Expert Opinion on Therapeutic Patents最新文献

Introduction: The emergence of drug resistance poses a serious threat to cancer chemotherapy by a single agent. Tumor cell heterogeneity, mutation, and/or desensitization of receptor render monotherapy ineffective. Combination encompassing multiple targets or biochemical pathways seems promising for cancer treatment. Combination of HDAC inhibitor(s) with other inhibitor(s) has shown synergistic activity in cancer chemotherapy by modulating a variety of therapeutic targets including epigenetic target of cancer cells by restoring acetylation and reactivating tumor suppressor genes leading to cell cycle arrest, promoting apoptosis, and thus inhibiting cancer cell proliferation.

Areas covered: A comprehensive published patent literature (2020-present) on rational combinations of HDAC inhibitor(s) for cancer chemotherapy has been retrieved and reviewed from various patent databases including Google Patents, Espacenet, Patentscope, WIPO, and USPTO to analyze the rational combinations for better, optimized, and precise cancer therapy. In this second part of two-part review, we highlighted the patent published for the combination.

Expert opinion: The HDAC inhibitor(s) in combination with other therapeutically relevant inhibitor(s) such as MAPK, GSK3, PI3K/mTOR, PARP, CDK9, HSP90, BTK, BRD4, JAK, VEGF, ALK, PD-1, or PDE inhibitor showed synergistic anti-cancer activity. These combinations not only overcame drug resistance but also acted against relapsed/refractory cancers.

Background: Nuclear receptor related 1 (Nurr1) is a ligand-activated transcription factor and considered as neuroprotective and anti-neuroinflammatory target. Several lines of evidence support potential of Nurr1 modulation in treating neurodegenerative diseases as well as in certain cancers, but potent and selective Nurr1 modulators are rare.

Areas covered: Development of small molecule Nurr1 modulators is gaining momentum which is also reflected in recent patent applications (published between 01/2019 and 09/2024, available on Google Patents). The claimed Nurr1 ligands are derived from the natural ligands prostaglandin A and dihydroxyindole as well as synthetic scaffolds. Their proposed use mainly refers to neurodegenerative disease and cancer treatment.

Expert opinion: Nurr1 modulation is emerging as new therapeutic concept in neurodegeneration and beyond and considerable progress has been made in Nurr1 ligand discovery with several promising compounds covered by patent applications. However, some reported and claimed ligands seem to lack validation and some claims appear very broad without presenting respective examples.

Introduction: Gain-of-function mutations in KCNT1 channels has been associated with severe childhood epilepsies. KCNT1 channels are sodium activated potassium channels in the CNS involved in neuronal excitability. Substantial efforts have been made by several groups to discover novel small molecule KCNT1 inhibitors to validate this approach as a therapeutic strategy for the treatment of KCNT1-related epilepsies.

Areas covered: This review focuses on 10 published international patent applications from Praxis Precision Medicine that disclose novel small molecule KCNT1 inhibitors for the treatment of KCNT1-related neurological disorders. Features of compounds that contribute to KCNT1 inhibition and published in applications between 2022 and 2024 are discussed. Applications were identified and obtained through the online database, Patentscope, provided by the World Intellectual Property Organization (WIPO) using the search term 'KCNT1 inhibitors.'

Expert opinion: Tremendous progress has been made toward the discovery of small molecule inhibitors of KCNT1 channels; however, much work remains to reach a viable therapeutic. Areas of work that will be critically important include further in vivo studies for efficacy, safety, and development of PK/PD relationships. Studies to better understand the binding of known ligands and determine the structural features that govern modulation of the channel are also much needed.

Introduction: Targeting three-dimensional RNA structures with traditional drug-like small molecules is gaining wide attention in both the academia and the pharmaceutical industries, due to their good oral bioavailability, cheap production cost, and the possibility of fine-tuning ADMET properties, which represent a powerful alternative to the current RNA-targeted therapies, including ASO and siRNA. As RNAs are involved in nearly all the physiological and pathological processes, small molecules RNA ligands can have a plethora of different therapeutic applications, spanning from cancer to infectious and neurological diseases.

