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    Inhibidores de la tirosina quinasa de Bruton
    5.
    发明专利
    Inhibidores de la tirosina quinasa de Bruton 未知

    公开(公告)号：ES2562215T3

    公开(公告)日：2016-03-03

    申请号：ES08744513

    申请日：2008-03-27

    Applicant: PHARMACYCLICS LLC

    Inventor： HONIGBERG LEE ,  VERNER ERIK ,  BUGGY JOSEPH J ,  LOURY DAVID ,  CHEN WEI

    IPC: A61K31/52 ,  A61K31/519 ,  A61P29/00 ,  A61P35/00 ,  C07D253/06 ,  C07D473/34 ,  C07D487/04

    Abstract: Un compuesto de Fórmula (I),**Fórmula** en la que: La es O; Ar es fenilo; Y es alquilenheterocicloalquileno; Z es C(>=O), NHC(>=O), NRaC(>=O), o NRaS(>=O)x, 10 en el que x es 1 ó 2, y Ra es H, alquilo sustituido o no sustituido, cicloalquilo sustituido o no sustituido; y: R6 y R8 son H; y R7 es H, alquiloC1-C4 sustituido o no sustituido, heteroalquiloC1-C4 sustituido o no sustituido, alquilaminoalquiloC1-C8, hidroxialquilaminoalquiloC1-C8, alcoxialquilaminoalquiloC1-C8, cicloalquiloC3-C6 sustituido o no sustituido, alquilC1- C8cicloalquiloC3-C6 sustituido o no sustituido, arilo sustituido o no sustituido, heteroarilo sustituido o no sustituido, alquilC1-C4(arilo), alquilC1-C4(heteroarilo), heterocicloalquiloC2-C8sustituido o no sustituido, alquiléteresC1-C8, alquilamidasC1-C8, o alquilC1-C4(heterocicloalquiloC2-C8); o una sal farmacéuticamente aceptable de éste.

    Methods for determining cancer resistance to histone deacetylase inhibitors
    8.
    发明专利
    Methods for determining cancer resistance to histone deacetylase inhibitors 未知

    公开(公告)号：AU2008210421B2

    公开(公告)日：2014-03-13

    申请号：AU2008210421

    申请日：2008-01-30

    Applicant: PHARMACYCLICS LLC

    Inventor： BALASUBRAMANIAN SRIRAM ,  BUGGY JOSEPH J

    IPC: A61K49/00 ,  C12Q1/68 ,  G01N33/574

    Abstract: [00153] Described herein are methods and compositions for determining whether a particular cancer is resistant to or susceptible to a histone deacetylase inhibitor or to histone deacetylase inhibitors. The methods include analysis of the expression levels of at least four biomarker genes associated with response to a histone deacetylase inhibitor. Also described herein are methods and compositions for increasing the likelihood of a therapeutically effective treatment in a patient, comprising an analysis of the expression levels of at least four biomarker genes associated with response to a histone deacetylase inhibitor. Also described herein are isolated populations of nucleic acids derived from a cancer sensitive to or resistant to a histone deacetylase inhibitor. Further described are kits and indications that are used in conjunction with the aforementioned methods and compositions.

    Inhibitors of Bruton's tyrosine kinase
    9.
    发明专利
    Inhibitors of Bruton's tyrosine kinase 未知

    公开(公告)号：AU2013276959A1

    公开(公告)日：2014-01-16

    申请号：AU2013276959

    申请日：2013-12-19

    Applicant: PHARMACYCLICS LLC

    Inventor： HONIGBERG LEE ,  VERNER ERIK ,  BUGGY JOSEPH J ,  LOURY DAVID ,  CHEN WEI

    IPC: C07D253/06 ,  A61K31/519 ,  A61K31/52 ,  A61P29/00 ,  A61P35/00 ,  C07D473/34 ,  C07D487/04

    Abstract: INHIBITORS OF BRUTON'S TYROSINE KINASE 1005171 Described herein are irreversible kinase inhibitor compounds, methods for synthesizing such irreversible inhibitors, and methods for using such irreversible inhibitors in the treatment of diseases. Further 5 described herein are methods, assays and systems for determining an appropriate irreversible inhibitor of a protein, including a kinase. S Cmpd Cell line Gl5 (uM) WSU-NHL 0.12 Mino 0.15 WSU-DLCL2 0.5 Ramos 5.5 HF1 >10 LY19 >10 LY3 >10 :DB >10 DLCL2 Xenograft -o-vehicle 400 -- ~Cmpd 1 10mg/kg -U- Cmpd 1 30mg/kg 300 --+- Cmpd 1 90mg/kg 2 300 -.... - - -.... . ..... 0 3 6 9 12 15 18 Day DOHH2 Xenograft -c-vehicle 700 --- m- Cmpd 1 25mg/kg BID 500 ........ .......... E 300 - - - -- - 100 or 0 5 Day 10 15 Figure 1

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