AZ191 / AstraZeneca - LARVOL DELTA

Discovery of the small molecular inhibitors against TRPV6 as potential anti-cancer agents by structural based virtual screening. (PubMed, Front Chem) - "In vitro experiments have demonstrated the efficacy of compound AZ191 in combating tumors by virtue of its inhibitory effect on TRPV6. Notably, our study further demonstrates the good potential of TRPV6 inhibitors as novel anti-cancer drugs and provides a good lead compound for TRPV6 inhibitor research."

Journal • Oncology • TRPV6

DYRK1B Inhibition by AZ191 Sensitizes High-Grade Serous Ovarian Cancer to Niraparib Through Promoting Apoptosis and Ferroptosis. (PubMed, Biomedicines) - "In addition, the combination therapy induces ferroptosis by inhibiting the Nrf2/SLC7A11/GPX4 axis, thereby exerting cytotoxic effects. Our results uncover a novel mechanism by which inhibiting DYRK1B enhances the anti-HGSOC efficacy of Niraparib and may offer a promising treatment strategy to improve the maintenance therapy in both HRD and HRP ovarian cancer patients."

Journal • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • DYRK1B • GPX4 • HRD • SLC7A11

Autophagy revealed as a targetable vulnerability in senescent cells by cell painting phenotypic profiling: a mechanistic study of MCOPPB and related compounds. (PubMed, Geroscience) - "Using Cell Painting-based morphological profiling, we identified a distinct cluster of senolytic compounds comprised of both known and novel autophagy inhibitors, including AZ191, bafilomycin A1, chloroquine, daurisoline, dauricine, MCOPPB, and its derivative MS1108. Our findings reveal senescent cell dependence on autophagy as an essential survival mechanism, define the existence of a mechanistically distinct class of senolytics acting through autophagy inhibition, and demonstrate the predictive value of Cell Painting in aging-related drug discovery. Our results provide new insights into senescent cell vulnerability and expand the therapeutic landscape for aging-related pathologies by highlighting autophagy as a targetable dependency."

Journal • Inflammation

Targeting hypoxic survival pathways to overcome radiotherapy-related treatment resistance (AACR 2024) - "The small molecule DYRK1B inhibitor AZ191 and shRNA-mediated DYRK1B knockdown significantly reduced proliferative activity and clonogenicity of SW620 tumor cells alone and in combination with IR under serum-starved conditions, which correlated with increased ROS levels and DNA damage...3'000 clinically relevant compounds in colorectal tumor cells lines under normoxic and hypoxic conditions in order to explore additional hypoxia-mediated survival pathways contributing to radioresistance. Thereby we aim to identify novel combined treatment modalities to overcome radiotherapy-induced hypoxia and hypoxia-related resistance mechanisms."

Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • DYRK1B

Core-shell hydrogel microspheres with sequential drug release and magnetothermal synergy for drug-resistant ovarian cancer. (PubMed, Biomater Sci) - "In vitro drug release experiments demonstrated that AZ191 exhibited rapid release within the first three hours with a cumulative release of approximately 26%, whereas cisplatin showed minimal early release (∼5%) followed by a markedly accelerated release. In vitro antitumor studies confirmed that the combined chemo-hyperthermia treatment using the core-shell MSs produced the most effective inhibitory effect on drug-resistant OC cells, reducing cell viability to 21% after 48 h, significantly outperforming either chemotherapy or hyperthermia alone. This strategy enables a "resistance-reversal first, precision-killing later" treatment model, offering a novel and effective solution for the treatment of drug-resistant OC."

Journal • Platinum resistant • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • DYRK1B

RNA-binding fluorogenic probes: G-clamp conjugated with a thiazole orange derivative for screening RNA-binding small molecules. (PubMed, RSC Chem Biol) - "FID assays using TO-G-clamp-Bn identified unique hit compounds that were insensitive to the well-known indicator TO-PRO-1. Furthermore, SHAPE-MaP analysis revealed the RNA-binding sites of TO-G-clamp, TO-PRO-1, and one of the hit compounds, AZ191, showing that the binding sites of TO-G-clamp were in close proximity to those of AZ191."

Journal

SUMOylation of DYRK1B facilitates gastric cancer metastasis by phosphorylating SFPQ (ESSO 2025) - "Furthermore, combined treatment with the DYRK1B inhibitor AZ191 and SUMOylation inhibitor TAK-981 significantly inhibited GC metastasis in mouse models.Conclusions (For surgical proposals, write down NA) CBX4/SENP1-regulated SUMOylation of DYRK1B enhances its kinase activity, which subsequently promotes GC invasion and metastasis by phosphorylating SFPQ and inducing its phase separation, thereby reprogramming global alternative splicing in GC cells. These findings provide novel molecular targets and highlight the clinical potential for therapeutic intervention in GC metastasis."

