公开(公告)号：US20160106835A1

公开(公告)日：2016-04-21

申请号：US14893746

申请日：2014-05-28

申请人： Axel HOOS ,  Keith W. ORFORD ,  Patrick CHUN ,  Venkatarama SRIRAM ,  Elaine M. PINHEIRO ,  Scot W. EBBINGHAUS ,  GLAXOSMITHKLINE LLC ,  MERCK SHARP & DOHME CORP.

发明人： Axel Hoos ,  Keith W. Orford ,  Patrick Chun ,  Venkataraman Sriram ,  Elaine M. Pinheiro ,  Scot W. Ebbinghaus

IPC分类号： A61K39/395 ,  A61K31/519 ,  A61K31/506

CPC分类号： A61K39/3955 ,  A61K31/506 ,  A61K31/519 ,  A61K2039/505 ,  C07K16/2818 ,  C07K2317/76 ,  A61K2300/00

摘要： A novel combination comprising a B-Raf inhibitor, particularly N-{3-[5-(2-Amino-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide or a pharmaceutically acceptable salt thereof, the MEK inhibitor N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)6,8-dimethyl; -2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide, or a pharmaceutically acceptable salt or solvate thereof, and a PD-1 antagonist; pharmaceutical compositions comprising the same and methods of using such combinations and compositions in the treatment of conditions in which the inhibition of MEK and/or B-Raf and/or immune modulation through PD-1 is beneficial, e.g., cancer.

摘要翻译： 包含B-Raf抑制剂，特别是N- {3- [5-（2-氨基-4-嘧啶基）-2-（1,1-二甲基乙基）-1,3-噻唑-4-基] - 2-氟苯基} -2,6-二氟苯磺酰胺或其药学上可接受的盐，MEK抑制剂N- {3- [3-环丙基-5-（2-氟-4-碘 - 苯基氨基）6,8-二甲基; -2,4,7-三氧代-3,4,6,7-四氢-2H-吡啶并[4,3-d]嘧啶-1-基]苯基}乙酰胺或其药学上可接受的盐或溶剂合物，和 PD-1拮抗剂; 包含其的药物组合物和使用这些组合和组合物治疗MEK和/或B-Raf的抑制和/或通过PD-1的免疫调节有利的条件的方法，例如癌症。

公开(公告)号：US07405041B2

公开(公告)日：2008-07-29

申请号：US10645471

申请日：2003-08-20

申请人： Scot W. Ebbinghaus ,  Laurence H. Hurley ,  Adam Siddiqui-Jain ,  Regan Memmott

发明人： Scot W. Ebbinghaus ,  Laurence H. Hurley ,  Adam Siddiqui-Jain ,  Regan Memmott

IPC分类号： C12Q1/68

CPC分类号： C07D513/22 ,  Y10S977/924

摘要： Among the different intrastrand quadruplex structures that can arise from duplex DNA, it has been discovered that the nucleotide sequences (GGA)4 (SEQ ID NO: 1) and (GGA)3GG (SEQ ID NO: 2) form biologically significant quadruplex structures. Thus, provided herein are methods for identifying molecules that modulate the biological activity of quadruplex DNA comprising the nucleotide sequence (GGA)4 (SEQ ID NO: 1) or the nucleotide sequence (GGA)3GG (SEQ ID NO: 2), and specifically, methods for identifying molecules that bind such quadruplexes. Also provided herein are methods for modulating the biological activity of a biologically significant native quadruplex DNA with a molecule identified by the methods described herein.

摘要翻译： 在双链DNA可能产生的不同的intrastrand四链体结构中，已经发现核苷酸序列（GGA）4（SEQ ID NO：1）和（GGA）3