Branched chain amino acids

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Branched chain amino acids
• 英文别名: 2-amino-3-methylbutanoic acid;2-amino-3-methylpentanoic acid;2-amino-4-methylpentanoic acid
• 化学式: C17H37N3O6
• 分子量: 379.5
• InChiKey: OCUSNPIJIZCRSZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.94
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  190
• 氢给体数：
  6
• 氢受体数：
  9

文献信息

• [EN] METHOD OF TREATING LUNG ADENOCARCINOMA<br/>[FR] PROCÉDÉ DE TRAITEMENT DE L'ADÉNOCARCINOME DU POUMON
  申请人：EXELIXIS INC

  公开号：WO2015164869A1

  公开（公告）日：2015-10-29

  This invention is directed to the treatment of cancer in a patient, particularly a patient with lung adenocarcinoma, and more particularly a patient with SLC34A2-ROS1, CD74-ROS1, or FIG-ROSl fusion-positive non-small cell lung cancer, with an inhibitor of MET, VEGFR2, and ROS1 which is a compound of Formula (I): or a pharmaceutically acceptable salt thereof.

  本发明涉及治疗癌症患者，特别是肺腺癌患者，更特别是患有SLC34A2-ROS1、CD74-ROS1或FIG-ROS1融合阳性非小细胞肺癌的患者，使用MET、VEGFR2和ROS1的抑制剂，该抑制剂为化合物(I)的一种，或其药用可接受盐。
• Gene defects and mutant ALK kinase in human solid tumors
  申请人：Cell Signaling Technology, Inc.

  公开号：EP2447359A1

  公开（公告）日：2012-05-02

  In accordance with the invention, novel gene deletions and translocations involving chromosome 2 resulting in fusion proteins combining part of Anaplastic Lymphoma Kinase (ALK) kinase with part of a secondary protein have now been identified in human solid tumors, e.g. non-small cell lung carcinoma (NSCLC). Secondary proteins include Echinoderm Microtubule-Associated Protein-Like 4 (EML-4) and TRK-Fusion Gene (TFG). The EML4-ALK fusion protein, which retains ALK tyrosine kinase activity, was confirmed to drive the proliferation and survival of NSCLC characterized by this mutation. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ALK kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of this new fusion protein enables new methods for determining the presence of these mutant ALK kinase polypeptides in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.

  根据本发明，目前已在人类实体瘤（如非小细胞肺癌（NSCLC））中发现了涉及 2 号染色体的新型基因缺失和易位，这些基因缺失和易位产生的融合蛋白结合了部分无性淋巴瘤激酶（ALK）激酶和部分次级蛋白。次级蛋白包括棘皮动物微管相关蛋白（Echinoderm Microtubule-Associated Protein-Like 4，EML-4）和TRK融合基因（TRK-Fusion Gene，TFG）。EML4-ALK融合蛋白保留了ALK酪氨酸激酶的活性，已被证实能驱动以这种突变为特征的NSCLC的增殖和存活。因此，本发明部分提供了编码所公开的突变 ALK 激酶多肽的分离多核苷酸和载体、检测其的探针、分离的突变多肽、重组多肽以及检测融合多肽和截短多肽的试剂。本发明所公开的这种新的融合蛋白的鉴定，使得确定生物样本中是否存在这些突变ALK激酶多肽的新方法、筛选抑制这些蛋白的化合物的方法以及抑制以突变多核苷酸或多肽为特征的癌症进展的方法成为可能。
• Translocation and mutant ROS kinase in human non-small cell lung carcinoma
  申请人：Cell Signaling Technology, Inc.

  公开号：EP2671954A2

  公开（公告）日：2013-12-11

  In accordance with the invention, a novel gene translocation, (4p15, 6q22), in human non-small cell lung carcinoma (NSCLC) that results in a fusion proteins combining part of Sodium-dependent Phosphate Transporter Isoform NaPi-3b protein (SLC34A2) with Proto- oncogene Tyrosine Protein Kinase ROS Precursor (ROS) kinase has now been identified. The SLC34A2-ROS fusion protein is anticipated to drive the proliferation and survival of a subgroup of NSCLC tumors. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ROS kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of the new fusion protein enables new methods for determining the presence of these mutant ROS kinase polypeptides in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.

  根据本发明，在人类非小细胞肺癌（NSCLC）中发现了一种新的基因易位（4p15，6q22），这种易位导致了一种融合蛋白，它结合了部分依赖钠的磷酸盐转运体异构体 NaPi-3b 蛋白（SLC34A2）和原癌基因酪氨酸蛋白激酶 ROS 前体（ROS）激酶。预计 SLC34A2-ROS 融合蛋白将推动 NSCLC 肿瘤亚群的增殖和存活。因此，本发明部分提供了编码所公开的突变 ROS 激酶多肽的分离多核苷酸和载体、用于检测它的探针、分离的突变多肽、重组多肽以及用于检测融合多肽和截短多肽的试剂。本发明还提供了用于确定生物样本中是否存在这些突变 ROS 激酶多肽的新方法、用于筛选抑制这些蛋白质的化合物的方法以及用于抑制以突变多核苷酸或多肽为特征的癌症进展的方法。
• METHOD FOR DETECTING A FIG-ROS FUSION POLYNUCLEOTIDE
  申请人：Cell Signaling Technology, Inc.

  公开号：EP3266795A1

  公开（公告）日：2018-01-10

  The present application provides methods for detecting a FIG-ROS fusion polynucleotide in a biological sample from a subject having liver cancer. In some embodiments, the FIG-ROS fusion proteins comprise part of the FIG protein fused to the kinase domain of the ROS kinase.

  本申请提供了在肝癌患者的生物样本中检测 FIG-ROS 融合多核苷酸的方法。在某些实施方案中，FIG-ROS 融合蛋白包括与 ROS 激酶的激酶结构域融合的部分 FIG 蛋白。
• INNATE IMMUNE SUPRESSION ENABLES REPEATED DELIVERY OF LONG RNA MOLECULES
  申请人：Massachusetts Institute Of Technology

  公开号：EP3524275A1

  公开（公告）日：2019-08-14

  Disclosed are methods for suppressing the innate immune response of a cell to transfection with an exogenous nucleic acid. Further disclosed are methods for increasing expression of a protein encoded by an exogenous nucleic acid by repeated delivery of the exogenous nucleic acid to a cell, and methods of changing the phenotype of a cell by differentiating, transdifferentiating or dedifferentiating cells by repeatedly delivering one or more nucleic acids that encode defined proteins. A method is provided for extended transient transfection by repeated delivery of an in vitro-transcribed RNA ("ivT-RNA) to a cell to achieve a high and sustained level of expression of a protein encoded by an ivT-RNA transcripts.

  公开了抑制细胞对外源核酸转染的先天免疫反应的方法。还公开了通过重复向细胞递送外源核酸来增加外源核酸编码的蛋白质表达的方法，以及通过重复递送一种或多种编码确定蛋白质的核酸来分化、转分化或去分化细胞从而改变细胞表型的方法。本发明提供了一种通过向细胞重复递送体外转录 RNA（"ivT-RNA"）来延长瞬时转染的方法，以实现由 ivT-RNA 转录本编码的蛋白质的高水平持续表达。