Science

Some of the most impactful medicines in human history are underpinned by the irreversible modification of proteins by drug molecules. This irreversible modification provides durable engagement of the target by the drug, can increase selectivity of the drug, and in some cases leads to a drug effect that is disconnected from drug exposure.

  1. 1899

    Aspirin

    One of the most commonly taken drugs in the world

  2. 1928

    Penicillin

    A “miracle drug” that ushered in the era of antibiotics, revolutionized the treatment of infectious disease and saved millions of lives

  3. 1997

    Clopidogrel

    First-in-class anticoagulant used as the go-to treatment for reduction of atherothrombotic events for over a decade becoming one of the top selling drugs of its era

  4. 2003

    Bortezomib

    Cancer: Proteosome inhibitor that is part of the standard of care backbone of multiple myeloma treatment and approved in the US and EU for use across all lines of MM therapy

  5. 2017

    Osimertinib

    Cancer: A third-generation epidermal growth factor receptor (EGFR) inhibitor effective against the EGFR T790M mutation, which is estimated to be responsible for over half of all cases of resistance to early-generation EGFR tyrosine kinase inhibitors

  6. 2021

    Sotorasib

    Cancer: Approved for lung cancer patients with alteration in the gene KRAS, a target previously thought to be undruggable

Covalent, irreversible modification of a protein is a decades-old paradigm for the treatment of diseases and today, there are more than 50 approved drugs that act on their targets in this fashion.  Many of these drugs show selectivity, potency, and pharmacology that often surpasses conventional reversible drugs and afford patients differentiated therapy for their disease. 

Historically, many covalent drugs came from natural sources, were discovered by serendipity, or were created by the modification of potent and selective non-covalent drugs.  We see a future of broader impact unconstrained by history: at Aleksia, we are deploying covalency at all stages of drug discovery from the discovery of hits to the creation of differentiated molecules for clinical development and we are pioneering chemistry to expand the advantages of covalency to lysine, one of the most abundant amino acids found in proteins, and one of the most important amino acids for the function of numerous disease causing proteins.

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