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.
Traditional drugs bind to the Active Site
- Competition with natural substrate can limit efficacy
- More off-target effects as sites are highly conserved across many proteins
Gain’s drugs target Allosteric Sites
- Non-competitive with natural substrate
- Highly specific and better drug properties
- Expands target universe
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.
Misfolded Protein
Gain Binds to Rescue Folding
Restored Protein Function- Gain of function approach
- Stabilizing native form of protein
- Restores natural protein function
Functional Protein
Gain Binds to Disrupt Folding
Loss of Protein Function
- Loss of function approach
- Allosteric PROTAC, targeted protein degradation
- Results in ubiquitination and protein degradation
Functional Protein
Ubiquitination at Allosteric Site
Loss of Protein Function
- Loss of function approach
- Stabilizing non-native form of protein
- Results in protein dysfunction and/or degradation
- Loss of function approach
- Changing active site conformation to inhibit binding
- 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.
