Chen XY, Wang K, Jia J
… +3 more, Kong XT, Li HQ, Tian S
Expert Opin Ther Pat
· 2025 May · PMID 39953647
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INTRODUCTION: P2Y receptor (P2YR) is a G protein-coupled receptor that plays a crucial role in regulating platelet activation and aggregation. P2YR is involved in various processes such as renal fibrosis, cancer, ischemi...INTRODUCTION: P2Y receptor (P2YR) is a G protein-coupled receptor that plays a crucial role in regulating platelet activation and aggregation. P2YR is involved in various processes such as renal fibrosis, cancer, ischemic disease, and related complications, making it an appealing target for therapeutic interventions. Over the past decade, the discovery and development of P2YR antagonists have significantly advanced, offering novel treatment options that improve clinical outcomes. AREAS COVERED: This review covers P2YR antagonists reported in patents issued in the online databases of the World Intellectual Property Organization and the European Patent Office from 2019 to 2024. This review introduces the development of existing antagonists and evaluates the therapeutic potential of these compounds. EXPERT OPINION: Reversible P2YR antagonists offer a potentially safer alternative to the currently dominant irreversible antagonists on the market, as they allow for more controlled platelet inhibition and can reduce the toxicity and adverse effects associated with conventional drugs. Importantly, the integration of computational drug design and molecular docking studies in the discovery and optimization of P2YR antagonists represents a significant advancement in precision medicine. This not only provides valuable structural scaffolds but also stimulates novel ideas for developing promising drugs that are both safe and efficacious.
Devesa I, Fernández-Ballester G, Fernandez-Carvajal A
… +1 more, Ferrer-Montiel A
Expert Opin Ther Pat
· 2025 May · PMID 39952645
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INTRODUCTION: TRPV1, a pivotal therapeutic target for chronic pain and pruritus, has been validated in the pathogenesis of several pathologies from diabetes to cancer. Despite the constellation of chemical structures and...INTRODUCTION: TRPV1, a pivotal therapeutic target for chronic pain and pruritus, has been validated in the pathogenesis of several pathologies from diabetes to cancer. Despite the constellation of chemical structures and strategies, none of these molecules has yet been clinically developed as a new drug application due to safety concerns, particularly in thermoregulation. Thus, clinical development of TRPV1 modulators remains a challenge. AREAS COVERED: This review covers the patent literature on TRPV1 modulators (2019-2024, PubMed, Google Patents, and Espacenet), from orthosteric ligands to innovative compounds of biotechnological origin such as interfering RNAs or antibodies, and dual modulators that can act on TRPV1 and associated proteins in different tissues. EXPERT OPINION: Therapeutic strategies that preferentially act on dysfunctional TRPV1 channels appear essential, along with a superior understanding of the underlying mechanisms affecting changes in core body temperature (CBT). Recent findings describing differential receptor interactions of antagonists that do not affect CBT may pave the way to the next generation of orally active TRPV1 inhibitors. Although we have thus far experienced a bitter feeling in TRPV1 drug development, the recent progress in different disciplines, including human-based preclinical models, will set an interdisciplinary approach to design and develop clinically relevant TRPV1 modulators.
INTRODUCTION: Hematopoietic progenitor cell kinase (HPK1) is a serine/threonine kinase of MAP4K family. It negatively regulates T cell receptor and B cell signal transduction. The loss of HPK1 kinase function increases t...INTRODUCTION: Hematopoietic progenitor cell kinase (HPK1) is a serine/threonine kinase of MAP4K family. It negatively regulates T cell receptor and B cell signal transduction. The loss of HPK1 kinase function increases the secretion of cytokines and enhances T cell signal transduction, virus clearance and tumor growth inhibition. Therefore, HPK1 is considered as a promising drug target for tumor immunotherapy. AREA COVERED: This article surveys the patents published since 2021 aiming to analyze the structural features of scaffolds and the patent landscape. It also discusses the recent clinical developments and provides perspectives on the challenges and the future directions. EXPERT OPINION: HPK1 kinase is a viable drug target, and there is an increasing number of clinical studies on HPK1 inhibitors. In the clinical research of HPK1 inhibitors, there are mainly two ways: monotherapy and combination therapy. In recent years, HPK1 degraders derived from PROTAC technology have shown promises along with HPK1 inhibitors. It is hopeful that small molecule inhibitors or degraders targeting HPK1 will gain FDA approval for treatment of human diseases in the near future. DATABASES SEARCHED AND INCLUSIVE DATES: A rapid survey of literature reports using keyword 'HPK1' in SciFinder® search engine yielded about 180 papers since 2021.
