940890-90-4Relevant articles and documents
Tumor-Cell-Specific Targeting of Ibrutinib: Introducing Electrostatic Antibody-Inhibitor Conjugates (AiCs)
B?umer, Nicole,B?umer, Sebastian,Becht, Manuel,Berdel, Wolfgang E.,Dersch, Petra,Faust, Andreas,Geyer, Christiane,Greune, Lilo,Lenz, Georg,Margeta, Renato,Rüter, Christian,Schlütermann, Alina,Wittmann, Lisa
supporting information, (2021/12/09)
Ibrutinib is an inhibitor of Bruton's tyrosine kinase that has been approved for the treatment of patients with chronic lymphocytic leukemia, mantle cell lymphoma and Waldenstrom's macroglobulinemia and is connected with toxicities. To minimize its toxicities, we linked ibrutinib to a cell-targeted, internalizing antibody. To this end, we synthesized a poly-anionic derivate, ibrutinib-Cy3.5, that retains full functionality. This anionic inhibitor is complexed by our anti-CD20-protamine targeting conjugate and free protamine, and thereby spontaneously assembles into an electrostatically stabilized vesicular nanocarrier. The complexation led to an accumulation of the drug driven by the CD20 antigen internalization to the intended cells and an amplification of its pharmacological effectivity. In vivo, we observed a significant enrichment of the drug in xenograft lymphoma tumors in immune-compromised mice and a significantly better response to lower doses compared to the original drug.
ANTITUMOR-EFFECT ENHANCER USING PYRAZOLO[3,4-D]PYRIMIDINE COMPOUND
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Paragraph 0286, (2020/01/22)
To provide a method for treating cancer using a pyrazolo[3,4-d]pyrimidine compound or a salt thereof. The present invention provides an antitumor agent comprising a pyrazolo[3,4-d]pyrimidine compound of formula (I) wherein X, Y, Z1, Z2/su
COMPOUNDS
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Page/Page column 183, (2017/02/09)
Disclosed are novel compounds that inhibit LRRK2 kinase activity, processes for their preparation, compositions containing them and their use in the treatment of or prevention of diseases characterized by LRRK2 kinase activity, for example Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis(ALS).