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Ladon Therapeutics brings together breakthrough artificial amino acid-based small molecule (A3SMO®) chemistry and a state of the art diagnostic laboratory from gene expression profiling to in vivo disease models to characterize, test and evaluate A3SMO® drug candidates.
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The utilization of artificial amino acids enhances the stability of the 3D conformation. This results in an entropically more favoured receptor binding profile.
Longer half-life under physiological condition due to resistance to hydrolysis and enzymatic digestion.
The introduction of positively charged residues in combination with a restricted secondary structure enables cell-membrane penetration.
A3SMO® overcomes the limitation both of small molecules and biologics. These ligands can interact with protein surfaces with high affinity and selectivity. The drawbacks of biologics are overcome by A3SMO®: oral bioavailability, lack of immunogenicity, better tissue penetration, etc.
Small concave pocket is needed for stable binding
Smaller interacting surface is available
Unable to bind to large, flat interacting surfaces due to:
A3SMO® readily binds to large, water exposed interacting surfaces
Able to block PPIs
A3SMO® with stable 3D structure offers:
Can interact with larger molecular surfaces
Poor delivery efficiency of binding moiety as large, non-interacting scaffold is needed for molecular stability
Able to block PPIs
Immunogenic
No oral bioavailability
A3SMO® is resistant to acidic pH and to enzymatic cleavage by pepsin.
A3SMO® is resistant to water hydrolysis at neutral pH and to enzymatic cleavage by trypsin.
At pH 1.2
At pH 1.2
At pH 7.4
At pH 7.4 & trypsin
The difference between the A3SMO® and the reference compound includes β-amino acid substitution(s)
The A3SMO® has a significantly longer half-life
HT based artificial amino acid-based small molecules synthesis and target identification & validation significantly reduce time to select lead candidates for drug development.
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Gene expression analysis
Protein expression analysis
Histology
Immunohistochemistry
Immunofluorescent staining
2D cell culture models
3D organoid culture models
Signal transduction pathways
In vitro disease modelling
In vivo disease modelling
In vivo drug distribution analysis
A3SMO® are regulated by the FDA as small molecules
Robust and scalable manufacturing process
Traditional formulation approaches
Specialized CDMOs for commercial scale manufacturing
Comparable COGs with small molecule development and manufacturing
Capsules
A3SMO® are regulated by the FDA as small molecules
Robust and scalable manufacturing process
Capsules
A3SMO® are regulated by the FDA as small molecules
Robust and scalable manufacturing process
Immediate release tablets
Delayed release tablets
Controlled release tablets
Metered-dose inhaler (MDI)
Dry powder inhaler (DPI)
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