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Yap1 inhibitors that target the interaction of yap1 with oct4

A C1-C8, C1-C6 technology, applied in medical preparations containing active ingredients, drug combinations, organic chemistry, etc., can solve problems such as low overall survival rate

Inactive Publication Date: 2019-06-04
H LEE MOFFITT CANCER CENT & RES INST INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Although chemotherapeutic agents such as gemcitabine, platinum compounds, and taxanes have improved survival to a limited extent, overall survival remains poor due to recurrence of more aggressive, drug-resistant tumors (Seve P et al. Chemoresistance in small cell lung cancer

Method used

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  • Yap1 inhibitors that target the interaction of yap1 with oct4
  • Yap1 inhibitors that target the interaction of yap1 with oct4
  • Yap1 inhibitors that target the interaction of yap1 with oct4

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Embodiment

[0215] The following examples are listed below to illustrate the methods and results according to the disclosed subject matter. These examples are not intended to cover all aspects of the subject matter disclosed herein, but to illustrate representative methods and results. These embodiments are not intended to exclude the equivalents and variations of the present invention, which are obvious to those skilled in the art.

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Abstract

Binding of the transcriptional co-activator, YAP1, to the transcription factor Oct4, induces Sox2, which is a transcription actor necessary for the self-renewal of stem-like cells from non-small celllung cancer. The WW domain of YAP1 binds to the PPxY motif of Oct4 to induce Sox2. Delivering a peptide corresponding to the WW domain could prevent the induction of Sox2 and stemness. Similarly, peptides and mimetics of the PPxY motif would be able to inhibit stemness. Disclosed are compounds that affect the Yap1:Oct4 interaction.

Description

[0001] Cross references to related applications [0002] This application claims the priority rights of U.S. Provisional Application 62 / 396,190 filed on September 18, 2016 and U.S. Provisional Application 62 / 396,383 filed on September 19, 2016. The entire contents of these two provisional applications are incorporated by reference. Into this article. Background technique [0003] Lung cancer is the leading cause of cancer-related mortality in the United States (Siegel R et al., Cancer Statistics, 2013. CACancer J Clin. 2013; 63(1): 11-30), of which most (85%) are caused by non-small Caused by cell lung cancer (NSCLC). Surgery is used to treat patients with early disease, but about 30-60% of them will develop recurrent tumors that lead to death (Demicheli R et al., the recurrence dynamics do not depend on the recurrence site. Breast Cancer Res. 2008; 10(5): R83; Demicheli R Et al. The recurrence dynamics of non-small cell lung cancer: the impact of surgery on the development of me...

Claims

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Application Information

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IPC IPC(8): C07D401/06C07D403/06A61K31/454A61K31/496
CPCC07D401/06A61K45/06C07D401/12C07D405/06C07D413/12C07D207/16C07D211/34C07D211/58C07D211/96A61P35/00C07C255/57C07C271/24C07C237/14C07C237/22C07C251/24C07C2601/14C07D211/32C07D403/06C07D241/04C07D211/14C07D211/56C07D233/64C07D263/32C07D257/04C07D233/92A61K31/454A61K31/496C07D211/60C07D401/10C07D405/12
Inventor 斯里库玛·希尔拉潘尼古拉斯·J·劳伦斯苏吉瓦·拉纳通加·马汉泽·穆迪扬塞拉格
Owner H LEE MOFFITT CANCER CENT & RES INST INC
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