ProxAI
Proof / Case Study 01 · CDC20
Case Study 01 · CDC20 · Proof of Concept

One Function Silenced.
A Small Molecule
Outperformed.

A single round of AI-generated de novo peptides against the CDC20 D-box degron interface more than doubled Apcin’s cell-death response in HeLa cells. Cell death measured by FACS.

Target
CDC20 · D-box
Modality
De novo peptide
Model
HeLa cells
Readout
FACS · N=3
2.7×
Potency vs Apcin
FACS · HeLa
1
Design round
No iterative optimization
9
Amino acids
De novo designed
Figure 1 · Primary readout

Cell death in HeLa cells, by dose

% cell death · FACS · N=3

Doses in µM. The dashed line marks Apcin’s highest response at the doses tested (21% at 300 µM).
The study
01

The challenge

CDC20 is an oncology target. Its function is controlled through the D-box, a small, groovy protein-protein interface. Small molecules bind it with medium affinity but are too small to block with efficacy natural peptide motifs from binding. Apcin, the reference inhibitor, shows weak activity even at high doses.

02

The approach

ProxAI designed with it's de novo platform 9-amino-acid peptides to bind the CDC20 D-box. Candidates were scored computationally and went straight into a cellular assay. One round of design. No iteration.

03

The result

The lead peptide, PRX-01, induced 56% cell death in HeLa cells, a 9.3x increase over the 6% negative control and more than double Apcin's response at matched doses. It matched Apcin's cell-death effect at a 2.7x lower concentration.

Methods & caveats

Readout: percent cell death by flow cytometry (FACS) in HeLa cells, N=3. Fold-changes computed from this readout: 9.3× is PRX-01 (56%) over the negative control (6%); potency comparison reflects the concentration required to reach a comparable cell-death effect versus Apcin. Results are from a single, unoptimized design round and represent a proof of concept, not a validated therapeutic. Absolute values depend on assay conditions and dose. Claims on this page reflect internal data and are subject to scientific review.

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Next: Case Study 02 · Inflammation

Surgical modulation of a flat interface.

82% suppression of a downstream inflammatory-pathway effector.

Read the case study