Areas covered: This review describes patents concerning small molecules RNA ligands published within January 2018 and October 2024, searched through Espacenet, Patentscope, and Google Patents databases.

Expert opinion: The number of patents that has been released in the last few years demonstrates the relevance of targeting RNA structures for the development of next generation chemotherapeutic agents and antiviral/antibacterial drugs, even though this field is still in its infancy and many issues still need to be resolved, in particular related to selectivity. An emerging approach to considerably limiting side effects is presented by RIBOTAC derivatives, as promoting a selective RNase-L mediated RNA degradation allows to significantly reduce the dose of the compound.

Introduction: The collective behavior of bacteria is regulated by Quorum Sensing (QS), in which bacteria release chemical signals and express virulence genes in a cell density-dependent manner. Quorum Sensing inhibitors (QSIs) are a large class of natural and synthetic compounds that have the potential to competitively inhibit the Quorum Sensing (QS) systems of several pathogens blocking their virulence mechanisms. They are considered promising compounds to deal with antimicrobial resistance, providing an opportunity to develop new drugs against these targets.

Areas covered: The present review represents a comprehensive analysis of patents and patent applications available on Espacenet and Google Patent, from 2019 to 2023 referring to the therapeutic use of Quorum Sensing inhibitors.

Expert opinion: Unlike classical antibiotics, which target the basic cellular metabolic processes, QSIs provide a promising alternative to attenuating virulence and pathogenicity without putting selective pressure on bacteria. The general belief is that QSIs pose no or little selective pressure on bacteria since these do not affect their growth. To date, QSIs are seen as the most promising alternative to traditional antibiotics. The next big step in this area of research is its succession to the clinical stage.

Introduction: Signal transducer and activator of transcription 3 (STAT3), a member of the STAT protein family, serves as both a signal transducer and a transcription factor. Previous studies have highlighted its pivotal roles in regulating cell proliferation, differentiation, apoptosis, as well as immune and inflammatory responses. Consequently, targeting STAT3 has emerged as a promising therapeutic strategy for addressing related diseases.

Areas covered: This review offers a comprehensive summary of the progress in discovering STAT3 inhibitors, with a focus on their structural diversity and structure-activity relationships as presented in patent literature from 2022 to the present.

Expert opinion: Over the past decades, significant progress has transformed STAT3 into a target of interest for drug development. Despite these advances, no STAT3-targeting drugs have successfully progressed through late-phase clinical trials, largely due to challenges such as limited selectivity and undesirable side effects. These obstacles highlight the inherent complexity of developing safe and effective STAT3 inhibitors. Nevertheless, STAT3 remains a highly promising therapeutic target, and ongoing advancements in this field hold the potential to unlock novel strategies for addressing STAT3-related diseases.

Introduction: Indoleamine 2,3-dioxygenase 1 (IDO1) is a promising target in cancer immunotherapy, yet its application faces significant challenges due to complex mechanisms of action. Recent advancements in IDO1 inhibitors aim to tackle these issues, potentially paving the way for successful therapeutic development.

Areas covered: This review highlights patent publications (2023-2024) related to IDO1 inhibitors with potential anti-cancer applications, sourced from Espacenet and Google Scholar.

Expert opinion: IDO1 exhibits complex mechanisms of action and variable expression across different cancer types, presenting both challenges and opportunities. Its intricate mechanisms in tumor development and immune evasion pose significant challenges for translating IDO1 inhibitors into clinical drugs. However, recent advancements in AI-guided drug design, combination therapies, and improved drug delivery methods offer promising insights for enhancing IDO1 inhibitors, although further data is warranted. Despite these challenges, the increasing availability of IDO1 crystal structures and a deeper understanding of its biological roles support ongoing trials that combine IDO1 inhibitors with other therapies. These developments hold potential for improving therapeutic outcomes in cancer treatment. Moreover, the growing interest in applying IDO1 inhibitors to other diseases could stimulate further research and development of new IDO1 inhibitors, potentially benefiting their application in cancer therapy as well.

