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Integrin Receptors Targeted library

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ChemDiv’s library of small molecule compounds specifically targeting integrins contains 1,708 entries

Integrins are critical components of cellular machinery that mediate interactions between cells and their surrounding extracellular matrix (ECM). These interactions are crucial to a wide array of physiological processes, including tissue repair, immune response, and embryonic development. Integrins are heterodimeric transmembrane glycoproteins, composed of two different subunits: α (alpha) and β (beta). There are 24 known integrin subtypes, which are formed by various combinations of 18 alpha and 8 beta subunits. This diversity allows cells to engage with a wide variety of ECM proteins, including fibronectin, vitronectin, and collagen, through a specific sequence known as the RGD motif (Arginine-Glycine-Aspartic acid).

The interaction between integrins and the ECM is not only structural; it also mediates critical signaling pathways regulating cell adhesion, growth, proliferation, migration, survival, and invasion. These processes are essential for the normal functioning of cells and the maintenance of tissue integrity. The same mechanisms that support normal cellular functions can also contribute to the development and progression of diseases when dysregulated.

Integrins play a dual role in cancer development. They can support tumor growth and metastasis by facilitating tumor cell migration and invasion into surrounding tissues and blood vessels. At the same time, the dependency of tumor cells on integrin-mediated interactions for survival and growth provides a potential target for therapeutic intervention. Synthetic RGD peptides or peptidomimetics, which mimic the natural RGD motif found in ECM proteins, can interfere with integrin binding. By blocking this interaction, these agents can disrupt the downstream signaling pathways that promote tumor cell survival and proliferation, thereby inducing apoptosis (programmed cell death) in tumor cells. This therapeutic strategy highlights the importance of integrins in disease development and underscores their potential as targets for the development of novel treatments.

Beyond cancer, integrins are implicated in a variety of other diseases. In autoimmune diseases, aberrant integrin signaling can lead to inappropriate immune responses against the body's own tissues. In cardiovascular diseases, integrin-mediated processes are involved in the formation of atherosclerotic plaques and thrombosis. In fibrotic diseases, integrins contribute to the excessive deposition of ECM proteins, leading to tissue scarring and organ dysfunction.

Small molecule ligands targeting integrins offer a promising avenue for drug discovery, capitalizing on the pivotal role of integrins in mediating cell-ECM interactions. Designing ligands specifically binding to integrins helps modulate integrin signaling pathways to either inhibit or activate certain cellular responses. The versatility of integrin-ligand interactions opens the door to a wide range of therapeutic applications, from halting the spread of cancerous cells to moderating immune system dysregulation. The specificity of these ligands towards distinct integrin subtypes allows for targeted therapies with potentially reduced side effects, making integrin-targeting ligands a focal point in the development of new and more effective treatments.

Our library containing small molecules targeting integrins offers significant benefits for drug discovery, including high specificity and the ability to modulate a wide range of integrin-mediated pathways involved in disease progression. It helps with the rapid screening and identification of potential therapeutic agents that can selectively interact with various integrin subtypes, thereby facilitating the development of targeted treatments with fewer off-target effects. Our small molecules often have favorable pharmacokinetic properties, such as oral bioavailability and the ability to cross cell membranes, making them highly desirable candidates for developing new drugs for cancer, inflammatory, and autoimmune diseases.

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