Slider Pharma Research

Potential Research Questions

Which is the mode of action of this drug?
How can efficacy and toxicity be monitored?
Which biomarker profile predicts response to this drug?

Status Quo and Medical Need

For most drugs it is still not possible to predict which patient is going to respond based on pharmacogenetics alone. Attrition rates remain high, with limited knowledge about how the drugs work being among the reasons this is attributed to.

The response to drugs depends on much more than the genetic background of a patient. It is intuitively clear considering that a child will respond differently to a drug than an adult, and an adult will respond differently than an elderly patient; in spite of the genotype remaining unchanged.

Metabolomics is increasingly being used by pharmaceutical researchers as well as health authorities to gather additional information about how drugs work, how they cause toxicity, and which age or lifestyle factors might determine response.

Relevant Metabolite Classes

Phospholipids:

  • Lipid neogenesis is expected to increase upon mTOR activation.
  • Lipid metabolism is involved in the LDL lowering effect of metformin.

Acylcarnitines:

  • Acylcarnitines have been shown to be related to nephrotoxicity.
  • Mitochondrial beta oxidation may be relevant to assess activity of drugs that enhance mitochondrial function, such as pan-PPAR agonists.

Amino acids and biogenic amines:

  • The citrulline to arginine ratio as indicator for NO synthase activity is related to angiogenesis.
  • Amino acids, especially leucine and arginine, activate mTOR.
  • Tryptophan and kynurenine are the educt and product of the IDO pathway, a major immune regulatory pathway.

Bile acids:

  • Bile acids are expected to be altered in liver toxicity.
  • Upon administration of liver directed drugs, especially FXR or FGF19 inhibitors, biosynthesis may be altered.

Eicosanoids & Prostaglandins:

  • Prostaglandin synthesis is inhibited by COX-2 inhibitors (e.g. acetylsalicylic acid)

Selected Publications

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For Research Use Only. Not for use in diagnostic procedures.