INTRODUCTION:Poly(ADP-ribose) polymerase 1 (PARP1) is a key mediator of DNA damage repair and an attractive therapeutic target for homologous recombination-deficient malignancies. The development of selective PARP1 inhibitors has been driven by the need to reduce the hematological toxicities associated with nonselective PARP inhibition. AREA COVERED:This review summarizes patents and recent advances in selective PARP1 inhibitors reported from 2021 to the present. Particular emphasis is placed on the structural evolution of AZD5305-derived compounds and emerging quinazolinone- and isoquinolinone-based chemotypes. Key design strategies, including adenine-pocket optimization, linker remodeling, conformational restriction, and scaffold diversification, are discussed together with their impact on PARP1 selectivity and biological activity. EXPERT OPINION:Selective PARP1 inhibition has become a major focus of innovation in the PARP field. Current patents indicate that adenine-pocket engagement, linker optimization, conformational control, and scaffold innovation are central to achieving high PARP1 selectivity and represent important directions for future intellectual property development. Despite significant progress, the disclosed chemical space remains relatively limited, highlighting opportunities for further scaffold diversification and differentiated patent strategies. These advances are expected to facilitate the development of next-generation PARP1-targeted therapeutics with improved safety profiles and broader clinical potential.
INTRODUCTION:Signal Transducer and Activator of Transcription 6 (STAT6) is a critical transcription factor in the interleukin-4 (IL-4) and IL-13 signaling pathways and serves as a key pathogenic driver of type 2 (TH2) immune responses. Dysregulated STAT6 activity is implicated in asthma, atopic dermatitis, autoimmune diseases, eosinophilic disorders, and certain cancers. As such, targeting STAT6 presents a promising therapeutic strategy for these diseases. AREAS COVERED:This review provides a comprehensive analysis of patent strategies for targeting STAT6 from 2020 to the present. We categorize and evaluate chemical entities based on their core structural features, highlighting key motifs, major patent assignees, and the progression of lead candidates through preclinical and clinical development. EXPERT OPINION:Recent advances reflect a clear evolution from broad JAK/STAT pathway inhibitors toward highly selective STAT6-targeted agents. Although research and development in this area are progressing rapidly with significant achievements, key challenges remain - including optimizing pharmacokinetic properties, achieving tissue specificity, and mitigating off-target effects. The emergence of bifunctional degraders, such as PROTACs, represents a promising frontier for achieving complete and sustained pathway suppression. Future success will likely depend on combining innovative chemistry with sophisticated patient stratification biomarkers to translate potent STAT6 inhibition into safe, effective therapies.
INTRODUCTION:T-type calcium channels are critical for a number of physiological and pathophysiological processes and are potential molecular targets for antiepileptics, analgesics, and drugs that alleviate essential tremor. There have been extensive efforts in identifying and developing novel small organic compounds that block the activities of T-type calcium channels. This is reflected in a number of patent applications and issued patents that cover such molecules. AREAS COVERED:Literature and patent databases (PubMed, Scopus, WoS, USPTO, EPO, SciFinder, Lens, Patentscope, Google Patents, Freepatentsonline) were searched from 2018 to 2025. This review updates the landscape of T-type calcium channel blockers focusing on patented organic small molecules categorized by chemical scaffold. EXPERT OPINION:Multiple molecules that target T-type calcium channels have been tested in preclinical models, and some have recently advanced into the clinic. Adverse effects of pan‑T-type calcium channel blockers that have been reported in clinical trials for essential tremors may perhaps be avoided by the development of T-type channel subtype-specific inhibitors.