Expert Opin Ther Pat
· 2025 May · PMID 39948693
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INTRODUCTION: Metabotropic glutamate receptor 4 (mGluR4) regulates disease by modulating neurotransmitter release and synaptic plasticity and has been implicated in various diseases, including neurodegenerative disorders...INTRODUCTION: Metabotropic glutamate receptor 4 (mGluR4) regulates disease by modulating neurotransmitter release and synaptic plasticity and has been implicated in various diseases, including neurodegenerative disorders and psychiatric conditions, where its dysregulation can impact synaptic function and neuronal signaling. AREAS COVERED: This review covers the patents and key literature concerning mGluR4 PAMs by utilizing the search engines: SciFinder, Google Patents, and PubMed from 2017 to 2024. It summarizes the key exemplified compounds, relevant SAR, and key biological data presented in the patents and primary literature. The key findings and potential path forward are also discussed. EXPERT OPINION: The mGluR4 receptor serves as a novel target for the treatment of neurodegenerative disorders (namely Parkinson's disease), multiple sclerosis, and chronic pain along with other brain disorders. Two compounds have been advanced to early-stage clinical trials from Prexton Therapeutics and Appello Pharmaceuticals. The first compound from Prexton failed due to efficacy and the Appello compound has yet to have results disclosed. The results from this trial will be an important test for whether future mGluR4 PAMs are advanced into clinical trials.
INTRODUCTION: The chemokine receptor CXCR4 has been under intense study due to the central role it plays in immune system regulation and the pathology of human disease. Although the first CXCR4 drug plerixafor emerged ov...INTRODUCTION: The chemokine receptor CXCR4 has been under intense study due to the central role it plays in immune system regulation and the pathology of human disease. Although the first CXCR4 drug plerixafor emerged over a decade ago (2007), recently the first peptide (motixafortide, 2023) and the first oral small molecule (mavorixafor, 2024) CXCR4 antagonists became FDA approved. AREAS COVERED: This article describes patent documents published during the period of 2019 through 2024 for both small molecule and peptides. This IP includes few new chemotypes, with most being extensions of existing structural classes. There is also less significant IP covering peptide-based therapeutics than those covering small molecules. Notably, multiple therapeutic uses have also emerged. Patents were searched from SciFinder (CAS) and Google Patents with the term . Patents were selected according to whether they fit into the classification of small molecules or peptides. EXPERT OPINION: In the last 5 years there has been significant advancement in CXCR4 antagonists as gauged by the FDA approval of two drugs. The search for second and third generation compounds will be the focus of future efforts with new uses and better properties which likely could come from some of the IP described herein.
INTRODUCTION: Bromodomain-containing protein 4 (BRD4) stands as a pivotal member within the Bromodomain and Extra-Terminal Domain (BET) family, contributing significantly to epigenetic control and gene expression. Given...INTRODUCTION: Bromodomain-containing protein 4 (BRD4) stands as a pivotal member within the Bromodomain and Extra-Terminal Domain (BET) family, contributing significantly to epigenetic control and gene expression. Given its association with various cancers, BRD4 emerges as a promising therapeutic target, suggesting a substantial role in the treatment of diverse pathological conditions. AREAS COVERED: The present review is centered on patent applications concerning inhibitors targeting BRD4's bromodomain site, published from 2020 to present. A comprehensive evaluation was conducted on a total of 70 applications. The latest patented studies of BRD4 are summarized by using the keywords 'BRD4' in SciFinder, PubMed, and The lens Patents and databases in the year from 2020 to present. EXPERT OPINION: Despite the substantial progress achieved in the clinical research of numerous BET bromodomain inhibitors, their development remains fraught with challenges. To mitigate the dose-limiting toxicity (DLT) and other clinical adverse effects associated with pan-BET inhibitors, current research efforts are increasingly focus on the development of selective BRD4-BD1 or -BD2 inhibitors. These selective inhibitors exhibit considerable potential as more efficacious candidate drugs, thereby paving the way for novel avenues in both fundamental and translational research within this domain.
