merck p53 stapled peptide patent peptide - mersacidin-solid-phase-peptide-synthesis EP3256484A1 pending Merck's P53 Stapled Peptide Patent: Advancing Cancer Therapy Through Protein Stabilization

mental-health-peptides Merck's pursuit of innovative cancer therapies has prominently featured the development and patenting of stapled peptides, particularly those targeting the p53 tumor suppressor pathway. This strategic focus aims to reactivate the p53 protein, a crucial cell regulator that is frequently inactivated in various cancers, thereby inhibiting tumor growthStapled peptide conjugate for degrading MDM2/MDMX .... The merck p53 stapled peptide patent landscape highlights a sophisticated approach to drug development, where chemical modifications to natural peptides enhance their stability and therapeutic efficacy.

At the core of this research are stapled peptides. These modified peptides are engineered with an artificial cross-link, often referred to as a "staple," that spans across an alpha-helical structure. This structural reinforcement significantly improves the peptide's stability in biological environments, preventing its degradation and prolonging its therapeutic action. This innovation is critical because natural peptides, while potent, are often susceptible to rapid breakdown by cellular proteasesLong-acting dual GIP/GLP-1 peptide conjugates and methods .... The "stapling" technique allows for the creation of stapled peptides that mimic the natural interactions of proteins but with enhanced pharmacological propertiesThestapled p53 peptidesare thought to interfere with binding ofp53to HDM2 thereby inhibiting the destruction ofp53. Thestapled p53 peptidedescribed ....

A key target for these stapled peptides is the disruption of interactions between p53 and its negative regulators, specifically MDM2 and MDMX. These oncoproteins bind to p53, marking it for degradation and thus neutralizing its tumor-suppressing functions2025年10月17日—Tumor-targeted delivery ofstapled peptidesby use of lipodisks may therefore increase the uptake in the tumors and limit toxicity in healthy .... Stapled p53 peptides are designed to bind to MDM2 and MDMX, displacing p53 and allowing it to become active again. This activation can then trigger apoptosis (programmed cell death) in cancer cells or halt their proliferation. The non-membrane disruptive p53 activating stapled peptides represent a significant advancement, suggesting improved cellular penetration and targeted delivery without compromising cell integrity2017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 ....

Several patented technologies and research efforts underpin Merck's involvement in this field. For instance, patents like US9527896B2 describe "Stabilized p53 peptides and uses thereof," detailing how these modified peptides interfere with the MDM2 binding, thereby inhibiting p53 destruction. Furthermore, collaborations and patent filings, such as the mention of EP3256484A1 pending, indicate ongoing research and development, potentially involving specific compounds like PM2.

The development of ALRN-6924, a cell-penetrating stapled alpha-helical peptide, exemplifies the clinical progression of this technology. Described as the first-in-class clinical stage stapled peptide, ALRN-6924 is designed to equipotently disrupt the interaction between the p53 tumor suppressor protein and its regulators. Clinical trials, including Phase I and Phase II studies, have investigated ALRN-6924 for its efficacy in patients with solid tumors and lymphomas, assessing its potential to restore normal p53-mediated apoptosis activity. This drug also functions as a dual inhibitor of MDMX and MDM2, underscoring the therapeutic strategy of targeting multiple regulatory proteinsP53 activator peptidomimetic macrocycles.

The application of stapled peptides extends beyond direct inhibition of MDM2 and MDMX.作者：J Charoenpattarapreeda·2021—This thesis presents two approaches towards the development of novel bioactive molecules with application in cancer therapeutics. 1) Development ofstapled... Research into non-membrane disruptive and p53 activating stapled peptides also explores methods for effective delivery and targeting. Techniques involving targeted polymersome delivery of a stapled peptide and the use of lipodisks aim to enhance tumor uptake and minimize toxicity to healthy tissues.2024年1月12日—Althoughstapledα-helicalpeptidescan address challenging targets, their advancement is impeded by poor understandings for making them ... This focus on formulation and delivery is critical for translating the promise of stapled peptides into effective clinical treatments.

The scientific literature also details the underlying design principles for these advanced molecules. For example, the concept of design-rules for stapled peptides with in vivo activity is crucial for optimizing their therapeutic potential.Non-membrane disruptive p53 activating stapled peptides This includes understanding how the "staple" configuration, the choice of amino acids (such as L- or D-amino acids), and overall peptide structure influence binding affinity and cellular activity.Stapledα-helicalpeptidedrug development: A potent dual inhibitor of MDM2 and MDMX forp53-dependent cancer therapy. PNAS USA 110(36):E3445-E3454 (2013) ... The development of these stapled peptides involves a deep understanding of protein-protein interactions and medicinal chemistry.2023年2月26日—Stapled peptidesconsisting of either L- or D-amino acids have been discovered with both classes of molecules binding to Mdm2 and MdmX to ...

In summary, Merck's p53 stapled peptide patent portfolio and ongoing research signify a significant commitment to leveraging stapled peptide technology for cancer treatment. By stabilizing key therapeutic molecules like p53 and targeting its regulators, such as MDM2 and MDMX, Merck is paving the way for a new generation of cancer therapies.Tumor-Targeted Delivery of the p53-Activating Peptide ... The continuous innovation in peptide design, delivery mechanisms, and the exploration of compounds like ALRN-6924 underscore the potential of this field to provide life-saving treatments for patients worldwideWO 2017/136652 A1 - Googleapis.com. The patent landscape in this area, which includes filings like EP3256484A1, is a testament to the robust intellectual property being generated around these groundbreaking therapeutic strategies.