INTRODUCTION:Autotaxin (ATX) inhibition has attracted considerable interest as a therapeutic strategy, resulting in more than 50 patents being published by various institutions over the past five years. Consequently, a review of these patented compounds and related research progress could facilitate the discovery of novel ATX inhibitors. AREAS COVERED:This review summarizes ATX inhibitors disclosed in patents from September 2020 to Jan 2026, identified from Espacenet and SciFinder using keyword 'Autotaxin,' and highlights structural features and biological activities in vitro and in vivo. EXPERT OPINION:Currently, beyond the Phase II candidates PAT409 and HW021199, ATX inhibitors FTP-198 and HNC1058 have entered Phase I clinical trials for pulmonary fibrosis, while IOA-289 and HNC664 have advanced to clinical studies for solid tumors, underscoring the immense therapeutic potential of ATX. Although the identification of type V and VI ATX inhibitors has broadened the design landscape, most emerging entities since 2020 remain analogs of GLPG1690 and PAT409, presumably being attributed to the unavailable data of most clinical candidates, and despite the absence of approved drugs, the continued evolution of drug design strategies and application of novel technologies would further facilitate the discovery of ATX candidates, ultimately offering more therapeutic options for patients.
INTRODUCTION:Aldo-keto reductase 1C3 (AKR1C3) is a drug target for the treatment of various androgen‑dependent malignancies, including castration-resistant prostate cancer as well as hematological cancers. The enzyme plays a key role in the conversion of androgen precursors into potent androgen receptor ligands and the conversion of prostaglandins from pro-differential to pro-proliferative, thereby facilitating the progression of these malignancies. Additionally, AKR1C3 plays a role in chemotherapy resistance, reducing therapeutics to inactive forms and stabilizing the expression of mutant androgen receptors. AREA COVERED:This article reviews patents published since 2020, obtained from WIPO and SciFinder, covering AKR1C3 inhibitors, compounds that exploit AKR1C3 for prodrug activation, and the use of AKR1C3 expression levels as a biomarker for measuring disease and therapeutic response. In addition to inhibitors, this article reviews the first reported AKR1C3/AR-v7 dual degrader. EXPERT OPINION:Multiple compounds have been reported to potently and selectively inhibit AKR1C3, eliciting tumor growth inhibition as standalone agents and when used in combination with clinically approved chemotherapeutics. With drug resistance an ever-present issue, exploration of alternative routes for treating malignancies via AKR1C3 targeting offers tremendous potential. Translation to clinical trials and their effect in patients is expected to be revealed in the coming years.
INTRODUCTION:Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a conserved CMGC serine/threonine kinase with an autophosphorylation-dependent activation mechanism. As a dosage-sensitive regulator of transcription, RNA splicing, cell-cycle progression, and signaling, DYRK1A is implicated in neurological, oncological, cardiovascular, metabolic, immune, and infectious diseases. These roles have driven drug discovery, from early probes to advanced clinical-stage inhibitors. AREAS COVERED:This review covers patent literature related to the discovery of DYRK1A inhibitors and degraders published from January 2020 to the review cutoff date. The literature search was conducted in WIPO, Reaxys, SciFinder, Lens.org, Espacenet, USPTO, and Google Patents. EXPERT OPINION:Recent patents indicate that DYRK1A inhibition is no longer a single pharmacological concept but an indication-driven strategy shaped by tissue access, delivery, and mechanistic pharmacodynamic biomarkers. The most credible programs prioritize functional pathway modulation and meaningful target engagement at therapeutically achievable exposure rather than maximal biochemical potency alone, with selectivity defined by disease biology rather than as an absolute requirement. Delivery-advantaged indications such as osteoarthritis and peripheral inflammatory disorders may provide the earliest clinical validation, whereas CNS programs will require brain-penetrant compounds with controlled, likely partial, target modulation. Degraders and macrocycles broaden the toolbox, but biomarker-guided translation remains the key determinant of success.