INTRODUCTION: Kelch-like ECH-associated protein 1 (Keap1), an E3 ligase negatively regulating the nuclear factor erythroid 2-related factor 2 (Nrf2), has emerged as an auspicious drug target for treating ailments associa...INTRODUCTION: Kelch-like ECH-associated protein 1 (Keap1), an E3 ligase negatively regulating the nuclear factor erythroid 2-related factor 2 (Nrf2), has emerged as an auspicious drug target for treating ailments associated with oxidative stress and inflammation. Discovery of Keap1 inhibitors have attracted significant interest. AREAS COVERED: This review covers patents on Keap1 inhibitors from 2019 to 2024, providing a comprehensive analysis of their structural characteristics, optimization strategies, pharmacological properties and clinical progress. EXPERT OPINION: Extensive efforts have been devoted to enhance potency and drug-like properties of Keap1 inhibitors. Strategies such as ROS-cleavable prodrug design, bivalent inhibition and PROTACs are emerging. As the range of drug types and applications expands, Keap1 inhibitors are becoming a sagacious option for disease treating.
INTRODUCTION: Targeting immune checkpoint proteins (ICPs) via small molecules open a new window for cancer immunotherapy. Herein, we summarize recent advances of small molecules with novel chemical structures targeting I...INTRODUCTION: Targeting immune checkpoint proteins (ICPs) via small molecules open a new window for cancer immunotherapy. Herein, we summarize recent advances of small molecules with novel chemical structures targeting ICPs, discusses their anti-tumor efficacies, which are important for the development of novel small molecules for cancer immunotherapy. AREAS COVERED: In this review, the latest patents and literature were gathered through the comprehensive searches in the databases of European Patent Office (EPO), Cortellis Drug Discovery Intelligence (CDDI), PubMed and Web of Science using ICPs and compounds as key words. EXPERT OPINION: To develop novel weapons to fight against cancer, small molecules targeting ICPs including CTLA-4, LAG-3, PD-L1, Siglec-9, TIM-3, TIGIT, and VISTA have been synthesized and evaluated in succession. Chief among them are the small molecules targeting PD-L1, which have been intensively investigated in recent years. Various in vitro assays such as ALPHA, HTRF binding assay, NFAT assay have been successfully developed to screen novel IPCs inhibitors. However, the in vivo assay, for example, using double-humanized PD-1/PD-L1 (hPD-1/hPD-L1) mouse as evaluation model, are seldom reported. Novel pharmacophores with new working mechanisms such as proteolysis targeting chimeras (PROTACs) and peptides are needed to enhance the therapeutic efficacy.
Urbina A, Hallatt AJ, Robertson J
… +1 more, Ciulli A
Expert Opin Ther Pat
· 2025 Feb · PMID 39834300
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INTRODUCTION: The von Hippel-Lindau (VHL) E3 ubiquitin ligase has seen extensive research due to its involvement in the ubiquitin proteasome system and role as a tumor suppressor within the hypoxia signaling pathway. VHL...INTRODUCTION: The von Hippel-Lindau (VHL) E3 ubiquitin ligase has seen extensive research due to its involvement in the ubiquitin proteasome system and role as a tumor suppressor within the hypoxia signaling pathway. VHL has become an attractive target for proteolysis targeting chimeras (PROTACs), bifunctional molecules that can induce degradation of neo-substrate proteins. The development of VHL inhibitors and PROTACs has seen rapid development since disclosure of the first non-peptidic VHL ligand (2012). AREAS COVERED: Due to the demand for more diverse and sophisticated VHL ligands that can be applied to PROTACs, the number of patents disclosed has risen significantly in the past 5 years. Herein, the wide range of VHL modifications that have been patented since 2019 is covered. Specifically, any new or unique chemical modification to established VHL ligands or PROTACs will be discussed. EXPERT OPINION: The VHL chemical space continues to expand within the patent literature. There are exciting new modifications that can enhance the physiochemical properties of VHL PROTACs and other alterations can improve the affinity of the VHL ligand itself. Further optimization of the VHL chemical space will no doubt lead to the development of more VHL-based therapies and clinical candidates.
