Small molecule binders of lysosomal proteins and glycosaminoglycans for eventual use as PET ligands | Medicine

Small molecule binders of lysosomal proteins and glycosaminoglycans for eventual use as PET ligands

Background
What we're looking for
What we can offer you
Who we are

Background

Lysosomal storage diseases (LSDs) comprise a class of almost fifty inherited metabolic disorders that may affect different parts of the body, including the skeleton, brain, skin, heart, and central nervous system. They are caused by an abnormal build-up of toxic metabolites in lysosomes as a result of enzyme deficiencies.

Takeda is a world leader in developing therapies to treat LSDs. We are currently seeking small molecule binders of glycosaminoglycans and/or lysosome associated proteins to further our therapeutic studies. We will use these small molecules to develop PET (positron emission tomography) ligands to assess the efficacy of various treatments for multiple LSDs, first in animal studies and then in humans. We would also welcome computational screening platforms that could identify such small molecules.

These PET ligands will be instrumental for our studies to understand how our therapies are affecting the pathology of the disease in real time, particularly in children and in the brain.

What we're looking for

We are seeking small molecule binders (< 1,000 Da) and/or binding motifs that can bind:

Glycosaminoglycans, particularly heparan sulfate
Sphingolipids
Lysosomal proteins

Solutions of interest include:

Small molecules with micromolar binding affinity to their targets
A computational screening platform for assessing and identifying polysaccharide-small molecule interactions

Our must-have requirements are:

Compounds or platforms that identify small molecules or natural products (< 1,000 Da) showing at least micromolar affinity to the target

Our nice-to-have's are:

Small molecules, peptidomimetics, short peptides, or natural products
Known interaction with heparin or heparan sulfate
Brain penetrance is highly valuable, but not necessary. We do not have strict criteria for affinity and mechanism of binding

What's out of scope: