WMY-1-103 | 1209002-43-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: WMY-1-103
• 英文别名: (R)-2-chloro-N-(2-(5-(dimethylamino)naphthalene-1-sulfonamido)ethyl)-4-(2-(1-hydroxy-3-methylbutan-2-ylamino)-9-isopropyl-9H-purin-6-ylamino)benzamide；VMY-1-103；2-chloro-N-[2-[[5-(dimethylamino)naphthalen-1-yl]sulfonylamino]ethyl]-4-[[2-[[(2R)-1-hydroxy-3-methylbutan-2-yl]amino]-9-propan-2-ylpurin-6-yl]amino]benzamide
• CAS: 1209002-43-6
• 化学式: C₃₄H₄₂ClN₉O₄S
• 分子量: 708.284
• InChiKey: NJNQGMFCZFMREY-MHZLTWQESA-N

物化性质

• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  49
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  175
• 氢给体数：
  5
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  2-氟-6-氯嘌呤 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 正丁醇 为溶剂， 反应 108.0h， 生成 WMY-1-103
  参考文献：
  名称：

  Fluorescent cyclin-dependent kinase inhibitors block the proliferation of human breast cancer cells

  摘要：

  Inhibitors of cyclin-dependent kinases (CDKs) are an emerging class of drugs for the treatment of cancers. CDK inhibitors are currently under evaluation in clinical trials as single agents and as sensitizers in combination with radiation therapy and chemotherapies. Drugs that target CDKs could have important inhibitory effects on cancer cell cycle progression, an extremely important mechanism in the control of cancer cell growth. Using rational drug design, we designed and synthesized fluorescent CDK inhibitors (VMY-1-101 and VMY-1-103) based on a purvalanol B scaffold. The new agents demonstrated more potent CDK inhibitory activity, enhanced induction of G2/M arrest and modest apoptosis as compared to purvalanol B. Intracellular imaging of the CDK inhibitor distribution was performed to reveal drug retention in the cytoplasm of treated breast cancer cells. In human breast cancer tissue, the compounds demonstrated increased binding as compared to the fluorophore. The new fluorescent CDK inhibitors showed undiminished activity in multidrug resistance (MDR) positive breast cancer cells, indicating that they are not a substrate for p-glycoprotein. Fluorescent CDK inhibitors offer potential as novel theranostic agents, combining therapeutic and diagnostic properties in the same molecule. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.02.052

文献信息

• METHODS AND COMPOUNDS FOR THE TREATMENT OF GENETIC DISEASE
  申请人：DESIGN THERAPEUTICS, INC.

  公开号：US20210283265A1

  公开（公告）日：2021-09-16

  The present disclosure relates to compounds and methods for modulating the expression of bean (brain expressed, associated with NEDD4) and treating diseases and conditions in which bean plays an active role. The compound can be a transcription modulator molecule having a first terminus, a second terminus, and oligomeric backbone, wherein: a) the first terminus comprises a DNA-binding moiety capable of noncovalently binding to a nucleotide repeat sequence TGGAA; b) the second terminus comprises a protein-binding moiety binding to a regulatory molecule that modulates an expression of a gene comprising the nucleotide repeat sequence TGGAA; and c) the oligomeric backbone comprising a linker between the first terminus and the second terminus.
• [EN] FLUORESCENT CDK INHIBITORS FOR TREATMENT OF CANCER<br/>[FR] INHIBITEURS DE CDK FLUORESCENTS POUR LE TRAITEMENT DU CANCER
  申请人：UNIV GEORGETOWN

  公开号：WO2010019967A1

  公开（公告）日：2010-02-18

  Disclosed are molecules and their synthesis,. The fluorescent moiety also facilitates screening, tracking, and pharmacodynamic studies of the drug in a biological system both in vitro and in vivo.
• Fluorescent cyclin-dependent kinase inhibitors block the proliferation of human breast cancer cells
  作者：Venkata Mahidhar Yenugonda、Tushar B. Deb、Scott C. Grindrod、Sivanesan Dakshanamurthy、Yonghong Yang、Mikell Paige、Milton L. Brown

  DOI：10.1016/j.bmc.2011.02.052

  日期：2011.4

  Inhibitors of cyclin-dependent kinases (CDKs) are an emerging class of drugs for the treatment of cancers. CDK inhibitors are currently under evaluation in clinical trials as single agents and as sensitizers in combination with radiation therapy and chemotherapies. Drugs that target CDKs could have important inhibitory effects on cancer cell cycle progression, an extremely important mechanism in the control of cancer cell growth. Using rational drug design, we designed and synthesized fluorescent CDK inhibitors (VMY-1-101 and VMY-1-103) based on a purvalanol B scaffold. The new agents demonstrated more potent CDK inhibitory activity, enhanced induction of G2/M arrest and modest apoptosis as compared to purvalanol B. Intracellular imaging of the CDK inhibitor distribution was performed to reveal drug retention in the cytoplasm of treated breast cancer cells. In human breast cancer tissue, the compounds demonstrated increased binding as compared to the fluorophore. The new fluorescent CDK inhibitors showed undiminished activity in multidrug resistance (MDR) positive breast cancer cells, indicating that they are not a substrate for p-glycoprotein. Fluorescent CDK inhibitors offer potential as novel theranostic agents, combining therapeutic and diagnostic properties in the same molecule. (C) 2011 Elsevier Ltd. All rights reserved.