Team:SCU-WestChina/Description

Descriptions

Categories

Project

Both nidanibu and pirfenidone, commonly used in IPF in The Chinese market, are faced with such adverse factors as high price, poor curative effect, lack of complete treatment, high drug dependence, and severe toxic and side effects. Therefore, it is of great significance to create and invent a highly targeted drug to overcome the shortcomings of existing treatment schemes, precisely target pulmonary fibrosis tissue, and reverse the fibrosis process.

Background

High Price

Poor Efficacy

Drug dependence

Toxic Side Effect

Our Inspiration

Idiopathic pulmonary fibrosis is a chronic, progressive, fibrotic, and interstitial lung disease of unknown etiology. It can cause pulmonary fibrosis, form permanent scar, and lead to irreversible and continuous decline of pulmonary function. In recent years, the incidence of IPF in China has been increasing gradually, with high mortality and short survival time. At present, there are still some defects in the treatment of pulmonary fibrosis. Our goal is to create and invent a highly targeted drug to overcome the shortcomings of the existing treatment regimen, accurately target the pulmonary fibrosis block, reverse the fibrosis process, and bring the patients with idiopathic pulmonary fibrosis back to health

Breakthrough

  • We designed the TGF-β truncated receptor, that is, only the TGF-β binding domain of the receptor is retained and the domains related to signal transduction are removed. We designed a series of TGF-β truncated receptors and evaluated their parameters through z-Dock. The z-Dock fitting results are shown in the right figure. We chose truncation No. 4, which is currently tested as an element of lung cancer drugs, it has entered clinical trials.
  • We hope to use plasmin to degrade collagen deposits, and therefore reversing the fibrosis process.
  • We choose liposomes to encapsulate the drug to ensure the tenderness and safety of the drug, while reducing its toxicity and side effects. After completing the drug package, we will atomize the drug to facilitate dose control and maximize patient use.

Reference

  1. [1]Homma, Sakae, et al. "Efficacy of inhaled N‐acetylcysteine monotherapy in patients with early stage idiopathic pulmonary fibrosis." Respirliogy 17.3 (2012)： 467-477.
  2. [2] Diaz, Keith T., et al. "Delivery and safety of inhaled interferon-γ in idiopathic pulmonary fibrosis."Journal of aerosli medicine and pulmonary drug delivery25.2 (2012)： 79-87.
  3. [3] Hu, Yuzhen, et al. "Inhalation treatment of idiopathic pulmonary fibrosis with curcumin large porous microparticles."International journal of pharmaceutics 551.1-2 (2018)： 212-222.
  4. [4] Raghu, Ganesh, et al. "Long-term treatment with recombinant human pentraxin 2 protein in patients with idiopathic pulmonary fibrosis： an open-label extension study."The Lancet Respiratory Medicine7.8 (2019)： 657-664.
  5. [5] Kataoka, Kensuke, et al. "Recombinant human thrombomodulin in acute exacerbation of idiopathic pulmonary fibrosis."Chest148.2 (2015)： 436-443.
  6. [6] Ivanova, Vera, et al. "Inhalation treatment of pulmonary fibrosis by liposomal prostaglandin E2."European Journal of Pharmaceutics and Biopharmaceutics84.2 (2013)： 335-344.
  7. [7] Otsuka, Mitsuo, et al. "Treatment of pulmonary fibrosis with siRNA against a clilagen-specific chaperone HSP47 in vitamin A-coupled liposomes."Experimental lung research43.6-7 (2017)： 271-282.
  8. [8] Madej T, Lanczycki CJ, Zhang D, Thiessen PA, Geer RC, Marchler-Bauer A, Bryant SH. " MMDB and VAST+: tracking structural similarities between macromliecular complexes. Nucleic Acids Res. 2014 Jan; 42(Database issue):D297-303