Expert Opin Ther Pat
· 2025 Feb · PMID 39816001
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INTRODUCTION: Opioids have served as a cornerstone in pain management for decades. However, the emergence of increasingly potent synthetic analogs brings forth a range of side effects, including respiratory depression, t...INTRODUCTION: Opioids have served as a cornerstone in pain management for decades. However, the emergence of increasingly potent synthetic analogs brings forth a range of side effects, including respiratory depression, tolerance, dependence, constipation, and, more importantly, the development of severe and debilitating opioid use disorder (OUD). Search for therapeutics to mitigate OUD has been challenging, and this has called for novel approaches that include the design of small molecules targeting neuronal circuits involved in addiction (opioid, dopamine, serotonin, norepinephrine, and glutamate receptors, etc.). AREAS COVERED: In this review, we retrieve and discuss two dozen (24) relevant patents filed in the past six (6) years that focus on novel small-molecule therapeutics for OUD. The chemical entities disclosed were highlighted, and specific examples were provided where necessary. EXPERT OPINION: Several chemical entities targeting both opioid and non-opioid targets are under consideration for treating OUD. Our search for patents covering such compounds revealed embodiments with diverse chemistry. Understanding the public impact of OUD and the rapidly evolving landscape of substance abuse underscores the urgent need for a thorough reevaluation of strategies to address these challenges. This includes the development of small molecules with unique mechanisms of action for OUD treatment.
Expert Opin Ther Pat
· 2025 Jan · PMID 39757430
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INTRODUCTION: Histamine H receptor antagonists/inverse agonists, since the discovery of histamine H receptor (HR), are important ligands in the search for new potential drugs. The most interesting are CNS diseases as the...INTRODUCTION: Histamine H receptor antagonists/inverse agonists, since the discovery of histamine H receptor (HR), are important ligands in the search for new potential drugs. The most interesting are CNS diseases as these receptors are mainly there present. AREAS COVERED: The current review covers patent applications/patents that were published during the last 6 years (October 2017 - December 2023). Documents were found in two free available patent databases: Espacenet and PatentScope and divided into three basic categories such as methods, compounds, and therapeutic indications. It provides an overview of 51 patent applications/patents. Many pharmaceutical compositions with HR antagonists/inverse agonists have been claimed. Furthermore, PubMed, Scopus, and ClinicalTrials databases were searched for literature to prepare this review. EXPERT OPINION: Interest in the HR field is still high and has remained almost unchanged over the last 10 years in the number of publications, but the type of publications has changed (fewer new ligands, more pharmacological studies). Currently, the search for new HR ligands is focused on multi-target compounds. The first crystal structure of HR with a ligand appeared. New therapeutic indications, such as autism, fatigue, and Prader-Willi syndrome, are verified in clinical trials.
