DNA-ENCODED CHEMICAL LIBRARIES

DNA-ENCODED CHEMICAL LIBRARIES

 

Philochem has pioneered the emerging field of DNA-encoded medicinal chemistry that allows the construction of large collections (or “libraries”) of chemical compounds with unprecedented size and functionality. The chemical compounds are individually coupled to distinctive DNA fragments, serving as amplifiable identification barcode, which can be identified by high-throughput sequencing.

The DNA-encoded library (DEL) technology opens new possibilities for the development of innovative drugs and enables the generation of small molecule targeting agents with antibody-like properties in a more cost-effective way than conventional high-throughput screening campaigns.

Philochem owns proprietary technologies and large DNA-encoded chemical libraries containing more than one billion compounds. These libraries are being used both for in-house discovery activities and for partnered programs.

 

 

Philochem has been the first company to describe DNA-recorded synthesis methods and high-throughput DNA sequencing for the construction and decoding of DELs. Philochem´s libraries contain billions of compounds, which can be screened in a few days in an inexpensive fashion, yielding ligands to proteins of pharmaceutical interest. Screening and hit validation procedures using DELs are cheaper and faster compared to other high-throughput platforms currently applied in drug discovery.

Philochem is a pioneer in exploiting the DEL technology for the discovery of high-affinity small molecule ligands specific to tumor-associated antigens. The tumor targeting potential of identified ligands is validated by in vivo imaging of cancer patients. Validated ligands are conjugated to cytotoxic drugs or radionuclides to generate small molecule drug conjugates (SMDCs) or radio conjugates (SMRCs).

 

 

Due to the proprietary encoding strategy, Philochem practices the DEL technology using proprietary Single-Pharmacophore libraries and Dual-Pharmacophore Encoded Self-Assembling Chemical (ESAC) libraries. The two technologies are complementary and contribute to a high success rate for the identification of high-quality ligands against “difficult” target proteins.

While Single-Pharmacophore libraries contain a high diversity of “lead-like” compounds, Philochem´s Dual-Pharmacophore libraries are formed by hybridization of two individually synthesized sub-libraries resulting in a combinatorial library of extreme purity and diversity.

Our scientists are constantly investing in the development of Philochem´s proprietary DEL platform and related enabling technologies.

 

 

The collaborative structure offered by Philochem allows a flexible screening of binders against few or several targets, based on the needs of the Partner. A typical project includes the screening of multiple libraries against several targets in various different experimental conditions. Library screening experiments are complemented by ligand validation activities using state-of-the-art methodologies for the characterization of affinity constants and ligand potency.

A typical collaborative structure consists of the following three steps on a target by target basis:

  • Step 1: Library Screening
  • Step 2: Ligand Validation
  • Step 3: Unblinding and Option Exercise

After the Option Exercise, the Partner will not have to pay any additional Milestones or Royalties.

 

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