Yissum - Research Development Company of the Hebrew University

Small Molecules Antagonists Of Toll Like Receptor 9 For Treatment Of Inflammatory Conditions

Posted by Yissum - Research Development Company of the Hebrew UniversityResponsive · Innovative Products and Technologies · Israel

Summary of the technology

Toll-like receptors, receptors of the innate immunity, play a critical role in the development of many pathological states, in acute and chronic inflammatory processes. Therefore, TLRs represent a new direction for immunotherapy. In order to discover novel ligands interacting with TLRs, Iterative Stochastic Elimination, an innovative beyond-state-of the-art in Silico method for predicting the chances of molecular bioactivity were employed (HUJI IDR). The most promising drug candidates were verified by a cell-based test-system (Fraunhofer IGB) that allows TLR antagonists/agonist to be identified in a reporter gene assay. The ISE process in addition with the assay lead to novel immune modulating therapeutics
Project ID : 6-2015-3128

Yissum - Research Development Company of the Hebrew University

Description of the technology


Life Sciences and Bio Technology


Iterative Stochastic Elimination (ISE), Ligands, TLRs

Current development stage

TRL3 - hypothesis testing and intial POC demonstrated in limited # of in-vitro models


  • Toll-like receptors (TLRs) have been implicated in several autoimmune and inflammatory diseases, including cancer, diabetes, cardiovascular disease, atherosclerosis, Alzheimer’s disease, and chronic neuropathic pain.
  • Currently, most of these life-threatening diseases do not have any treatments available in the market, representing unmet medical needs.
  • Three-dimensional structural data showing the ligand recognition mechanisms of all human TLRs (except for TLR10) have been deposited in public domains and encourage the development of TLR modulators (agonists and antagonists) to achieve various therapeutic goals.

Our Innovation

A novel immune modulating therapeutics based on 18 small molecules antagonists candidates newly discovered

  • Modulate immune response
  • Block multiple TLRs
  • Can be activated by endogenous molecules
  • Can be activated by low molecular weight synthetic compounds


  • Human TLRs can elicit overlapping yet distinct immune responses because of their ability to recognize an overlapping set of molecular patterns. Therefore, potent poly TLR antagonists need to be developed to block multiple TLRs.
  • A cell-based assay that mimics the innate immune system that includes all 10 human TLR-receptors was developed, screening 1.8 million molecules, providing 68 top candidates which were evaluated in an assay based on TLR9.
  • The process includes TLR9 data selection and preparation, followed by ISE algorithm method, MCC scoring method, virtual screening and in-vitro tests on cell-line.
  • Further candidate improvement was done using applicability domain filtering and solubility filtering.

Fig. 1: Schematic representation of the assay for TLR9 compound screening. Both antagonist and the specific ligand CpG ODN are added to the cell line leading to a blocking of TLR9.


  • Multi-targeted drugs development with simpler pharmacokinetics, lower drug resistance and greater dosing flexibility than traditional “one target-one drug”, “cocktails drugs” and “linked drugs”.
  • New drugs against viral infections, dermatologic, autoimmune and inflammatory diseases
  • Discovery of novel and different molecular active structures.

Project manager

Mel Larrosa
VP Business Development Healthcare

Project researchers

Amiram Goldblum
HUJI, School of Medicine - IMRIC
School of Pharmacy- Institute for Drug Research

HUJI, School of Medicine - IMRIC
School of Pharmacy- Institute for Drug Research

Related keywords

  • Medicine, Human Health
  • Biology / Biotechnology
  • Genome Research
  • Micro- and Nanotechnology related to Biological sciences
  • Recombinant DNA
  • Monoclonal Antibodies and Hybridomas
  • Gene Splicing and Manufacturing Equipment
  • Other Genetic Engineering
  • Molecular design Market
  • Microbiology Market
  • Micro- and Nanotechnology related to Biological sciences
  • Biochemistry / Biophysics Market
  • Toxicology Market
  • In vitro Testing, Trials Market
  • Stem cells and biobanks
  • Cellular and Molecular Biology Market
  • Population genetics Market
  • Gene Expression, Proteom Research Market
  • Bioinformatics Market
  • Enzymology/Protein Engineering/Fermentation
  • Genetic Engineering Market
  • Diagnostic
  • Therapeutic
  • Other Medical/Health Related
  • Anatomy, Pathology, Immunology, Physiology
  • Clinical Medicine
  • Life Science & Biotechnology
  • small molecule

About Yissum - Research Development Company of the Hebrew University

Technology Transfer Office from Israel

Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. Founded in 1964 to protect and commercialize the Hebrew University’s intellectual property. Ranked among the top technology transfer companies, Yissum has registered over 8,900 patents covering 2,500 inventions; has licensed out 800 technologies and has spun-off 90 companies. Products that are based on Hebrew University technologies and were commercialized by Yissum generate today over $2 Billion in annual sales.

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