INTRODUCTION:Takeda G-protein-coupled receptor 5 (TGR5) and farnesoid X receptor (FXR) are bile acid-activated receptors involved in glucose, lipid, and energy homeostasis, making them promising therapeutic targets for type 2 diabetes mellitus (T2DM) and metabolic liver diseases. AREAS COVERED:This review critically analyzes patents published between 2015 and 2025 retrieved from WIPO Patentscope, Espacenet, USPTO, and Google Patents using keyword- and IPC-based strategies. Major patented chemotypes include modified bile acids, benzoic acid-cholane hybrids, heteroaryl scaffolds, and sulfonylurea/sulfonamide derivatives. Several compounds demonstrated sub micromolar (µM) to nanomolar (nM) TGR5/FXR agonistic activity, while gut-restricted agonists showed enhanced GLP-1 secretion with reduced systemic adverse effects such as gallbladder filling and pruritus. Comparative patent analysis revealed a progressive transition from classical steroidal scaffolds toward tissue-selective and gut-restricted modulators designed to improve receptor selectivity, pharmacokinetics, and translational safety. EXPERT OPINION:Despite strong preclinical promise, the clinical translation of TGR5 and FXR agonists remains limited by mechanism-driven toxicities and inadequate long-term tolerability. Future progress will likely depend on tissue-selective, pathway-biased, and gut-restricted modulation rather than further increases in receptor potency.
INTRODUCTION:GPR84 is a pro‑inflammatory, metabolite‑sensing Class A GPCR implicated in a range of inflammatory, fibrotic, metabolic, and neuropathic processes. Its inducible expression and role in amplifying innate immune responses have driven sustained interest in GPR84 antagonists as potential therapeutic agents. AREAS COVERED:This review summarizes recent advances in GPR84 antagonist discovery, focusing on patent applications and research articles retrieved from SciFinder covering 2020 to January 2026. EXPERT OPINION:Recent work and patent filings reflect continued diversification of GPR84 antagonist chemotypes, but the translational outlook remains constrained by biological uncertainty and limited clinical validation. With only a small number of candidatest-such as BAY‑3178275 and BGT‑004-currently in active development, further progress will require deeper mechanistic understanding and clearer definition of disease contexts in which GPR84 modulation may offer therapeutic benefit.
INTRODUCTION:The SLIT2-ROBO signaling axis plays a context-dependent role in cancer, functioning as either a tumor suppressor or oncogenic driver. This bidirectionality creates both therapeutic opportunity and significant challenges for drug development and patent strategy. AREAS COVERED:This review analyzes patents targeting SLIT2-ROBO axis inhibition in cancer from 2020 to 2026. Patent families were retrieved from Google Patents, Espacenet, and WIPO PATENTSCOPE, consolidated by INPADOC family, and evaluated for mechanistic relevance and experimental enablement. Therapeutic modalities include antagonistic antibodies, ligand traps, small molecule and macrocyclic PPI disruptors, nucleic-acid approaches, and bispecific constructs. Each family was assessed using an enablement framework and a directionality-risk checklist, with emphasis on biomarker gating and translational feasibility. EXPERT OPINION:The current patent landscape is limited by the lack of biomarker-driven stratification and incomplete enablement. Future progress will depend on integrating robust assay-to-asset pipelines with biomarker-guided deployment strategies to ensure both clinical efficacy and durable intellectual property.
INTRODUCTION:Selective glucocorticoid receptor modulators (SGRM) have emerged as promising agents to counteract glucocorticoid‑driven chemoresistance, immune suppression, and poor prognosis in solid tumors by modulating glucocorticoid receptor (GR) signaling without losing anticancer immune activity. AREAS COVERED:This review provides a focused update to a previous patent review on SGRM (2014-2020) by summarizing Espacenet-indexed patent applications published between 2020 and 30 April 2026 (PCT/US2020/055498, PCT/US2021/017259, PCT/US2022/042475) describing anticancer strategies. EXPERT OPINION:Collectively, these patents support SGRM in addition to cytotoxic and immunotherapeutic regimens in solid tumors. Preclinical and early‑phase clinical evidence (phase I/II) describes how GR antagonism, continuously or intermittently, lowers elevated neutrophil-to-lymphocyte ratio (NLR), modulates GR‑target transcriptional signatures, and enhances responses to nab‑paclitaxel and anti‑PD‑1 antibodies. Key limitations of these patents consist of evidence based on still limited clinical sample sizes, requiring confirmation in phase III trials, and on benefit enriched in biologically defined subpopulations. From a clinical perspective, these agents could be realistically integrated into anticancer protocols, as they work synergistically with other chemotherapeutics.
