1418307-23-9Relevant academic research and scientific papers
The compounds of structure containing conjugated zincon, its pharmaceutical composition and use thereof (by machine translation)
-
, (2018/03/24)
The present invention relates to compounds having a structure containing conjugated zincon, its pharmaceutical composition and use, and in particular relates to the general formula (I) or a salt thereof to the compound represented by the, pharmaceutical compositions thereof, and its as BTK inhibitors and/or B cell activation inhibitor, for the prevention or treatment B cell activity with abnormal and/or the use of the BTK-related diseases. The compounds of lymphoma, breast cancer, liver cancer, colon cancer, gastric cancer, such as lung cancer and cervical cancer cell has better lethal effect, note has potential for the treatment of cancer and self-immune diseases related to potential. (by machine translation)
BRUTON'S TYROSINE KINASE INHIBITORS
-
Page/Page column 29-30, (2018/10/19)
Bruton's tyrosine kinase (Btk) inhibitors have the following Formula (I).
COMPOSITIONS AND METHODS FOR THE ASSESSMENT OF DRUG TARGET OCCUPANCY FOR BRUTON'S TYROSINE KINASE
-
Paragraph 00198; 00199, (2018/08/12)
In some embodiments, the invention relates to compositions, methods, and kits for assessment of drug target occupancy in Bruton's tyrosine kinase (BTK) in a selective and sensitive manner for use with BTK inhibitor therapy in the treatment of Bruton's tyrosine kinase (BTK) mediated disorders, including cancers, inflammatory diseases, and immune and autoimmune diseases.
Acalabrutinib (ACP-196): A covalent Bruton tyrosine kinase inhibitor with a differentiated selectivity and in vivo potency profile
Barf, Tjeerd,Covey, Todd,Izumi, Raquel,Van De Kar, Bas,Gulrajani, Michael,Van Lith, Bart,Van Hoek, Maaike,De Zwart, Edwin,Mittag, Diana,Demont, Dennis,Verkaik, Saskia,Krantz, Fanny,Pearson, Paul G.,Ulrich, Roger,Kaptein, Allard
supporting information, p. 240 - 252 (2018/11/23)
Several small-molecule Bruton tyrosine kinase (BTK) inhibitors are in development for B cell malignancies and autoimmune disorders, each characterized by distinct potency and selectivity patterns. Herein we describe the pharmacologic characterization of BTK inhibitor acalabrutinib [compound 1, ACP-196 (4-[8-amino-3-[(2S)-1-but-2-ynoylpyrrolidin-2-yl]imidazo[1,5-a]pyrazin-1-yl]-N-(2-pyridyl)benzamide)]. Acalabrutinib possesses a reactive butynamide group that binds covalently to Cys481 in BTK. Relative to the other BTK inhibitors described here, the reduced intrinsic reactivity of acalabrutinib helps to limit inhibition of off-target kinases having cysteine-mediated covalent binding potential. Acalabrutinib demonstrated higher biochemical and cellular selectivity than ibrutinib and spebrutinib (compounds 2 and 3, respectively). Importantly, off-target kinases, such as epidermal growth factor receptor (EGFR) and interleukin 2-inducible T cell kinase (ITK), were not inhibited. Determination of the inhibitory potential of anti-immunoglobulin M-induced CD69 expression in human peripheral blood mononuclear cells and whole blood demonstrated that acalabrutinib is a potent functional BTK inhibitor. In vivo evaluation in mice revealed that acalabrutinib is more potent than ibrutinib and spebrutinib. Preclinical and clinical studies showed that the level and duration of BTK occupancy correlates with in vivo efficacy. Evaluation of the pharmacokinetic properties of acalabrutinib in healthy adult volunteers demonstrated rapid absorption and fast elimination. In these healthy individuals, a single oral dose of 100 mg showed approximately 99% median target coverage at 3 and 12 hours and around 90% at 24 hours in peripheral B cells. In conclusion, acalabrutinib is a BTK inhibitor with key pharmacologic differentiators versus ibrutinib and spebrutinib and is currently being evaluated in clinical trials.
4-IMIDAZOPYRIDAZIN-1-YL-BENZAMIDES AND 4-IMIDAZOTRIAZIN-1-YL-BENZAMIDES BTK-INHIBITORS
-
, (2013/03/26)
The present invention relates to 6-5 membered fused pyridine ring compounds of formula (I) or a pharmaceutically acceptable salt thereof or to pharmaceutical compositions comprising these compounds and to their use in therapy. In particular, the present invention relates to the use of 6-5 membered fused pyridine ring compounds in the treatment of Bruton's Tyrosine Kinase (Btk) mediated disorders.
