公开(公告)号：US20140080844A1

公开(公告)日：2014-03-20

申请号：US14085722

申请日：2013-11-20

Applicant: Pharmacyclics, Inc.

Inventor： Wei CHEN ,  David J. LOURY ,  Tarak D. MODY ,  Erik VERNER ,  Mark Stephen SMYTH ,  Wenchen LUO

IPC: C07D487/04

CPC classification number: C07D487/04 ,  C07D519/00

Abstract: Described herein are kinase inhibitor compounds, methods for synthesizing such inhibitors, and methods for using such inhibitors in the treatment of diseases. Further described herein are methods, assays and systems for determining an appropriate inhibitor of a protein, including a kinase.

Abstract translation: 本文描述的是激酶抑制剂化合物，用于合成这种抑制剂的方法，以及在治疗疾病中使用这些抑制剂的方法。 本文进一步描述了用于测定包括激酶在内的蛋白质的适当抑制剂的方法，测定和系统。

公开(公告)号：US20130225812A1

公开(公告)日：2013-08-29

申请号：US13856380

申请日：2013-04-03

Applicant: Pharmacyclics, Inc.

Inventor： Zhengying Pan ,  Shyr Jiann Li ,  Heleen Scheerens ,  Lee Honigberg ,  Erik Verner

IPC: C07D487/04

CPC classification number: C07D487/04 ,  G01N33/573 ,  G01N2333/9121 ,  G01N2500/00

Abstract: Described herein are probes for Bruton's tyrosine kinase (Btk). Such probes are used to characterize and develop Btk-selective inhibitors intended for therapeutic use.

Abstract translation: 本文描述的是布鲁顿酪氨酸激酶（Btk）的探针。 这种探针用于表征和开发用于治疗用途的Btk选择性抑制剂。

公开(公告)号：WO2015143400A1

公开(公告)日：2015-09-24

申请号：PCT/US2015/021871

申请日：2015-03-20

Applicant: PHARMACYCLICS, INC.

Inventor： BYRD, John, C. ,  WOYACH, Jennifer, A.

IPC: C12Q1/68

CPC classification number: C12Q1/6886 ,  A61K31/519 ,  C12Q2600/106 ,  C12Q2600/156 ,  G01N33/57426 ,  G01N2333/916 ,  G01N2800/52

Abstract: Described herein is a mutation that confers resistance to the treatment with a BTK inhibitor. Described herein is a modified PLCy2 polypeptide that is modified at amino acid position 742, 845, or 1140 and the modified PLCy2 polypeptide exhibits decreased inhibition (e.g., resistance) to a covalent and/or irreversible BTK inhibitor. Described herein are diagnostic methods for detecting the modified polypeptide and nucleic acid encoding the modified polypeptide and applications of the methods thereof. Described herein are compositions, combinations, and kits containing the modified polypeptide and methods of using the modified polypeptide. Also described herein are methods of using the modified polypeptide as screening agents for the identification and design of inhibitors of PLCy2.

Abstract translation: 本文描述了赋予对用BTK抑制剂治疗的抗性的突变。 本文描述的是在氨基酸位置742,845或1140修饰的修饰的PLCy2多肽，并且修饰的PLCy2多肽对共价和/或不可逆的BTK抑制剂表现出降低的抑制（例如抗性）。 本文描述了用于检测修饰的多肽和编码经修饰的多肽的核酸的诊断方法及其方法的应用。 本文描述的是含有修饰多肽的组合物，组合和试剂盒，以及使用修饰多肽的方法。 本文还描述了使用修饰的多肽作为用于鉴定和设计PLCy2的抑制剂的筛选剂的方法。

公开(公告)号：WO2015023703A1

公开(公告)日：2015-02-19

申请号：PCT/US2014/050783

申请日：2014-08-12

Applicant: PHARMACYCLICS, INC. ,  CHEN, Jun ,  BUGGY, Joseph, J. ,  ELIAS, Laurence

Inventor： CHEN, Jun ,  BUGGY, Joseph, J. ,  ELIAS, Laurence

IPC: A61K31/4162 ,  A61K31/4155 ,  A61K31/519 ,  A61K31/506 ,  A61P35/00

CPC classification number: A61K31/519 ,  A61K31/454 ,  A61K45/06

Abstract: Described herein are methods and compositions for treating HER2-amplified cancer. The methods include administering to an individual in need thereof ibrutinib.