INTRODUCTION:As a unique collagen-activated receptor tyrosine kinase, discoidin domain receptor 1 (DDR1) mediates signaling essential for cell proliferation, survival, adhesion, and matrix remodeling. Conversely, its dysregulation is implicated in cancer, tissue fibrosis, atherosclerosis, and other inflammatory diseases. Emerging research reveals that the non-catalytic functions of DDR1 are critically involved in tumor progression, metastasis, and immune exclusion. Selectively inhibiting the catalytic and/or non-catalytic functions of DDR1 presents a promising therapeutic strategy for various diseases. AREAS COVERED:This article summarizes current progress on the development of inhibitors, degraders and biomolecules targeting DDR1 and their potential therapeutic application during the period from 2020 to 2025. EXPERT OPINION:Significant efforts have been made to develop small-molecule DDR1 kinase inhibitors, yet achieving high selectivity remains a challenge. Degraders have been developed to inhibit both its catalytic and noncatalytic functions. Although these molecules offer conceptual advantages over traditional kinase inhibitors, they suffer from suboptimal pharmacokinetic properties. Alternatively, biologics such as antibodies and peptides can block the DDR1-collagen interaction, specifically inhibiting non-catalytic signaling, and one antibody is currently under clinical evaluation. Moving forward, the development of highly selective inhibitors and improvement of pharmacokinetic profiles for degraders will be pivotal for translating DDR1 targeting into viable therapies.
INTRODUCTION:PKMYT1, a member of the WEE family of kinases that regulates mitotic entry by phosphorylating CDK1 at Thr14, has recently gained prominence as a promising synthetic lethal target for oncology. Since the first-in-class PKMYT1 inhibitor entered clinical trials in 2021, the field has experienced explosive growth, marked by a surge in patents for both inhibitors and degraders and the advancement of five candidates into clinical development. AREAS COVERED:This review covers an update of clinical trial reports and patent literature on PKMYT1 inhibitors from 2021 to December 2025, drawing on patent retrieved from the World Intellectual Property Organization (WIPO), the European Patent Office, and the Cortellis Drug Discovery Intelligence database. EXPERT OPINION:The rapid advancement of PKMYT1 inhibitors and degraders underscores their potential as a synthetic‑lethal therapeutic strategy for cancers with CCNE1 amplification or FBXW7 alterations. Clinical proof‑of‑concept for this approach has been established by RP‑6306 trial outcomes, while insights from this comprehensive review are expected to inform strategies addressing the current limitations in this field.
INTRODUCTION:Platelet-derived growth factor receptors (PDGFRs) play essential roles in cell growth, angiogenesis, and tissue repair, while their dysregulation is implicated in cancer and fibrotic disorders. PDGFR inhibitors have become important in precision medicine by enabling targeted therapy, slowing disease progression, and overcoming drug resistance which warrants search of new inhibitors. AREAS COVERED:A patent survey (2020-2025) focused on small-molecule PDGFR inhibitors has been carried out. Key aspects discussed include PDGFR inhibitory activity, antiproliferative effects, structural features critical for activity, and clinical relevance. EXPERT OPINION:The PDGFR inhibitors, as summarized in discussed patents, reveal that among the nitrogen containing heterocycles, the most active belonged to pyrazolopyrimidines, pyrazolothiazole carboxamides, and pyrrolo[1,2-b] pyridazines classes where hydrophobicity plays an important role in their activity. Although some of the compounds were specific to either the α or β receptor, many reported compounds lacked selectivity to other kinases as well. The smaller number of patents could also indicates a larger scope to address these issues and simultaneously identify novel PDGFR inhibitors.
