AZ191 / AstraZeneca - LARVOL DELTA

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

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

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