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.

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