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Science
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.
![moleculeTherapies](/images/science/moleculeTherapies.png)
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.
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Allosteric Mechanisms
STABILIZATION
![STABILIZATION-FunctionalProtein](/images/science/STABILIZATION-FunctionalProtein.png)
Misfolded Protein
![SRABILIZATION-GainBindstoRescueFolding](/images/science/SRABILIZATION-GainBindstoRescueFolding.png)
Gain Binds to Rescue Folding
![SRABILIZATION-ProteasonalDegradation](/images/science/SRABILIZATION-ProteasonalDegradation.png)
Restored Protein Function
- Gain of function approach
- Stabilizing native form of protein
- Restores natural protein function
DESTABILIZATION
![DESTABILIZATION-FunctionalProtein](/images/science/DESTABILIZATION-FunctionalProtein.png)
Functional Protein
![DESTABILIZATION-GainBindstoDisruptFolding](/images/science/DESTABILIZATION-GainBindstoDisruptFolding.png)
Gain Binds to Disrupt Folding
![DESTABILIZATION-LossofProteinFunction](/images/science/DESTABILIZATION-LossofProteinFunction.png)
Loss of Protein Function
- Loss of function approach
- Allosteric PROTAC, targeted protein degradation
- Results in ubiquitination and protein degradation
Degradation
![Degradation-FunctionalProtein](/images/science/Degradation-FunctionalProtein.png)
Functional Protein
![Degradation-UbiquitinationatAllostericSite](/images/science/Degradation-UbiquitinationatAllostericSite.png)
Ubiquitination at Allosteric Site
![Degradation-ProteasonalDegradation](/images/science/Degradation-ProteasonalDegradation.png)
Loss of Protein Function
- Loss of function approach
- Stabilizing non-native form of protein
- Results in protein dysfunction and/or degradation
Allosteric Inhibition
Inhibitor Binds
![AllostericInhibition-1](/images/science/AllostericInhibition-1.png)
Active Site Changes
![AllostericInhibition-2](/images/science/AllostericInhibition-2.png)
Substrate Can't Bind
- Loss of function approach
- Changing active site conformation to inhibit binding
Activation
Allosteric Activation
![AllostericActivation-1](/images/science/AllostericActivation-1.png)
Active Site Changes
![AllostericActivation-2](/images/science/AllostericActivation-2.png)
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
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