leo piper,Understanding Leo Pharma’s PPI Modulator: A Detailed Insight

Understanding Leo Pharma’s PPI Modulator: A Detailed Insight

Leo Pharma, a renowned pharmaceutical company, has made significant strides in the field of drug discovery and development. One of their latest achievements is the discovery of an IL-17A PPI modulator. In this article, we delve into the details of this innovative drug and its potential impact on the pharmaceutical industry.

What is IL-17A PPI Modulator?

The IL-17A PPI modulator is a small molecule inhibitor designed to target the interleukin-17A (IL-17A) pathway. This pathway plays a crucial role in various inflammatory and autoimmune diseases, such as psoriasis, rheumatoid arthritis, and inflammatory bowel disease. By modulating the IL-17A pathway, the drug aims to reduce inflammation and alleviate symptoms associated with these conditions.

Targeting a Validated Target

IL-17A is a validated target for drug development in the treatment of autoimmune and inflammatory diseases. Several antibody drugs, such as secukinumab, ixekizumab, and bimekizumab, have already been approved for treating psoriasis and related inflammatory diseases. These drugs target the IL-17A receptor (IL-17RA) or its associated pathways. However, the development of a small molecule drug with similar efficacy and oral bioavailability would be highly attractive.

Challenges in Developing Small Molecule Inhibitors

One of the challenges in developing small molecule inhibitors for the IL-17A pathway is the lack of a suitable binding pocket for small molecules. The IL-17A interface, known as the PPI (protein-protein interaction), is a large and complex structure, making it difficult to design small molecules that can effectively inhibit it. Additionally, the bRo5 (bromodomain and extraterminal domain) of the IL-17A interface is another obstacle, as it is difficult to achieve good oral absorption with small molecules of this size.

Leo Pharma’s Breakthrough

LEO Pharma has successfully addressed these challenges by developing a novel small molecule inhibitor, or PPI modulator, for the IL-17A pathway. This inhibitor, known as cmpd 1, has been shown to bind to two interfaces of the IL-17A dimer, making it a potential therapeutic candidate for treating inflammatory and autoimmune diseases.

Development Process

The development of cmpd 1 involved a combination of rational drug design and computational methods. The researchers at LEO Pharma analyzed the crystal structures of the previously reported IL-17A small molecule inhibitors and identified key features that could be used as a template for designing a new inhibitor. By modifying and optimizing these features, they were able to create cmpd 1, which has shown promising results in preclinical studies.

Comparison with Pfizer’s PPI Inhibitor

In a comparison with Pfizer’s PPI inhibitor, cmpd 1 has shown similarities in its binding mode and interaction with the IL-17A dimer interface. Both cmpd 1 and Pfizer’s inhibitor bind to the IL-17A dimer interface and exhibit similar binding modes. This suggests that cmpd 1 could be a potential therapeutic candidate for treating inflammatory and autoimmune diseases.