INTRODUCTION:Activin receptor-like kinase 5 (ALK5) is a pivotal component of the transforming growth factor β (TGF-β) signaling pathway. Currently, 10 ALK5 inhibitors are under clinical investigation, with numerous others in preclinical stages, demonstrating broad therapeutic potential. However, no systematic review of ALK5 inhibitor-related patents has been conducted to date. Therefore, this study systematically reviews patents related to ALK5 inhibitors from 2013 to the present, providing a theoretical basis for discovering structurally novel, safe, and effective ALK5 inhibitors. AREAS COVERED:This paper briefly outlines ALK5 inhibitors currently in clinical development and ALK5-related patents published since 2013, retrieved through databases such as Google Patents, CAS SciFinder and PatSnap. EXPERT OPINION:ALK5 inhibitors have garnered significant interest in recent years for the treatment of TGF-β-related diseases, with encouraging outcomes observed in clinical trials. However, certain structural classes have been associated with adverse effects such as cardiotoxicity and bone toxicity. This review consolidates patent literature on ALK5 inhibitors, offering insights to support the development of novel, highly efficient, and low-toxicity inhibitors with improved pharmacokinetic profiles.
INTRODUCTION:A complicated process called angiogenesis creates new blood vessels from existing ones. Oxygen and nutrients from angiogenesis support tumor development, invasion, and metastasis. Many biological agents cause angiogenesis. EGF, FGF, VEGF, transcription factors, cytokines, adhesion molecules, proteinases, and growth factors. VEGF-A, B, C, and D are necessary for angiogenesis. VEGF family members interact with VEGFR-1,-2, and-3. Overexpression of VEGF proteins and receptors occurs during cancer progression. Novel signaling pathways, transcription factors, and mechanisms may help cure cancers by inhibiting angiogenesis. AREAS COVERED:This review discusses VEGFR-2 inhibitors patented since 2022 and their potential use in the management of angiogenesis-related disorders like cancer. EXPERT OPINION:Small-molecule VEGFR-2 inhibitors have minimal selectivity and cause fatigue, anorexia, hypertension, hemorrhage, and bleeding due to their affinity for PDGF, EGFR, and RAF, which is conserved in many tyrosine kinases. Poor pharmacokinetics, side effects, and high manufacturing costs may limit biomolecule adoption despite clinical success. Proangiogenic and non-tumor proangiogenic chemicals and myeloid cells produced treatment resistance. Thus, multimodal targeted medications or combination therapy with anti-angiogenic therapies, chemotherapeutic agents, immune checkpoint inhibitors, or gene therapy are needed to block pathological angiogenesis and increase selectivity, safety, diagnosis, and therapy response.
INTRODUCTION:With increasing knowledge and understanding of the molecular mechanisms of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and its role in inflammatory diseases, NLRP3 has emerged as a highly druggable target. This is reflected in extensive efforts to develop small molecule NLRP3 inhibitors with diverse chemical scaffolds and mechanisms of action (MOAs), aimed to achieve disease intervention. AREAS COVERED:The current review summarizes recent patents on NLRP3 inhibitor development from 2023 to present. In addition, the molecular mechanisms underlying NLRP3 activation and its involvement in inflammatory diseases were also discussed. The second objective is to get a comprehensive analysis of currently available patent applications and priority filings on NLRP3-targeted therapies with emphasis on new indications. EXPERT OPINION:This review provides an organized, systematic, and coherent overview of recent progress in NLRP3-targeted therapeutics and highlights the increasing diversity of chemical classes of new NLRP3 inhibitors, as well as the overall trend toward increased strategic activity across patent jurisdictions and territories.
INTRODUCTION:It is well established that isocoumarins and isoflavones exhibit intriguing biological effects. During the period 2018-2024 isocoumarins and isoflavones chemistry has attracted attention due to their biological and pharmaceutical properties. AREAS COVERED:This review focuses on patents relating to the therapeutic properties of isocoumarins and isoflavones between 2018 and 2024. The latest patented studies of isocoumarin and isoflavone are summarized by using the keywords 'isocoumarin' and 'isoflavone' in SciFinder, PubMed, and Google Patents databases in the year from 2018 to 2024. EXPERT OPINION:A wide range of important pharmaceutical properties are exhibited by isocoumarins and isoflavones and their synthetic analogs. In addition, isocoumarins and isoflavones have the potential to couple with other biologically active molecules, synergistically enhancing delivery and biological effects. In addition, scientists should direct their efforts toward the synthesis of halo-substituted and functionalized heterocyclic ring derivatives of isocoumarins and isoflavones, with a view to obtaining lead compounds. The lack of pharmacology and pharmacokinetics data along with in vivo studies for isocoumarins and isoflavones, prevents effective regulatory decisions from being proposed. In addition, detailed efficacy studies in well-established disease models are required to determine the clinical effects of isocoumarins and isoflavones.