Liu C, Mao Q, Zhang B
… +3 more, Fu X, Zhang T, Wang S
Expert Opin Ther Pat
· 2025 Feb · PMID 39731464
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INTRODUCTION: Xanthine oxidase (XO) catalyzes the oxidation of both hypoxanthine and xanthine in the last two steps of the purine metabolic pathway, serving as a rate-limiting enzyme for uric acid production as well as a...INTRODUCTION: Xanthine oxidase (XO) catalyzes the oxidation of both hypoxanthine and xanthine in the last two steps of the purine metabolic pathway, serving as a rate-limiting enzyme for uric acid production as well as a key target for the treatment of gout and other hyperuricemia-related conditions. AREAS COVERED: This paper reviews XO inhibitors in patents from 2021 to the present. We summarize in detail the structural classes and characteristics, in vitro and in vivo biological results, and structure‒activity relationships of synthetic inhibitors, as well as the sources, specific structures, research methods, and biological activities of XO inhibitors from natural products. EXPERT OPINION: (1) Benefiting from the discovery of many high-affinity inhibitors, the binding modes of small molecules in the active pocket of XO have been further elucidated, and this information will contribute to future development; (2) natural products remain one of the important sources in the discovery of XO inhibitors; (3) with a deeper exploration of XO and URAT1 targets, XO/URAT1 dual target inhibitors may be a future research hotspot; and (4) the search for high-affinity, small-molecule scaffolds remains a key challenge and an important direction for the future development.
Ivanenkov YA, Malyshev AS, Terentiev VA
… +6 more, Korzhenevskaya AA, Evteev SA, Vatsadze SZ, Medved'ko AV, Shegai PV, Kaprin AD
Expert Opin Ther Pat
· 2025 Feb · PMID 39727182
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INTRODUCTION: The ataxia telangiectasia mutated kinase (ATM) is key in coordinating the DDR signaling network essential for responding to double-strand breaks (DSBs). Several ATM inhibitors are being investigated for pot...INTRODUCTION: The ataxia telangiectasia mutated kinase (ATM) is key in coordinating the DDR signaling network essential for responding to double-strand breaks (DSBs). Several ATM inhibitors are being investigated for potential anticancer treatment in clinical trials. AREAS COVERED: This review aims to provide a comprehensive overview of patents and patent applications since 2003, with a particular focus on the structural properties, activity and efficacy of the claimed ATM kinase small-molecule inhibitors. The search was conducted using SciFinder, Cortellis Drug Discovery Intelligence Database, and Espacenet. After filtering, 44 records were identified for further analysis. This paper also discusses the recent progress in the clinical trials and development history. EXPERT OPINION: ATM kinase is a promising target for cancer therapy. Small-molecule ATM kinase inhibitors hold significant potential in cancer treatment by enhancing the efficacy of existing DNA-damaging therapies. Patent analysis revealed that the majority of these compounds contain imidazo[4,5-c]quinolinone scaffold or its bioisosteric variations which are optimal in terms of good ATM inhibitory activity and selectivity over closely related enzymes. Clinical trials explore combinations with RT or DNA-targeted compounds like PARP inhibitors, which induce DSBs. The medicinal chemistry field anticipates that these therapeutic options will soon be available on the pharmaceutical market.
Expert Opin Ther Pat
· 2024 Dec · PMID 39721070
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INTRODUCTION: Methyltransferase-like protein 3 (METTL3), in complex with METTL14, is the key 'writer' protein for RNA mA methylation, accounting for almost all mRNA mA modifications. Recent studies reveal that METTL3 is...INTRODUCTION: Methyltransferase-like protein 3 (METTL3), in complex with METTL14, is the key 'writer' protein for RNA mA methylation, accounting for almost all mRNA mA modifications. Recent studies reveal that METTL3 is implicated in the development and progression of various types of cancers. Targeting METTL3 with small molecule inhibitors represents a promising therapeutic strategy for cancer. AREAS COVERED: This review provides an overview of the patent literature covering METTL3 inhibitors. A literature search was conducted in SciFinder by using 'METTL3 inhibitor' as a keyword and was refined by narrowing the criteria to patents. EXPERT OPINION: Efforts to develop METTL3/METTL14 inhibitors have led to the advancement of the drug candidate STC-15 to clinical trials. Preclinical studies of STC-15 show promise in inhibiting tumor growth via direct anti-tumor effects and anti-cancer immune responses. The clinical trial outcomes of STC-15 will shape future METTL3/METTL14 inhibitor development. However, critical questions remain. The role of METTL3/METTL14 in mA RNA methylation is essential for cellular activity, raising concerns about the potential adverse effects of targeting this complex. Furthermore, depending on the context, METTL3/METTL14 can function as a tumor suppressor. This underscores the need for a deeper understanding of the molecular mechanisms by which RNA modifications regulate cancer.
