Compositions and methods for modulating the activity of epstein-barr nuclear antigen 1

A composition and compound technology, applied in the direction of biochemical equipment and methods, drug combination, antineoplastic drugs, etc.

Inactive Publication Date: 2014-04-09
WISTAR INSTITUTE
View PDF4 Cites 7 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

During latent infection, EBV does not produce progeny virions, but expresses a limited set of viral gene products that promote host cell survival and proliferation

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Compositions and methods for modulating the activity of epstein-barr nuclear antigen 1
  • Compositions and methods for modulating the activity of epstein-barr nuclear antigen 1
  • Compositions and methods for modulating the activity of epstein-barr nuclear antigen 1

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0054] Example: Parallel Synthesis of Compounds

[0055]

[0056]

[0057] The substituents of the compounds synthesized according to Schemes 1-7 are listed in Table 1.

[0058] Table 1

[0059]

[0060] In addition to 3-nitro-benzofuran, other core structures are also envisioned, including but not limited to the following structures.

[0061]

[0062]

Embodiment 2

[0063] Example 2: Materials and methods

[0064] Expression and purification of recombinant EBNA1DBD. Amino acids 454 to 607 of EBNA1 encoding the DNA binding domain (GENBANK accession number YP_401677; SEQ ID NO: 1) were expressed in E. coli as a hexahistidine fusion protein. Expression was in Rosetta2 cells induced with 0.3 mM IPTG for 3 hours at 25°C. Soluble protein was recovered and purified by Ni-NTA agarose following standard methods (Frangioni & Neel (1993) Anal. Biochem. 210:179-87). The bound protein was extensively washed with 20 mM HEPES, pH 7.9, 1 M NaCl, 5 mM 2-mercaptoethanol, 40 mM imidazole and 10% glycerol to dissociate non-specific DNA bound to EBNA1, and then washed in a buffer containing 250 mM imidazole take off. Peak fractions of the eluted protein were pooled and dialyzed against 20 mM HEPES, pH 7.9, 500 mM NaCl, 5 mM 2-mercaptoethanol, 10% glycerol and 0.2 mM PMSF.

[0065]FP assay. The FP assay uses a probe with a non-palindromic site with two hi...

Embodiment 3

[0072] Example 3: Activity of Compounds

[0073] Compounds are screened for activity in the cell-based assays disclosed herein. Compound IC 50 The values ​​are listed in Table 2.

[0074] Table 2

[0075]

[0076]

[0077]

[0078]

[0079]

[0080] IC 50 Compounds at 125000 nM were inactive.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The present invention embraces compounds that modulate the activity of Epstein-Barr Nuclear Antigen 1 (BBNA1 ) protein and use thereof in methods for treating latent Epstein-Barr virus infection. R7 is a substituted or unsubstituted phenyl, pyridyl, or pyrimidinyl group. A pharmaceutical composition comprising a compound of the invention in admixture with a pharmaceutically acceptable carrier is also provide as are methods for modulating the activity of Epstein-Barr Nuclear Antigen 1 (EBNA1 ) protein and treating a latent EpsteinBarr virus infection with a composition of the present invention.

Description

Background of the invention [0001] This application claims the benefit of priority of US Provisional Application No. 61 / 489,293, filed May 24, 2011, the entire contents of which are incorporated herein by reference. [0002] Epstein-Barr virus (EBV) is an oncogenic cofactor for several lymphoid and epithelial malignancies (Kieff (2007), Epstein-Barr Virus and its Replication, vol. 5th Edition, Wolters Kluwer Health / Lippincott Williams & Wilkins, Philadelphia; Rickinson & Kieff (2007), Epstein-Barr Virus, 5th Edition, Wolters Kluwer Health / Lippincott Williams & Wilkins, Philadelphia; Young & Rickinson (2004) Nat. Rev. Cancer 4:757-68). EBV is associated with most prevalent forms of Burkitt's lymphoma and nasopharyngeal carcinoma (NPC). EBV is also present in ~50% of all Hodgkin's disease tumor biopsies, some forms of gastric cancer, thyroid tumors, NK / T-cell lymphomas, and most non-Hodgkin's lymphomas and lymphoproliferative disorders associated with immunosuppression Find. ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/70
CPCC07D407/04C07D307/82C07D405/12C07D413/04C07D413/12C07D307/79C07D405/04C07D417/12A61P31/22A61P35/00A61P43/00
Inventor 保罗·M·利伯曼特洛伊·梅西克
Owner WISTAR INSTITUTE
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap