merck p53 stapled peptide patent EP3256484A1 pending - mer-peptide may penetrate cell membranes and bind to an intracellular receptor Merck's P53 Stapled Peptide Patent: Advancing Cancer Therapy Through Protein Stabilization

menopause-peptides The development of novel cancer therapeutics is a dynamic field, with significant advancements being made in understanding and manipulating cellular pathways critical to disease progression. Among these, the p53 tumor suppressor protein plays a pivotal role in preventing the development of cancer. However, its function is often compromised in various malignancies. A key area of research has focused on developing stapled peptides designed to reactivate the p53 pathway. This article delves into the work of Merck, exploring their merck p53 stapled peptide patent landscape and the implications of this innovative approach to cancer treatment.2017年8月10日—Stapled peptidesmay penetrate cell membranes and bind to an intracellular receptor. [0074] In one non-limiting example, the stapled peptide is ...

Understanding the p53 Pathway and the Role of Stapled Peptides

The p53 protein is a crucial guardian of the genome, acting as a transcription factor that regulates cell cycle arrest, DNA repair, and apoptosis (programmed cell death). In many cancers, the p53 gene is mutated or the protein is inactivated, allowing damaged cells to proliferate uncontrollably. A primary mechanism of p53 inactivation involves its interaction with oncoproteins like MDM2 and MDMX. These proteins bind to p53, marking it for degradation and thereby neutralizing its tumor-suppressive functions作者：MH Reutershan·2021·被引用次数：26—Design-rules forstapled peptideswith in vivo activity and their application to Mdm2/X antagonists. ... An updatepatentreview of MDM2–p53....

Stapled peptides represent a significant breakthrough in drug development because they are engineered to overcome the limitations of conventional peptides. By introducing a chemical "staple"—typically a hydrocarbon linker between specific amino acid residues—these molecules are locked into a stable α-helical conformation. This enhanced structural rigidity improves their stability in biological environments, increases their cell permeability, and allows them to bind with high affinity to their intended targets. In the context of p53, stapled peptides are designed to bind to MDM2 and MDMX, preventing them from degrading p53The Stapled Peptide PM2 Stabilizes p53 Levels and .... This disruption of the MDM2/MDMX-p53 interaction effectively reactivates the p53 pathway, leading to the selective killing of cancer cellsThe present invention relates tonon-membrane disruptive and p53 activating stapled peptides, as well as methods of treatment of cancer involving the use of ....

Merck's Patent Portfolio and Research in Stapled Peptides

Merck has been actively involved in the research and development of stapled peptides for therapeutic applications, particularly in oncology2025年5月15日—A new molecular dynamics study reveals how somestapled peptidesshapeshift to slip through cellular barriers and target key disease-related proteins within .... Their patent filings, such as those related to merck p53 stapled peptide patent initiatives, underscore their commitment to this cutting-edge technology.IDP-410: a Novel Therapeutic Peptide that Alters N-MYC ... These patents often describe novel stapled peptides with specific sequences and structural modifications designed to optimize their efficacy and safetyStapled Peptides and Method of Synthesis.

For instance, research has highlighted the development of compounds like MK-4688, which is described as an efficient inhibitor of the HDM2–p53 interactionNEW STAPLED-PEPTIDES AND USES THEREOF. This signifies a focused effort by Merck to create potent p53 activators. Furthermore, collaborations have been noted between Merck and academic institutions, leading to joint patent applications and publications. An example of this is the patent application EP3256484A1 pending, which involves Merck's collaboration on macrocyclic peptides.

The scientific literature also points to Merck's interest in non-membrane disruptive and p53 activating stapled peptides.Non-membrane disruptive P53 activating stapled peptides This specific focus suggests an effort to develop peptides that can effectively enter target cells without causing cellular damage, a critical factor for therapeutic safety and efficacy.作者：AR Shustov·2018·被引用次数：6—Pseudoprogression (PsP) in patients with peripheral T-cell lymphoma (PTCL) treated with the novelstapled peptideALRN-6924, a dual inhibitor of MDMX and MDM2. The ability of stapled peptides to penetrate cell membranes and bind to an intracellular receptor is a key advantage, enabling them to access targets that are typically inaccessible to larger molecules.作者：MR Schnorenberg·2023·被引用次数：12—In this work, we hypothesized thatp53reactivation using. ATSP-7041 would prime DLBCL for apoptosis via the BCL-2 family of proteins and ...

Key Innovations and Applications

The merck p53 stapled peptide patent landscape likely encompasses several key innovations:

* Novel Peptide Sequences and Architectures: Development of unique stapled peptide sequences that exhibit superior binding affinity and selectivity for MDM2 and MDMX. This includes exploring both L- and D-amino acid configurations, as mentioned in some research related to design-rules for stapled peptides with in vivo activity.NEW STAPLED-PEPTIDES AND USES THEREOF

* Enhanced Stability and Pharmacokinetics: Engineering stapled peptides with improved metabolic stability and longer half-lives in the body, potentially through modifications like conjugation to albumin-binding ligands.

* Targeted Delivery Systems: Investigating methods for delivering stapled peptides specifically to tumor sites, thereby minimizing off-target effects and enhancing therapeutic outcomes.(PDF) The Stapled Peptide PM2 Stabilizes p53 Levels and ... This could involve technologies like lipodisks for tumor-targeted delivery of p53-activating stapled peptidesP53 activator peptidomimetic macrocycles.

* Combination Therapies: Exploring the use of stapled peptides in combination with other cancer treatments to achieve synergistic effects.2022年9月14日—(i) providing a plurality ofpeptidescomprising protection groups, eachpeptidebeing immobilized on a solid support;. (ii) exposing a ...

The search intent surrounding "merck p53 stapled peptide patent" reveals a strong interest in understanding the specific stapled p53 peptides being developed, their mechanisms of action, and their potential for clinical application. Terms like "p53", "stapled", and "peptide" are central to this research, highlighting the core components of this therapeutic strategy.Phase I trial of a novelstapled peptideALRN-6924 disrupting MDMX- and MDM2-mediated inhibition of WTp53in patients with solid tumors and lymphomas. The inclusion of specific compound names like ALRN-6924 (though developed by other entities, it represents the broader field of stapled peptides as first-in-class clinical stage stapled peptides and cell-penetrating stapled alpha-helical peptides) and patent numbers like EP3256484A1 indicates a need for detailed technical and intellectual property information.

Future Directions and Conclusion

The ongoing research and patenting activities by Merck in the realm of p53 stapled peptides signify a promising avenue for cancer therapy. By stabilizing the p53 pathway, these peptides have the potential to address a wide range of cancers driven by p53 dysfunction. While challenges remain in translating these preclinical successes into widely available treatments, the continuous innovation in design-rules for stapled peptides with in vivo activity and the exploration of new therapeutic modalities, such as Raman active diyne-girder conformationally constrained p53 constructs, suggest a bright future for this fieldA technology of conjugates andstapled peptides, applied in the field of polypeptide drugs, can solve the problems of poor membrane permeability, .... The ability of these molecules to mimic the inhibitor of p53 suppression and restore normal p53-mediated apoptosis activity is a testament to their therapeutic potential. As research progresses, the merck p53 stapled peptide patent portfolio will likely continue to expand, contributing to the development of more effective and targeted cancer treatments.Raman active diyne-girder conformationally constrained p53 ...