Gorecki L, Reznickova E, Krystof V
… +3 more, Rezacova M, Ceckova M, Korabecny J
Expert Opin Ther Pat
· 2025 Feb · PMID 39718422
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INTRODUCTION: Approximately one-third of all AML patients have a mutation in the () gene, which is associated with a poor prognosis in these individuals. The 2017 approval of midostaurin, the first FLT3 inhibitor, spurr...INTRODUCTION: Approximately one-third of all AML patients have a mutation in the () gene, which is associated with a poor prognosis in these individuals. The 2017 approval of midostaurin, the first FLT3 inhibitor, spurred extensive development of more potent and selective inhibitors with an improved safety profile. AREAS COVERED: This review analyzes patent inventions for the treatment of AML using FLT3 inhibitors, covering developments from the earliest to the most recent, disclosed in 2024. Our search using the global Espacenet database identified numerous compounds with low nanomolar inhibitory concentrations against FLT3-ITD and FLT3-TKD mutants. These compounds have shown promise in preclinical studies. Co-inhibition strategies and combinatorial therapies to overcome resistance and enhance anti-leukemic efficacy are also discussed. EXPERT OPINION: Recent patents highlight advances in the field of FLT3 inhibitors with a focus on overcoming resistance, improving selectivity and potency. Future strategies may include third-generation inhibitors such as type III allosteric inhibitors, irreversible inhibitors, or PROTACs. Personalized medicine approaches utilizing genetic profiling to tailor therapies are emphasized. Exploration of novel combination regimens with emerging therapies like CAR T-cell therapy, immune checkpoint inhibitors, and small molecules targeting critical AML pathways is ongoing to further enhance anti-leukemic efficacy.
Expert Opin Ther Pat
· 2024 Dec · PMID 39717968
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INTRODUCTION: Neuroinflammation is correlated to neurodegenerative diseases like Alzheimer's disease (AD), Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), Huntington Disease (HD), and Parkinson's disease (P...INTRODUCTION: Neuroinflammation is correlated to neurodegenerative diseases like Alzheimer's disease (AD), Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), Huntington Disease (HD), and Parkinson's disease (PD). A lot of recent research and patents are focused on the design and synthesis of arachidonic acid lipoxygenase (ALOX) inhibitors for the treatment of neurodegenerative diseases. AREAS COVERED: The survey covers natural products, synthesis, hybrids, and assessments of biological effects in biological studies as ALOX inhibitors. A survey of patent publications from 2018 to present, taken from Google Scholar, Espanet, Web of Science, Drugbank, Scopus, or PubMed is analyzed. EXPERT OPINION: The authors suggest that (i) numerous areas of biology-pharmacology need to be considered: selectivity, in vivo studies, toxicity, bioavailability, and drug-likeness, the mechanism of action in different animals and humans, evaluation of more efficient and selective biological tests; (ii) synthetic method outbalance in the discovery and production of ALOX inhibitors with greater selectivity. Several ALOX inhibitors show promising results for the treatment of neurological disorders. Their clinical evaluation will be critical to assess therapeutic utility. The compounds for which the mechanism of action and their bioavailability are well defined can be used as lead compounds for the treatment of neurodegenerative diseases.
