19)35-25-24-22(11-16-34-24)29-26(30-25)28-18-7-9-20(10-8-18)32-14-12-31(2)13-15-32/h3-11,16-17H,1,12-15H2,2H3,(H,27,33)(H,28,29,30)
• InChIKey: LZMJNVRJMFMYQS-UHFFFAOYSA-N
• SMILES: CN1CCN(CC1)C2=CC=C(C=C2)NC3=NC4=C(C(=N3)OC5=CC=CC(=C5)NC(=O)C=C)OC=C4

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].
Poseltinib (0.1-100 nM, 30 min) inhibits BCR and FcR signaling in B cells[1].
Poseltinib (1-1000 nM, 1 h) inhibits the phosphorylation of Btk and its downstream molecules such as PLCγ2, in activated Ramos B lymphoma cells in a dose-dependent manner.
Inhibits the production of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β by human monocytes, and osteoclast formation by human monocytes in primary human B cells [2].BTK, AKT, and PLCγ2 in PBMCs cells[3].
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].

Reference

[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.
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[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.
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[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.
 [Content Brief]