About CoHead Therapeutics
Our History
COHead Therapeutics was founded in 2025 with the goal of developing new non-cystine targeting covalent inhibitors to improve the health of the patients with cancer.
Targeted Covalent Inhibitors (TCIs)
What are the covalent inhibitors ?
- Covalent inhibitors are revolutionizing drug discovery, offering unique advantages and significant therapeutic potential, particularly in cancer treatment. Unlike non-covalent inhibitors, covalent inhibitors selectively modify proximal nucleophilic amino acid residues on proteins, either reversibly or irreversibly, to achieve targeted and effective binding and therefore, covalent inhibitors can deactivate mutated proteins for extended periods, without extended toxicity. We have witnessed the power of covalent inhibitors through game-changing medications like Ibrutinib, Osimertinib and Sotorasib. Historically, most successful covalent inhibitors have relied on binding site of cysteine residues. However, this approach has limitations for proteins lacking targetable cysteines. Recent advancements have focused on designing covalent inhibitors and probes targeting alternative proximal nucleophilic residues, such as lysine, tyrosine and histidine.
Lysine's Potential
Lysine’s potential
- Cysteine is drug developer's top choice for a covalent target as it’s high reactivity with covalent inhibitors and lysine is the second choice. Lysine is abundant across the proteome and present in the sequence of most protein drug pockets. At the physiological pH (7.4), the solvent exposed lysines can be protonated and will no longer make a covalent bond. Therefore, drug discovery efforts can go after lysines nestled within the inner folds of a protein, where they are protected from protonation. To explore the extent of lysine’s potential, researchers recently charted the landscape of lysines in human proteins to look for druggable sites. Their effort showed plenty of opportunities in this relatively unexplored space. At COHEAD Therapeutics, we have developed a unique innovative platform (CovAI) to identify reactive non-cysteine residues including lysines and optimize potent, selective covalent inhibitors with unparalleled speed and accuracy. This innovative approach streamlines and accelerates our hit-to-lead process, enabling us to tackle challenging targets and deliver impactful solutions in cancer therapy.