New Pharmacological paradigm

The traditional occupancy-driven pharmacology is based on the development of small molecules as binders or inhibitors of the target’s active or allosteric sites to block its function. High affinities and/or high doses are commonly mandatory for these drugs.

Mission

At Circa Therapeutics, we seek to pioneer a disruptive approach to disease treatment by developing small molecules for targeting and degrading disease-related proteins. Our proprietary protein degraders leverage the cell’s natural protein disposal system to target and eliminate disease-causing proteins. Our approach focuses on targeting proteins linked to rare diseases that lack traditional druggable targets. By pioneering new E3 ligase binders, we aim to expand the potential of degrader-based therapies to treat a wide range of conditions.

Vision

Our vision focuses on reinventing the treatment of human diseases by applying innovative therapeutics based on molecular induced proximity modalities.

Proteasomal Degradation

Most of intracellular proteins are degraded in a pathway mediated by three enzymes (E1, E2 and E3). E1 transfers ubiquitin to E2.
E3 recognizes the substrate protein and interacts with E2 which transfers the bound ubiquitin. The poly-ubiquitinated protein is directed to the 26S proteasome where it is degraded by proteolytic enzymes.

Targeted Protein Degradation

Small molecule degraders are, in essence, catalysts of protein degradation. They operate by undergoing multiple degradation cycles, which allows them to be administered in lower doses compared to drugs that function through an occupancy-driven mechanism. Degrading the target instead of blocking it expands the druggable proteome.

Catalytic mechanism

The catalytic mechanism implies that each degrader molecule cuts out more than one copy of the target protein

High selectivity

The careful design of these molecules permits high selectivities towards the target proteins and organs or tissues

Repurposing

Since high affinities are not required, there is a second window of opportunity for previously discarded drugs in traditional drug discovery campaigns

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