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Agonist agents of cd47 inducing programmed cell death and their use in the treatments of diseases associated with defects in programmed cell death

一种空缺、性质的技术，应用在环肽模拟物领域，能够解决效力慢等问题

Active Publication Date: 2019-02-12
SORBONNE UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0038] However, although WO2013 / 182650 was able to specifically identify peptide sequences for cancer therapy, the peptides described in WO2013 / 182650 cannot be used for therapeutic purposes because their potency is still very slow and requires high peptide concentrations to trigger PCD (WO2013 / 182650 The most potent peptide described in , about 200 μM)

Method used

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  • Agonist agents of cd47 inducing programmed cell death and their use in the treatments of diseases associated with defects in programmed cell death
  • Agonist agents of cd47 inducing programmed cell death and their use in the treatments of diseases associated with defects in programmed cell death
  • Agonist agents of cd47 inducing programmed cell death and their use in the treatments of diseases associated with defects in programmed cell death

Examples

Experimental program
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Embodiment

[0189] 1. Synthesis and characterization of the cyclic peptide of the present invention

[0190] general method

[0191] All commercial chemicals and solvents were of reagent grade and used without further purification unless otherwise noted. All reactions, except those in aqueous media, were performed using standard techniques to exclude moisture. All reactions were performed under argon or nitrogen in oven-dried glassware using anhydrous solvents and standard syringe techniques. Protected amino acid derivatives, HATU, HBTU, HFIP, pseudoproline dipeptide and 2-CTC resins were purchased from Iris Biotech (Marktredwitz, Germany). DIPEA, NMP, piperidine solution, DMF, IPA, TFA, PyBOP were obtained from Sigma-Aldrich. Prepacked 2-CTC resin, Dmb-amino acid, PyOxim and Oxyma Pure were from Merck Novabiochem.

[0192] Solid-phase peptide synthesis was performed in polypropylene Torviq syringes fitted with polyethylene porous discs at the bottom and closed with suitable stopcoc...

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Abstract

The present invention relates to cyclic peptides mimetics of the C-terminal binding domain of TSP-1. The present invention also relates to the use of these cyclic peptides as agonists of CD47 and their ability to trigger programmed cell death (PCD). The present invention further relate to a pharmaceutical composition for use in the treatment of diseases associated with defects in PCD such as cancers and immunological disorders (including chronic inflammation) and comprising at least one cyclic peptide according to the invention.

Description

technical field [0001] The present invention relates to cyclic peptide mimetics of the C-terminal binding domain of TSP-1. [0002] The present invention also relates to the use of these cyclic peptides as CD47 agonists and their ability to trigger programmed cell death (PCD). [0003] The invention also relates to a pharmaceutical composition comprising at least one cyclic peptide of the invention for the treatment of PCD deficiency associated diseases such as cancer and immune disorders (including chronic inflammation). Background technique [0004] 1- The role of PCD in disease [0005] Programmed cell death (PCD) plays an important role in the regulation of development and tissue homeostasis, such as building structure and driving morphogenesis, regulating cell numbers, and eliminating unwanted potentially dangerous cells i . [0006] Dysregulation of this process (ie, PCD excess or deficiency) is associated with a variety of human diseases, including developmental an...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/08A61K38/12C07K7/50C07K7/64C07K14/78
CPCC07K14/70596C07K7/64C07K14/4705A61K38/00A61P37/06A61P29/00C07K14/47A61P35/00C07K7/50
Inventor P·喀罗岩
Owner SORBONNE UNIV
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