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Allosteric Innovation Next-Gen Therapies

Allosteric Innovation
Gain Therapeutics Inc.
Discovering and developing the next generation of allosteric small molecule therapies

Allosteric binding occurs when a molecule binds to a protein at a site other than the enzyme’s active site where the enzyme typically performs its function. The term comes from the Greek word for other site”. This allosteric interaction leads to a conformational change of the protein, which changes the protein’s affinity for a substrate.

Allosteric Innovation

Traditional drugs bind to the Active Site

Gain’s drugs target Allosteric Sites

Allostery offers a degree of control that is unattainable when targeting the active site, allowing researchers to fine-tune how a drug will alter the activity level of a specific protein in a specific disease. Gain’s allosteric modulators are disease-agnostic and designed to modulate a protein to restore or disrupt function as needed via stabilization, destabilization, degradation, inhibition or activation.

Allosteric Mechanisms

Misfolded Protein

Misfolded Protein

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Gain Binds to Rescue Folding
Gain Binds to Rescue Folding
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Restored Protein Function
Restored Protein Function
  • Gain of function approach
  • Stabilizing native form of protein
  • Restores natural protein function

Functional Protein

Functional Protein

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Gain Binds to Disrupt Folding

Gain Binds to Disrupt Folding

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Loss of Protein Function

Loss of Protein Function

  • Loss of function approach
  • Allosteric PROTAC, targeted protein degradation
  • Results in ubiquitination and protein degradation

Functional Protein

Functional Protein

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Ubiquitination at Allosteric Site

Ubiquitination at Allosteric Site

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Loss of Protein Function

Loss of Protein Function

  • Loss of function approach
  • Stabilizing non-native form of protein
  • Results in protein dysfunction and/or degradation

Inhibitor Binds

Inhibitor Binds
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Active Site Changes

Substrate Can’t Bind
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Substrate Can’t Bind

  • Loss of function approach
  • Changing active site conformation to inhibit binding

Allosteric Activation

Allosteric Activation
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Active Site Changes

Substrate Bind
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Substrate Bind

  • Gain of function approach
  • Changing active site conformation to induce binding

At Gain, we’ve developed a sophisticated, automated, selective and high-throughput method for drug discovery that is both highly efficient and cost-effective. Our streamlined approach dramatically shortens the conventional drug discovery timelines, enabling life-saving medications to reach patients sooner.

Posters

FENS Forum 2024

GT-02287, a Clinical-Stage GCase Enhancer, Improves Activities of Daily Living and Cognitive Performance in a Preclinical Model of GBA1 Parkinson’s disease

AD/PD™ 2024

Gt-02287, A Clinical Stage Glucocerebrosidase Regulator For The Treatment Of Pd, Eases Er Stress And Enhances Lysosomal Enzyme Activity

20th Annual WORLDSymposium®

GT-02287, a clinical stage GCase enhancer, displays neuroprotection and restores motor function in preclinical models of Parkinson’s disease following delayed administration
Publications

PLOS One

Discovery of allosteric regulators with clinical potential to stabilize alpha-L-iduronidase in mucopolysaccharidosis type 1

PLOS One

Validation of a highly sensitive HaloTag-based assay to evaluate the potency of a novel class of allosteric β-Galactosidase correctors-min

Nature Scientific Reports

Tau accumulation in degradative organelles is associated to lysosomal stress