Abstract translation: 本文描述了用于治疗HER2扩增的癌症的方法和组合物。 所述方法包括向有需要的个体施用伊布他尼。

公开(公告)号：WO2014168975A1

公开(公告)日：2014-10-16

申请号：PCT/US2014/033378

申请日：2014-04-08

Applicant: PHARMACYCLICS, INC. ,  JANSSEN PHARMACEUTICA NV ,  CHANG, Betty ,  BALASUBRAMANIAN, Sriram ,  CROWLEY, Richard ,  KUO, Hsu-Ping

Inventor： CHANG, Betty ,  BALASUBRAMANIAN, Sriram ,  CROWLEY, Richard ,  KUO, Hsu-Ping ,  HALL, Brett ,  SASSER, A. Kate ,  SCHAFFER, Michael ,  DAVIS, Cuc ,  CASNEUF, Tineke ,  VERSELE, Matthias ,  LIGTENBERG, Willem

IPC: A61K31/519 ,  A61K31/573 ,  A61K31/56 ,  A61P35/00

CPC classification number: A61K31/519 ,  A61K31/282 ,  A61K31/395 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/4745 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/5383 ,  A61K31/573 ,  A61K31/664 ,  A61K31/704 ,  A61K31/7048 ,  A61K31/7068 ,  A61K39/3955 ,  A61K45/06 ,  A61K2039/505 ,  A61K2300/00

Abstract: Combinations of Bruton's tyrosine kinase (Btk) inhibitors, e.g., 1-((R)-3-(4-amino-phenoxyphenyl)- 1 H-pyrazolo [3,4-d]pyrimidin- 1 -yl)piperidin- 1 -yl)prop-2-en- 1 -one, with a second anticancer agent are provided. Also provided are methods of treating cancers, and autoimmune disorders by administering combinations of Bruton's tyrosine kinase (Btk) inhibitors, e.g., 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1- yl)piperidin-1-yl)prop-2-en-1-one, and second anticancer agents.

Abstract translation: Bruton酪氨酸激酶（Btk）抑制剂的组合，例如1 - （（R）-3-（4-氨基 - 苯氧基苯基）-1H-吡唑并[3,4-d]嘧啶-1-基）哌啶-1-基] 哌嗪-1-基）丙-2-烯-1-酮与第二抗癌剂。 还提供了通过施用布鲁顿酪氨酸激酶（Btk）抑制剂的组合来治疗癌症和自身免疫性疾病的方法，例如1 - （（R）-3-（4-氨基-3-（4-苯氧基苯基）-1H-吡唑并 [3,4-d]嘧啶-1-基）哌啶-1-基）丙-2-烯-1-酮和第二抗癌剂。

公开(公告)号：WO2014071231A1

公开(公告)日：2014-05-08

申请号：PCT/US2013/068132

申请日：2013-11-01

Applicant: PHARMACYCLICS, INC. ,  BUGGY, Joseph, J. ,  MODY, Tarak ,  LOVE, Richard, B. ,  BYRD, John, C. ,  CHANG, Betty

Inventor： BUGGY, Joseph, J. ,  MODY, Tarak ,  LOVE, Richard, B. ,  BYRD, John, C. ,  CHANG, Betty

IPC: A61K31/505 ,  A61K38/20 ,  A61P35/00

CPC classification number: A61K31/519 ,  A61K45/06 ,  A61K2300/00

Abstract: Described herein are methods and compositions comprising a covalent TEC family kinase inhibitor for use in adjuvant therapy, including adjuvant cancer therapy, vaccination and treatment of immune disorders and pathogenic infections.

Abstract translation: 本文描述了包含用于辅助治疗的共价TEC家族激酶抑制剂的方法和组合物，包括佐剂癌症治疗，疫苗接种和治疗免疫疾病和致病性感染。

公开(公告)号：WO2013039488A1

公开(公告)日：2013-03-21

申请号：PCT/US2011/051470

申请日：2011-09-13

Applicant: PHARMACYCLICS, INC. ,  LOURY, David, J. ,  BUGGY, Joseph, J. ,  MODY, Tarak, D. ,  VERNER, Erik, J. ,  PURRO, Norbert ,  BALASUBRAMANIAN, Sriram ,  KLOOS, Ioana ,  DEPIL, Stéphane ,  LES LABORATOIRES SERVIER SAS

Inventor： LOURY, David, J. ,  BUGGY, Joseph, J. ,  MODY, Tarak, D. ,  VERNER, Erik, J. ,  PURRO, Norbert ,  BALASUBRAMANIAN, Sriram ,  KLOOS, Ioana ,  DEPIL, Stéphane

IPC: A61K31/343 ,  A61K31/166 ,  A61K31/16 ,  A61P35/00

CPC classification number: A61K31/343 ,  A61K9/14 ,  A61K9/28 ,  A61K9/70 ,  A61K31/4184 ,  A61K2300/00

Abstract: Dosing regimens, methods of treatment, controlled release formulations, and combination therapies that include bendamustine, or a pharmaceutically acceptable salt thereof and an HDAC inhibitor, or a pharmaceutically acceptable salt thereof, are described.

Abstract translation: 描述了给药方案，治疗方法，控制释放制剂和包括苯达莫司汀或其药学上可接受的盐和HDAC抑制剂或其药学上可接受的盐的组合疗法。

公开(公告)号：WO2013003629A2

公开(公告)日：2013-01-03

申请号：PCT/US2012/044708

申请日：2012-06-28

Applicant: PHARMACYCLICS, INC. ,  BUGGY, Joseph J. ,  CHANG, Betty Y.

Inventor： BUGGY, Joseph J. ,  CHANG, Betty Y.

CPC classification number: C07D487/04 ,  A61K9/0014 ,  A61K9/0019 ,  A61K9/0031 ,  A61K9/0048 ,  A61K9/0056 ,  A61K9/0078 ,  A61K31/00 ,  A61K31/519

Abstract: Disclosed herein are methods and compounds for inhibiting bone and/or cartilage resorption in an individual. The methods comprise administering to the individual a composition comprising a therapeutically effective amount of a compound that is an irreversible inhibitor of a Bruton's tyrosine kinase (BTK), or a pharmaceutically acceptable salt thereof. Also described are irreversible inhibitors of Btk and methods for the preparation of the compounds. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are disclosed, alone or in combination with other therapeutic agents, for the inhibition of cancer metastasis, and for inhibition of bone or cartilage resorption in cancer patients.

Abstract translation: 本文公开了用于抑制个体中骨和/或软骨吸收的方法和化合物。 所述方法包括向个体施用包含治疗有效量的作为Bruton酪氨酸激酶（BTK）的不可逆抑制剂的化合物或其药学上可接受的盐的组合物。 还描述了Btk的不可逆抑制剂和制备化合物的方法。 还公开了包含化合物的药物组合物。 公开了单独使用Btk抑制剂的方法或与其它治疗剂组合用于抑制癌症转移以及抑制癌症患者中的骨或软骨吸收。

公开(公告)号：WO2011046964A3

公开(公告)日：2011-08-25

申请号：PCT/US2010052377

申请日：2010-10-12

Applicant: PHARMACYCLICS INC ,  CHEN WEI ,  LOURY DAVID J ,  MODY TARAK D ,  VERNER ERIK ,  SMYTH MARK STEPHEN ,  LUO WENCHEN

Inventor： CHEN WEI ,  LOURY DAVID J ,  MODY TARAK D ,  VERNER ERIK ,  SMYTH MARK STEPHEN ,  LUO WENCHEN

IPC: C07D487/04 ,  A61K31/519 ,  A61P19/02 ,  A61P19/10 ,  C07D401/04 ,  C07D401/14

CPC classification number: C07D487/04 ,  C07D519/00

Abstract: Described herein are kinase inhibitor compounds, methods for synthesizing such inhibitors, and methods for using such inhibitors in the treatment of diseases. Further described herein are methods, assays and systems for determining an appropriate inhibitor of a protein, including a kinase.

Abstract translation: 本文描述的是激酶抑制剂化合物，用于合成这种抑制剂的方法，以及在治疗疾病中使用这些抑制剂的方法。 本文进一步描述了用于测定包括激酶在内的蛋白质的适当抑制剂的方法，测定和系统。

公开(公告)号：WO2009129335A3

公开(公告)日：2009-10-22

申请号：PCT/US2009/040709

申请日：2009-04-15

Applicant: PHARMACYCLICS, INC. ,  VERNER, Erik ,  BALASUBRAMANIAN, Sriram ,  BUGGY, Joseph, J.

Inventor： VERNER, Erik ,  BALASUBRAMANIAN, Sriram ,  BUGGY, Joseph, J.

IPC: C07D235/06 ,  C07D235/08 ,  C07D235/10 ,  C07D235/12 ,  C07D235/14

Abstract: Described herein are compounds and pharmaceutical compositions containing such compounds, which inhibit the acitivy of histone deacetylase 8 (HDAC8). Also described herein are methods of using such HDAC8 inhibitors, alone and in combination with other compounds, for treating diseases or conditions that would benefit from inhibition of HDAC8 activity.