Introduction: The Angiotensin-converting enzyme 2 (ACE2) receptor, crucial for coronavirus recognition of host cells, is a key target for therapeutic intervention against SARS-CoV-2 and related coronaviruses. Therefore, thoroughly investigating the interaction mechanism between ACE2 and the Spike protein (S protein), as well as developing targeted inhibitors based on this mechanism, is vital for effectively controlling the spread of SARS-CoV-2 and preventing potential future pandemics caused by other coronaviruses.

Areas covered: This article comprehensively reviews the mechanisms underlying ACE2-S protein interaction that facilitate SARS-CoV-2 entry into host cells. It also analyzes the patent landscape regarding inhibitors targeting the ACE2-S interface since 2019.

Expert opinion: In the 5 years since the outbreak of SARS-CoV-2, numerous methods and design strategies have been employed to develop innovative therapeutics against coronaviruses. Among these approaches, inhibitors targeting both the ACE2 receptor and the S protein have gained significant interest due to their potential in blocking various coronaviruses. Despite facing challenges similar to other protein-protein interaction inhibitors, progress has been made in developing these inhibitors through virtual screening, covalent protein binding, and peptide modification strategies. However, obstacles persist in clinical translation, necessitating a multidisciplinary strategy that integrates state-of-the-art methodologies to optimize S-ACE2 interface-targeted drug discovery.

Introduction: isocitrate dehydrogenase 1 (IDH1), a key metabolic enzyme in the cytosol, catalyzes the oxidative decarboxylation of isocitrate to produce α-ketoglutarate (α-KG) and NADPH in the TCA cycle. Pan-cancer studies have demonstrated that IDH1 exhibits a higher mutation frequency and is implicated in a broader range of cancer types, indicating its potential as a promising anti-tumor target.

Areas covered: We summarized patents from 2018 to the present that identify novel molecules, compounds, formulations, and methods for inhibiting mIDH1. The literature was retrieved from Web of Science and PubMed. Patent information was obtained via the State Intellectual Property Office's Patent Search and Analysis platform. Clinical data were sourced from the Cortellis Drug Discovery Intelligence database. The date of the most recent search was .

Expert opinion: Due to multiple signaling pathway dysregulations and compensatory pathways in solid tumor, monotherapies targeting mutant IDH1 (mIDH1) often fail to achieve desired therapeutic outcomes. Consequently, the combination of mIDH1 inhibitors with other therapeutic agents can enhance the efficacy of antitumor treatments and mitigate the risk of drug resistance. Moreover, the development of novel dual or multiple inhibitors and functional molecules targeting mIDH1 May represent a more promising approach.

Introduction: The Transcriptional Enhanced Associated Domain (TEAD) family has attracted increasing attention due to its crucial role in the Hippo signaling pathway, which regulates cell growth, division, survival, differentiation, and tissue homeostasis in multicellular organisms. Inhibition of TEADs with small molecules has been shown to be an effective strategy for the treatment of tumors, and several compounds have entered clinical trials as monotherapy and/or combination therapy.

Areas covered: Due to the explosion of patent disclosures on TEAD modulators (inhibitors or degraders) in the last two years, this review focuses on the published patent literature on small molecule inhibitors or degraders of TEAD and their applications from June 2022 to present（March 2025）, as a complementary update to the previous patent review (2018-2022).

Expert opinion: The reported TEAD modulators can be categorized into 4 types: non-covalent inhibitors, covalent inhibitors, protein-protein interaction inhibitors and degraders. Meanwhile, the combination therapy with TEAD inhibitors and other kinases or mutated gene inhibitors has shown promising therapeutic effects in patients with various types of cancer, which has greatly expanded the application field of TEAD inhibitors in disease treatment.