Target Protein Degradation - Proteolysis Targeting Chimera (PROTAC)

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Proteolysis Targeting Chimera

• Profacgen

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• In mammalian cells, protein degradation is mainly
  carried out by the ubiquitin-proteasome system to
  dispose of damaged or redundant proteins.
  Ubiquitin can be attached to the substrate
  protein through a series of enzymatic reactions
  leading to the covalent bonding between the
  C-terminal glycine of ubiquitin and the lysine
  residue of the substrate. Ubiquitin-tagged
  proteins are eventually recognized and destructed
  by proteasome. In spite of the high complexity of
  ubiquitin system, it is not surprising that some
  components or processes in this system could
  provide promising therapeutic intervention for a
  variety of diseases, including cancer and
  neurodegenerative diseases. One good example is
  the E3 ligases, which regulate the attachment of
  ubiquitin tags to substrate proteins for
  subsequent degradation.

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Illustration of the PROTAC strategy
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• Recently, Arvinas has developed a chemical
  strategy called Proteolysis Targeting Chimera
  (PROTAC) for E3 ligase-based degradation of
  target proteins.1 In principle, this method can
  be used to selectively degrade any protein of
  interest by bringing the target protein into
  proximity of the E3 ligase for proteasome-mediated
  proteolysis. Pioneered by Arvinas, PROTAC is
  becoming an promising strategy to target the so
  called undruggable proteins such as
  estrogen-related receptor alpha, cellular
  retinoic acid binding proteins, and BRD4.2 The
  key step of PROTAC is the construction a
  heterobifunctional small molecule that has two
  warheads one binds to the target protein, and
  the other recruits the E3 ligase. 

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• Profacgen, a leading biotech CRO, has been
  extensively working on bioconjugation services
  and assay development for more than a decade.
  Inspired by the discovery of PROTAC, we now offer
  small molecule-based conjugation services to help
  our customers develop a new class of therapeutic
  agents targeting cancers and other
  difficult-to-treat diseases. This
  degradation-oriented method is generally more
  advantageous than traditional enzyme inhibitory
  strategy in that PROTAC can

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• Remove target proteins rather than blocking them
• Avoid using high dosage to achieve sufficient
  inhibition
• Reduce toxicity
• Degrade uninhibitable proteins.

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• Our services consist of different modules that
  cover every aspect of PROTAC development, from
  ligand identification to biological evaluation.
  Customers are encouraged to choose individual
  modules that best fit their needs. To achieve the
  best efficacy, we do recommend our one-stop
  service package that delivers unrivaled value and
  will take care of your research project from
  scratch to full development.  

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Ligand identification
Affinity assays to confirm binding
potency,Structural modification, molecular
docking.
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Chemical conjugation
Modification of ligands, linker
development,conjugation chemistry, full
characterization.
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Biological evaluation
Enzyme inhibition, protein degradation, in
vitroADME, in vivo tests on animal models.
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• Contact Profacgen
• Address 45-1 Ramsey Road Shirley, NY 11967, USA
• Website https//www.profacgen.com