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Ntcp inhibitor

A technology of inhibitors and co-transportation, applied in antiviral agents, medical preparations containing active ingredients, peptide/protein components, etc., can solve the problem of few effective methods

Pending Publication Date: 2020-10-30
THE UNIV OF TOKYO +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] For hepatitis B virus (HBV: Hepatitis B Virus), there are few effective methods among currently available therapeutic methods, and the development of new therapeutic methods is required

Method used

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Embodiment

[0166]Hereinafter, although an Example is shown and this invention is demonstrated concretely, this invention is not limited to a following Example.

[0167]

[0168] Material

[0169] Fmoc protected amino acids were purchased from MercK Millipore. Oligonucleotides were purchased from Eurofins GenomicsJapan. Other reagents were obtained from Nacalai Tesque, Inc. unless otherwise noted.

[0170] RaPID selection

[0171] Using known methods (Morimoto, J., Hayashi, Y. & Suga, H. Discovery of Macrocyclic Peptides Armed wit Ha Mechanism-Based Warhead: Isoform-Selective Inhibition of Human Deacetylase SIRT2. Angew. Chem. Int. Ed. Engl. 51, 3423 -3427(2012); and Kawakami, T., Murakami, H.&Suga, H. Messenger RNA-programmed incorporation of multiple N-methyl-amino acids into linear and cyclic peptides.Chem.Biol.15,32-42(2008 ) to synthesize cyanomethyl ester (CME) or dinitrobenzyl ester (DBE) activated amino acids. Aminoacylated ribozyme flexizyme and tRNA were prepared as f...

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Abstract

Provided is a sodium taurocholate cotransporting polypeptide (NTCP) inhibitor which comprises a cyclic peptide having an Xw1-W-Xw2-W structure (Xw1 and Xw2 are each independently T, S, I, L, or V, orN-alkyl amino acids thereof) or a P-Xp1-Xp2-H structure (Xp1 is an optional amino acid, and Xp2 is I, L, or V, or N-alkyl amino acids thereof), or a pharmaceutically acceptable salt thereof.

Description

technical field [0001] The present invention relates to NTCP inhibitors. Background technique [0002] For hepatitis B virus (HBV: Hepatitis B Virus), there are few currently available therapeutic methods that are effective, and development of new therapeutic methods is required. In this regard, in recent years, it has been known that hepatitis B virus (HBV) or hepatitis D virus (HDV: Hepatitis D Virus) infects cells by invading cells via sodium taurocholate cotransporting polypeptide (NTCP: Sodium Taurocholate Cotransporting Polypeptide) people, leading to the onset of hepatitis B. In contrast, as an attempt to treat hepatitis B by inhibiting NTCP, for example, studies have been conducted on the use of cyclosporin A (CsA: Cyclosporin A) and Myrcludex B (eg, Non-Patent Document 1). [0003] prior art literature [0004] non-patent literature [0005] Non-Patent Document 1: Nkongolo, S. et al., Cyclosporin A inhibits hepatitis B and hepatitis D virus entry by cyclophilin-...

Claims

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Application Information

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IPC IPC(8): A61K38/12A61P1/16A61P31/12A61P31/14A61P31/20A61P43/00C07K5/04C07K7/06C07K7/08
CPCA61P1/16A61P31/12A61P31/14A61P31/20A61P43/00C07K7/08A61K38/00C07K7/64
Inventor 菅裕明T·帕斯奥拉肋田隆字渡士幸一
Owner THE UNIV OF TOKYO
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