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Arginase Targeted Library

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ChemDiv’s library of chemically diverse compounds targeting Arginase type 1 contains 2,016 molecules

In humans, arginase exists in two isoforms: Arginase 1 (Arg1), which is located in the cytosol, and Arginase 2 (Arg2), found within the mitochondria. Both isoforms are responsible for catalyzing the hydrolysis of L-arginine to L-ornithine and urea. This reaction is facilitated by one hydroxide ion and two manganese ions. This enzymatic process is not only crucial for the urea cycle and ammonia detoxification but also plays a significant role in several pathological conditions. Arginase has been implicated in cancer immunosuppression and tumor growth through the activity of Arg1 produced by myeloid-derived suppressor cells. The increased metabolism of L-arginine by these cells leads to the inhibition of the T lymphocyte response, a mechanism that tumors exploit to evade the immune system. Beyond cancer, arginase activity is associated with a variety of other diseases, including asthma, where it affects airway inflammation and responsiveness; erectile dysfunction, through its regulation of nitric oxide production; cystic fibrosis, by altering L-arginine bioavailability; and atherosclerosis, where it influences endothelial function and vascular tone. Thus, arginase plays a pivotal role in both physiological processes and the development of multiple diseases, highlighting its potential as a target for therapeutic intervention.

Targeting Arg1 presents a compelling avenue for drug discovery, offering potential therapeutic benefits across a broad spectrum of diseases. The multifaceted role of Arg1 in various physiological and pathological processes underscores its utility as a target in drug discovery, with the potential to yield treatments that address unmet medical needs across a diverse range of therapeutic areas.

Our library of small molecule compounds targeting Arginase 1 holds significant promise for drug discovery, particularly for conditions where Arg1 plays a critical role, such as cancer, cardiovascular diseases, asthma, and autoimmune disorders. By focusing on Arg1, our library enables the identification of inhibitors that can modulate the enzyme's activity, potentially restoring normal immune function in cancer by alleviating the immunosuppressive environment that allows tumors to evade immune surveillance. In diseases characterized by endothelial dysfunction, such as atherosclerosis, targeting Arg1 can improve vascular function by increasing the availability of L-arginine for nitric oxide synthesis, thus enhancing vasodilation and cardiovascular health. Additionally, in conditions like asthma and cystic fibrosis, Arg1 inhibitors can help to normalize L-arginine metabolism, reducing airway inflammation and improving lung function. The diversity of compounds within such a library allows for the exploration of different chemical structures and mechanisms of action, facilitating the optimization of drug candidates for better efficacy, safety, and patient outcomes. This targeted approach not only speeds up the drug development process by focusing on a specific therapeutic target but also offers the potential for novel treatments that address the underlying mechanisms of disease, opening new pathways for the management and treatment of diverse pathological conditions.

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