Targeted Molecular Recognition
AngioDesign focuses on the rational design of enhanced, next-generation drugs for proven disease targets and its first target is Angiotensin-Converting Enzyme (ACE). AngioDesign is using 3-D structure-guided design to synthesize a new class of domain-selective ACE inhibitors, alone and in combination with other inhibitors, for cardiovascular and other non-communicable diseases.
Crystal structure of LisW-S in complex with tACE
N- and C-domains have different substrate affinities
Reversing the adverse effects of Ang and BK
Crystal structure of LisW-S in complex with ACE
Crystal structure of tACE, the equivalent of the C-domain
Surface and ribbon representations
Crystal structure of kAW in complex with tACE
Crystal structure of lisinopril
The figure on the left is a cartoon representation showing an overview of the tACE co-crystal structure with lisW-S.
The figure on the right is a stick representation showing lisW-S interactions in the active site: comparison between N- and C- domain residues.
Next-generation innovation combining clinical safety and efficacy
Differentiation – first-in-class dual C-domain/NEP inhibitors with blockbuster potential to treat hypertension and heart failure
AngioDesign has a well-differentiated alternative to existing heart drugs
The combination of a C-domain-selective ACEi plus an NEP inhibitor:
- Decreases blood pressure and normalises contraction of the blood vessels without influencing vascular permeability and endothelial cell function
- These features may be beneficial in the treatment of high blood pressure but without the side effects of cough and angioedema associated with the inhibition of NEP and the non-domain-selective inhibition of ACE
- This combination therapy has important clinical relevance and may be a new approach in the treatment of hypertension and heart failure.