C646

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: C646
• 英文别名: 4-[(4E)-4-[[5-(4,5-dimethyl-2-nitrophenyl)furan-2-yl]methylidene]-3-methyl-5-oxopyrazol-1-yl]benzoic acid
• 化学式: C24H19N3O6
• 分子量: 445.4
• InChiKey: HEKJYZZSCQBJGB-XDHOZWIPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  129
• 氢给体数：
  1
• 氢受体数：
  7

文献信息

• USE OF HISTONE ACETYLTRANSFERASE INHIBITORS AS NOVEL ANTI-CANCER THERAPIES
  申请人：Alani Rhoda Myra

  公开号：US20130142887A1

  公开（公告）日：2013-06-06

  The present invention provides methods for treating cancer comprising inhibiting the activity of p300/CBP histone acetyltransferase (HAT). Also provided are p300/CBP HAT inhibitors for treating a subject having cancer. In addition, the present invention includes biomarkers for p300/CBP HAT inhibition, which are used to i) monitor the effectiveness of cancer therapy, and ii) identify anti-cancer agents for use in combination therapy.

  本发明提供了用于治疗癌症的方法，包括抑制p300/CBP组蛋白乙酰转移酶（HAT）的活性。同时，本发明还提供了用于治疗患有癌症的受试者的p300/CBP HAT抑制剂。此外，本发明包括用于p300/CBP HAT抑制的生物标志物，用于i）监测癌症治疗的有效性，和ii）识别用于联合治疗的抗癌剂。
• SUBSTITUTED 4-AMINOISOINDOLINE-1,3-DIONE COMPOUNDS AND SECOND ACTIVE AGENTS FOR COMBINED USE
  申请人：Celgene Corporation

  公开号：US20210113576A1

  公开（公告）日：2021-04-22

  Provided herein are methods of using (S)-2-(2,6-dioxopiperidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-1-yl)methyl)benzyl)amino)isoindoline-1,3-dione, or an enantiomer, mixture of enantiomers, tautomer, isotopolog, or pharmaceutically acceptable salt thereof, in combination with a second active agent for treating, preventing or managing hematological malignancies. The second active agent is one or more of an HDAC inhibitor, a BCL2 inhibitor, a BTK inhibitor, an mTOR inhibitor, a PI3K inhibitor, a PKCβ inhibitor, a SYK inhibitor, a JAK2 inhibitor, an Aurora kinase inhibitor, an EZH2 inhibitor, a BET inhibitor, a hypomethylating agent, a DOT1L inhibitor, a HAT inhibitor, a WDR5 inhibitor, a DNMT1 inhibitor, an LSD-1 inhibitor, a G9A inhibitor, a PRMT5 inhibitor, a BRD inhibitor, a SUV420H1/H2 inhibitor, a CARM1 inhibitor, a PLK1 inhibitor, an NEK2 inhibitor, an MEK inhibitor, a PHF19 inhibitor, a PIM inhibitor, an IGF-1R inhibitor, an XPO1 inhibitor, a BIRC5 inhibitor, or a chemotherapy.

  本文提供了使用(S)-2-(2,6-二酮哌啶-3-基)-4-((2-氟-4-((3-吗啡基氮杂环丙烷-1-基)甲基)苯甲基)氨基)异吲哚啉-1,3-二酮或其对映体、对映体混合物、互变异构体、同位素拓扑异构体或其药学上可接受的盐，与第二种活性剂联合治疗、预防或管理血液恶性肿瘤的方法。第二种活性剂是HDAC抑制剂、BCL2抑制剂、BTK抑制剂、mTOR抑制剂、PI3K抑制剂、PKCβ抑制剂、SYK抑制剂、JAK2抑制剂、极化分裂素激酶抑制剂、EZH2抑制剂、BET抑制剂、去甲基化剂、DOT1L抑制剂、HAT抑制剂、WDR5抑制剂、DNMT1抑制剂、LSD-1抑制剂、G9A抑制剂、PRMT5抑制剂、BRD抑制剂、SUV420H1/H2抑制剂、CARM1抑制剂、PLK1抑制剂、NEK2抑制剂、MEK抑制剂、PHF19抑制剂、PIM抑制剂、IGF-1R抑制剂、XPO1抑制剂、BIRC5抑制剂或化疗药物之一。
• METHODS FOR TREATING A HEMATOLOGICAL CANCER AND THE USE OF COMPANION BIOMARKERS FOR 2-(2,6-DIOXOPIPERIDIN-3-YL)-4-((2-FLUORO-4-((3-MORPHOLINOAZETIDIN-1-YL)METHYL)BENZYL)AMINO)ISOINDOLINE-1,3-DIONE
  申请人：CELGENE CORPORATION

  公开号：US20210116454A1

  公开（公告）日：2021-04-22

  A method of identifying a subject having a hematological cancer who is likely to be responsive to a treatment compound, comprising administering the treatment compound to the subject having the hematological cancer; obtaining a sample from the subject; determining the level of a biomarker in the sample from the subject; and diagnosing the subject as being likely to be responsive to the treatment compound if the level of the biomarker in the sample of the subject changes as compared to a reference level of the biomarker; wherein the treatment compound is Compound 1, Compound 2, or Compound 3.

  一种识别可能对治疗化合物有反应的血液肿瘤患者的方法，包括给患有血液肿瘤的受试者注射治疗化合物，从受试者获取样本，测定样本中生物标志物的水平，并在与生物标志物的参考水平相比，如果受试者样本中生物标志物的水平发生变化，则诊断受试者可能对治疗化合物有反应；其中，治疗化合物是化合物1、化合物2或化合物3。
• Reducing systemic regulatory T cell levels or activity for treatment of disease and injury of the CNS
  申请人：Yeda Research and Development Co. Ltd

  公开号：US10144778B2

  公开（公告）日：2018-12-04

  A pharmaceutical composition comprising an active agent that causes reduction of the level of systemic immunosuppression in an individual for use in treating a disease, disorder, condition or injury of the CNS that does not include the autoimmune neuroinflammatory disease, relapsing-remitting multiple sclerosis (RRMS), is provided. The pharmaceutical composition is for administration by a dosage regimen comprising at least two courses of therapy, each course of therapy comprising in sequence a treatment session followed by an interval session.

  本发明提供了一种药物组合物，该药物组合物包含一种活性剂，可降低个体的全身免疫抑制水平，用于治疗中枢神经系统的疾病、失调、状况或损伤，但不包括自身免疫性神经炎症疾病--复发性多发性硬化症（RRMS）。该药物组合物通过至少两个疗程的剂量方案给药，每个疗程依次包括一个治疗疗程和一个间歇疗程。
• Methods for diagnosing and treating cancer by means of the expression status and mutational status of NRF2 and downstream target genes of said gene
  申请人：Genentech, Inc.

  公开号：US11066709B2

  公开（公告）日：2021-07-20

  The invention provides methods of identifying a subject having cancer, such as lung cancer, by analyzing expression levels of one or more NRF2 splice variants or NRF2 target genes. The invention also provides methods of treating cancer in a subject with a NRF2 pathway antagonist, wherein the subject expresses one or more NRF2 splice variants or overexpresses one or more NRF2 target genes.

  本发明提供了通过分析一种或多种NRF2剪接变体或NRF2靶基因的表达水平来鉴定癌症（如肺癌）受试者的方法。本发明还提供了用NRF2通路拮抗剂治疗受试者癌症的方法，其中受试者表达一种或多种NRF2剪接变体或过度表达一种或多种NRF2靶基因。