Gastric Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • DYRK1B

Structural perspective on the design of selective DYRK1B inhibitors. (PubMed, Int J Biol Macromol) - "We report the crystal structure of DYRK1B in complex with the small-molecule inhibitor AZ191...Moreover, detailed evaluation of the active site architecture reveals a notable difference in the accessibility of the catalytic lysine residue between DYRK1B and DYRK1A, suggesting potential strategies to distinguish selective binders. Overall, these findings provide important macromolecular insights into the DYRK1B structure and offer a structural framework to guide medicinal chemistry efforts towards improved inhibitor selectivity with minimized off-target activity."

Journal • Hepatology • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology • DYRK1B

DYRK1B phosphorylates FOXO1 to promote hepatic gluconeogenesis. (PubMed, Nucleic Acids Res) - "Further, AZ191, a pharmacological inhibitor of DYRK1B, significantly reduced blood glucose levels in diabetic mice. Collectively, these findings provide new insights into the role of DYRK1B in glucose metabolism and identify it as a new therapeutic target for treating diabetes."

Journal • Diabetes • Metabolic Disorders • DYRK1B

Identification of DYRK1b as a novel regulator of small extracellular vesicle release using a high throughput nanoscale flow cytometry screening platform. (PubMed, Nanoscale) - "The high-throughput flow cytometry screening platform quantified the effect of 156 kinase inhibitors on EV number and identified AZ191 - a DYRK1b inhibitor - as a potent EV inhibitor...DYRK1b knockdown altered the intracellular distribution of EV marker CD63, suggesting a role for DYRK1b in EV trafficking. In conclusion, our study establishes a platform for high-throughput analysis of EV dynamics and introduces DYRK1b kinase as a novel EV-regulator."

Journal • CD63 • DYRK1B

Hepatic Dyrk1b impairs systemic glucose homeostasis by modulating Wbp2 expression in a kinase activity-dependent manner. (PubMed, Heliyon) - "In addition, Dyrk1b inhibition with AZ191 moderately improved systemic glucose homeostasis. Our study uncovers that hepatic Dyrk1b impairs systemic glucose homeostasis via its modulation of Wbp2 expression in a kinase activity-dependent manner."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • DYRK1B • WBP2

Mirk/Dyrk1B Kinase Inhibitors in Targeted Cancer Therapy. (PubMed, Pharmaceutics) - "In this review, apart from summarizing the data establishing Dyrk1B as a therapeutic target in cancer, we highlight the most potent Mirk/Dyrk1B inhibitors recently reported. We also discuss the limitations and perspectives for the structure-based design of Mirk/Dyrk1B potent and highly selective inhibitors based on the accumulated structural data of Dyrk1A and the recent crystal structure of Dyrk1B with AZ191 inhibitor."

Journal • Review • Oncology • DYRK1B

Mirk/Dyrk1B controls ventral spinal cord development via Shh pathway. (PubMed, Cell Mol Life Sci) - "Especially, Dyrk1B overexpression decreases the numbers of ventral progenitors, MNs, and V2a interneurons, while the pharmacological inhibition of endogenous Dyrk1B kinase activity by AZ191 administration increases the numbers of ventral progenitors and MNs...Collectively, these observations reveal a novel regulatory function of Dyrk1B kinase in suppressing the Shh/Gli pathway and thus affecting ventral subtypes in the developing spinal cord. These data render Dyrk1B a possible therapeutic target for motor neuron diseases."

Journal • Amyotrophic Lateral Sclerosis • DYRK1B • GLI2 • GLI3 • SHH

Targeting the survival kinase DYRK1B: A novel approach to overcome radiotherapy-related treatment resistance. (PubMed, Radiother Oncol) - "Combined treatment with the DYRK1B inhibitor AZ191 and IR resulted in (supra-) additive tumor cell killing in colorectal tumor cell systems and in primary CRC organoids. Mechanistic investigations support the rational to target the stress-enhanced survival kinase DYRK1B in combination with irradiation to overcome hypoxia- and starvation-induced treatment resistances."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • DYRK1B

Analysis of DYRK1B, PPARG, and CEBPB Expression Patterns in Adipose-Derived Stem Cells from Patients Carrying DYRK1B R102C and Healthy Individuals During Adipogenesis. (PubMed, Metab Syndr Relat Disord) - "Furthermore, the new compound AZ191 exhibited inhibitory activity toward DYRK1B and CEBPB. We suggest that AZ191 may be helpful in defining the potential roles of DYRK1B and CEBPB in adipogenesis."

Journal • Cardiovascular • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus • CD34 • CD44 • ENG • PPARG • THY1