- A PYRAZOLOPYRIMIDINE DERIVATIVE AS A HCK INHIBITOR FOR USE IN THERAPY, IN PARTICULAR MYD88 MUTATED DISEASES
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Provided herein are methods of treating diseases (e.g., proliferative disease (e.g., cancer (e.g., breast cancer, colon cancer, testicular cancer, CNS cancer, stomach cancer, lymphoma (e.g., B-cell lymphoma (e.g., lymphoplasmacytic lymphoma (e.g., IgM secreting lymphoplasmacytic lymphoma (i.e., Waldenstrom's Macroglobulinemia), non-IgM secreting lymphoplasmacytic lymphoma)), diffuse large B-cell lymphoma (e.g., activated B -cell-like (ABC)- DLBCL, germinal center B -cell-like (GBC)-DLBCL), follicular lymphoma, marginal zone B-cell lymphoma, small lymphocytic lymphoma, mantle cell lymphoma), and leukemia (e.g., chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia, myelogenous leukemia (e.g., chronic myelogenous leukemia, acute myelogenous leukemia))))) comprising administering to the subject in need thereof a therapeutically effective amount of Compound (I). Further provided are methods for treating disease resistant to treatment with BTK inhibitors (e.g., ibmtinib). Formula (I)
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Paragraph 00228; 00230
(2021/04/17)
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- HCK DEGRADERS AND USES THEREOF
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Provided herein are bifunctional compounds with a moiety (e.g., lenalidomide, thalidomide) that is a binder of an E3 ubiquitin ligase (e.g., Cereblon) and another moiety that is a binder of a kinase (e.g., HCK, BTK) to induce degradation of the kinase (e.g., HCK, BTK). Also provided are pharmaceutical compositions comprising the bifunctional compounds, and methods of treating and/or preventing diseases (e.g., proliferative diseases (e.g., non-Hodgkin's lymphoma, Burkitt's lymphoma, Waldenstrom macroglobulinemia, MYD88-mutated Waldenstrom macroglobulinemia, activated B-cell diffuse large B-cell lymphoma, leukemia)), inflammatory disease, or other diseases associated with MYD88 mutations). Provided also are methods of inducing the degradation of a kinase (e.g., HCK, BTK) in a cell in a biological sample or subject by administering the bifunctional compound or composition described herein.
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Paragraph 00350
(2021/01/23)
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- Cyclohexane derivatives difunctionalised in 1,4 as ligands of 5T H1A receptors
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The invention concerns novel cyclohexane derivatives difunctionalised in 1.4 of general formula (1) in which A represents a group such as (IIa) in which Ar itself represents an aromatic structure such as phenyl or pyrimidinyl optionally substituted by one
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