INTRODUCTION:Monoamine oxidases (MAOs) A and B are key enzymes for the oxidative deamination of monoamine neurotransmitters, including dopamine, serotonin, norepinephrine, and tyramine. Selective MAO-B inhibitors are clinically employed as adjuvant therapies for neurodegenerative disorders, whereas selective MAO-A inhibitors are mainly considered third-line options in the treatment of depression. However, due to their function in regulating synaptic activity and exogenous monoamine metabolism, research in this field is continually expanding. AREAS COVERED:This review summarizes patents on MAO inhibitors between 2022 and 2025. For the most investigated chemotypes (14 synthetic cores along with compounds from natural sources), biological activities were analyzed. The compounds are divided into two main categories, naturally occurring molecules and newly synthesized derivatives, with a total of 114 compounds discussed. To provide a more comprehensive perspective on the therapeutic potential of these inhibitors, additional treatment alternatives are also outlined. EXPERT OPINION:Recently patented MAO inhibitors show notable properties, including significant isoform selectivity and therapeutic potential toward other diseases, such as fibromyalgia, CDKL5-deficient disorder, neuropathic pain, and Alzheimer's disease.
INTRODUCTION:Factor XII (FXII) is a liver-derived plasma zymogen that autoactivates on anionic surfaces to FXIIa, which drives the contact blood coagulation pathway, kallikrein-kinin signaling, fibrinolysis, and classical complement. Although congenital FXII(a) deficiency is largely asymptomatic, dysregulated activity is linked to thrombosis, hereditary angioedema (HAE), and neuroinflammation, making FXII(a) an attractive therapeutic target. AREAS COVERED:This review provides a brief overview of FXII/FXIIa structure and function to highlight its suitability as a therapeutic target. It then summarizes patents published between 2020 and 2025 (patent search using Espacenet, Google Patents, and SciFinder) covering FXII(a)-targeting agents across diverse modalities, including small molecules, proteins and peptides, monoclonal antibodies, oligonucleotides, and siRNAs. EXPERT OPINION:Patent analysis indicates that most FXII(a) inhibitors remain in early preclinical development, though a growing subset has shown in vivo efficacy in models of thrombosis, HAE, sepsis, and neuroinflammation. The breadth and pace of 2020-2025 filings, together with accumulating translational data, should accelerate progression from patents to clinical candidates, particularly for contact-activation indications (e.g. device-related thrombosis). Resolving full-length FXII/α-FXIIa structures would further enable allosteric inhibitors design.
INTRODUCTION:Inhibition of protein tyrosine phosphatase 1B (PTP1B) is a key strategy for improving insulin sensitivity in various cells. This strategy is supported by human genetic data. PTP1B inhibitors are considered an attractive target for the treatment of T2DM because they improve insulin receptor sensitivity and have the ability to reverse insulin resistance-related diseases. AREAS COVERED:This review provides an overview of the patents that were published between January 2019 and December 2023. The efficacy of potent PTP1B inhibitors for the treatment of T2DM is described in this review. The latest patented studies of PTP1B inhibitors (are summarized by using the keywords 'PTP1B inhibitors,' in PubMed, SciFinder, and Google Patents. EXPERT OPINION:There has been tremendous progress in PTP1B drug discovery. Progress has been made with natural products, semi-synthetic natural product derivatives and heterocyclic hybrid compounds. A number of protocols are being pursued in order to enhance the biological effects of PTP1B inhibitors. In addition, these new advances suggest that it may be possible to obtain small-molecule inhibitors of PTP1B with the required potency and selectivity. In addition, future efforts using an integrated medicinal chemistry and structural biology strategy are expected to lead to potent and selective PTP1B inhibitors.