Gao Y, Lan L, Wang C
… +3 more, Wang Y, Shi L, Sun L
Expert Opin Ther Pat
· 2025 Feb · PMID 39716925
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INTRODUCTION: The family of Janus kinases (JAKs) consists of four intracellular non-receptor tyrosine kinases: JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2). Among these four subtypes, JAK1 is the only isoform that can...INTRODUCTION: The family of Janus kinases (JAKs) consists of four intracellular non-receptor tyrosine kinases: JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2). Among these four subtypes, JAK1 is the only isoform that can form heterodimers with all three JAKs, and JAK1 dysfunction can lead to inflammation and severe autoimmune diseases. Interest in JAK1 inhibitors has grown tremendously, and the number of inhibitors targeting JAK1 continues to rise annually. AREAS COVERED: This paper reviews JAK1 small molecule inhibitors that were reported in patent literature from January 2016 to December 2023. Web of Science, SciFinder, PubMed, WIPO, EPO, USPTO, and CNIPA databases were used for searching the literature and patents for JAK1 inhibitors. EXPERT OPINION: JAK1 inhibitors show great promise in treating cytokine dysregulated disorders; nevertheless, nonselective JAK1 inhibitors have more severe side effects, which restricts the therapy's safety and use. Therefore, developing highly selective JAK1 inhibitors can mitigate potential risks and lead to next-generation therapies with improved efficacy and safety profiles.
Expert Opin Ther Pat
· 2025 Feb · PMID 39708287
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INTRODUCTION: Mutations in epidermal growth factor receptor (EGFR) kinase domain consistently activate downstream signaling pathways, such as the PI3K/AKT/mTOR and RAS/RAF/MEK, thereby promoting tumor growth. Although th...INTRODUCTION: Mutations in epidermal growth factor receptor (EGFR) kinase domain consistently activate downstream signaling pathways, such as the PI3K/AKT/mTOR and RAS/RAF/MEK, thereby promoting tumor growth. Although the majority of non-small cell lung cancer (NSCLC) patients harboring EGFR mutations are sensitive to existing EGFR tyrosine kinase inhibitors (EGFR-TKIs), there remains an unmet clinical need for effective therapies targeting EGFR Ex20ins mutations, making direct targeting EGFR Ex20ins mutations a promising therapeutic strategy. AREAS COVERED: This review covers the progress of clinical studies targeting EGFR Ex20ins inhibitors and summarizes recent (1 January 2019 - 30 April 2024) patents disclosing EGFR Ex20ins inhibitors available in the Espacenet and CAS SciFinder databases. EXPERT OPINION: An increasing number of EGFR Ex20ins inhibitors are being developed and reported. Existing inhibitors are focused on enhancing the efficacy of EGFR Ex20ins inhibitors and addressing the challenge of targeted resistance by optimizing the second - or third-generation EGFR inhibitors and developing innovative skeleton molecules. Moreover, the development of targeted protein degraders, allosteric inhibitors, and combination therapies provide additional approaches to address EGFR Ex20ins mutations. However, bypass resistance, selectivity, and drug sensitivity still pose challenges in this field.
Expert Opin Ther Pat
· 2024 Dec · PMID 39708134
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INTRODUCTION: The mitogen-activated protein kinase interacting kinases (MNKs) modulate protein translation through the phosphorylation of eukaryotic initiation factor 4E (eIF4E) at serine 209, which is crucial for tumori...INTRODUCTION: The mitogen-activated protein kinase interacting kinases (MNKs) modulate protein translation through the phosphorylation of eukaryotic initiation factor 4E (eIF4E) at serine 209, which is crucial for tumorigenesis but dispensable for normal development. MNKs are implicated in various pathological processes, including inflammation, obesity, cancer, etc. Thus, MNKs are considered as potential drug targets and the development of potent and selective MNK inhibitors is a current research focus. AREAS COVERED: This review covers inhibitors of MNKs reported in patents published in the online databases of the World Intellectual Property Organization and European Patent Office from 2019 to 2024. This review provides a landscape of available inhibitors, including their chemical structures, activity, and stage of development. EXPERT OPINION: In recent years, highly potent and selective inhibitors have been discovered and many of them show promising results in several preclinical cancer models. The majority of small-molecule inhibitors developed recently, similarly to the structure of eFT508 and ETC-206. Also, some new skeletons were disclosed and showed novel mechanisms, including non-traditional ATP competition and induced protein degradation by proteolysis targeting chimeras. Ongoing preclinical research and clinical trials will provide us more information on these new compounds and MNKs novel functions beyond cancer.