Poseltinib

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Chemical Structure| 1353552-97-2 同义名 : HM71224;LY3337641
CAS号 : 1353552-97-2
货号 : A587798
分子式 : C26H26N6O3
纯度 : 98+%
分子量 : 470.523
MDL号 : MFCD31729279
存储条件:

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月

溶解度 :

DMSO: 105 mg/mL(223.16 mM),配合低频超声助溶,注意:DMSO长时间开封后,会吸水并导致溶解能力下降,请避免使用长期开封的DMSO

动物实验配方:
生物活性
描述 Bruton’s tyrosine kinase (BTK), a member of the Tec family of tyrosine kinases and expressed in B cells, macrophages, and monocytes but not in T cells, plays a crucial role in signaling through the B cell receptor (BCR) and the Fcγ receptor (FcγR) in B cells and myeloid cells, respectively[3]. Poseltinib, an orally active, selective and irreversible BTK inhibitor with an IC50 value of 1.95 nM[4]. Poseltinib effectively suppressed splenic B220+GL7+, B220+CD138+, and B220+CD69+B cell counts, and anti-dsDNA IgG and reduced splenomegaly and lymph node enlargement. It also prevented skin lesions caused by lupus development, ameliorated renal inflammation and damage with increased blood urea nitrogen and creatinine, and decreased proteinuria. Furthermore, Poseltinib also decreased mortality from lupus development in both mouse models. Those results indicated that inhibition of BTK by Poseltinib effectively reduced B cell hyperactivity and significantly attenuated the development of SLE (Systemic lupus erythematosus) and LN (lupus nephritis) in rodent SLE models[4].
作用机制 Poseltinib may covalently bind to the active site (cysteine 481 residue) of BTK.
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.13mL

0.43mL

0.21mL

10.63mL

2.13mL

1.06mL

21.25mL

4.25mL

2.13mL

参考文献

[1]NCT03099148

[2]NCT02628028

[3]Caldwell RD, Qiu H, Askew BC, Bender AT, Brugger N, Camps M, Dhanabal M, Dutt V, Eichhorn T, Gardberg AS, Goutopoulos A, Grenningloh R, Head J, Healey B, Hodous BL, Huck BR, Johnson TL, Jones C, Jones RC, Mochalkin I, Morandi F, Nguyen N, Meyring M, Potnick JR, Santos DC, Schmidt R, Sherer B, Shutes A, Urbahns K, Follis AV, Wegener AA, Zimmerli SC, Liu-Bujalski L. Discovery of Evobrutinib: An Oral, Potent, and Highly Selective, Covalent Bruton's Tyrosine Kinase (BTK) Inhibitor for the Treatment of Immunological Diseases. J Med Chem. 2019 Sep 12;62(17):7643-7655. doi: 10.1021/acs.jmedchem.9b00794. Epub 2019 Aug 15. PMID: 31368705.

[4]Kim YY, Park KT, Jang SY, Lee KH, Byun JY, Suh KH, Lee YM, Kim YH, Hwang KW. 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. PMID: 28950886; PMCID: PMC5615432.