Targeted Protein Degradation
• Controls protein quality throughout every cellular process
• A deep cleansing system in human body
• Redirects innate system to combat disease
Through reprogramming of the innate targeted protein degradation, BIGPRO® molecules can rejuvenate health and eliminate disease-causing proteins.
Proteostasis, or proteome homeostasis, is the controlled balance of protein synthesis, folding and degradation. It maintains a healthy cell environment and affects all cellular processes. The Ubiquitin Proteasome, the key component of a cell’s deep cleansing system, degrades proteins that were out-of-function, damaged, misfolded, and aggregated. It is the protein’s quality control system of the cell. Impaired proteostasis is a hallmark of aging and of many human diseases including cancer and neurodegeneration.
Protein disposal starts with tagging target proteins for degradation with a 76-amino acid peptide ubiquitin through a series of enzymatic reactions called ubiquitination. The ubiquitination complex consists of a ubiquitin activating enzyme (E1), ubiquitin conjugating enzyme (E2) and an ubiquitin ligase (E3). There are over 600 E3 ligases, 30 – 50 E2 conjugating enzymes, and 2 E1 enzymes in the human genome. After multiple rounds of ubiquitination, the poly-ubiquitinated target protein is then hydrolyzed by the 26S proteasome. The resulted building blocks are recycled.
BIGPRO® Protein Degrader
• Precise elimination of diseased protein
• Durable effect with improved safety
• Expanding towards the 80% unexplored undruggable targets
To return to the healthy state, diseased proteins can be redirected for degradation via AnHorn’s novel BIGPRO® (BI-functional liGand induced PROteolysis) molecules. One part is designed as a binder towards target protein whereas the other is fitted with a E3 ligase binder. Both parts are connected with a properly designed linker.
With the BIGPRO® molecule, target protein can be brought to close proximity of E3 complex for ubiquitination and subsequently are destroyed by the proteasome. Research since 2000 has shed light on the utility of this novel approach in fighting diseases. Targeted protein degradation has shown heightened potency, exceptional selectivity, and elimination of previously undruggable targets. Our novel BIGPRO® molecules are precision tools to correct cancer, neurodegeneration, and age-related diseases.
Novel E3 (E3 Ligase) with Effective Binder
• Identifying novel E3 ligases with disease relevance.
• Designing effective binders with desirable effect.
Human proteome is equipped with more than 600 E3 ligases for substrate protein engagement and the regulation of protein degradation. Nowadays only a handful of E3 ligases have been studied in detail.
The identity of E3 ligase towards previously undruggable targets and its suitability to rejuvenate health await further investigation. It is AnHorn’s commitment to identify novel E3 enzymes with a clear disease involvement to expand our target coverage. Effective binders can be designed and evaluated through our AIMCADD® platform.
• AnHorn‘s proprietary research engine for autonomous drug design and optimization
• High success rate with efficiency
• An approach with Systems Pharmacology considerations
The road from bench-to-bedside is a lengthy and expensive process with repeated trial-and-error and low success. Many of the discovery programs were plagued with compromises resulting in medicine frequently not living up to its potential. Smart design with a holistic and systems pharmacological approach that encompasses the field’s knowledge and internal research will not only facilitate efficiency but also the success of drug design.
We are leveraging our expertise in medicinal chemistry, bioinformatics, and computer-aided drug design with years of drug discovery and development experience to build the AIMCADD® platform. This platform is AnHorn‘s proprietary research engine for autonomous drug design and optimization. Both small molecular inhibitors, target binders, as well as protein degrading BIGPRO® molecules can be designed and evaluated. Novel treatments can be brought to patients faster with shortened discovery processes using AIMCADD®.