The drug discovery market remains untapped with huge potential for new breakthroughs and innovations in creating better medicines. Researchers are actively exploring innovative approaches to overcome the challenges inherent in drug discovery. One such avenue in the field of integrins offers a unique opportunity to draw insights from past clinical trials, delve into new modalities and integrate the latest discoveries in pharmacology.

Recent developments highlight novel inhibitors of the integrins αvβ6 and αvβ1, emerging as subjects of clinical investigation for treating fibrotic diseases like idiopathic pulmonary fibrosis and nonalcoholic steatohepatitis. Integrin inhibition has resulted in a number of commercial medications, as well as ongoing preclinical research. Since 2015, at least 130 clinical studies of integrin-targeted therapeutics have been conducted.

Integrin biology

Integrins are heterodimeric cell surface receptors and are key regulators affecting cell morphology, proliferation, survival and differentiation. Mutations in specific integrins or deregulated expressions are associated with a variety of diseases. Each integrin consists of α-subunit and a β-subunit, of which there are 18 and 8 variants, respectively, creating 24 known heterodimers. Integrins act as adhesion receptors with the unusual ability to signal in both directions across the plasma membrane. Integrins can therefore enable human cells to respond to changes in the extracellular environment (via outside-in signalling) and can influence the extracellular environment (via inside-out signalling). 

Notability, a wide variety of integrins are found in humans with diversity in the ligands they bind to; the tissue specific expression of specific integrins and the resulting signalling pathways involved in integrin activation, make these attractive drug targets for a number of different diseases. For example, the RGD-binding family of integrins recognises the amino acid binding motif Arg–Gly–Asp (RGD) in their endogenous ligands. Yet, despite their apparent similarity, these integrins can readily distinguish between different RGD-containing ECM proteins (e.g., vitronectin, TGFβ, fibronectin), and respond differently to the interaction with each one of them.

(Image source – Nature Reviews, Drug Discovery: Vol 21, January 2022)

Driving Drug Discovery Forward

With the breadth and complexity within the integrin family, only a small component of integrin biology is understood and requires further research to fill in the gaps. Therefore development and testing of improved molecules are required to further dissect these complexities which could lead to the successful generation of integrin-targeting drugs and in treating multiple diseases.

Our o2h scientists are well positioned to  support our collaborators by utilising our extensive Integrated Drug Discovery  (IDD) experience in both our India and UK sites.

Biological assays

We have successfully established biochemical and cell-based assays to assess target engagement of small molecules for different integrin targets. Using this knowledge and experience, we are able to offer a highly customisable platform where we can establish the potency of a compound in cell adhesion assays & ELISA against multiple integrin targets and determine specificity profiles. Additionally, we are able to fully characterise these compounds in bespoke cellular assays using our flow cytometry & high-content imaging capabilities to determine their activity in a biological setting.

To know more about the o2h discovery Biology capabilities  and our broader services, then please email us at discovery@o2h.com or visit – https://o2hdiscovery.co/biology/