AZ 960 / AstraZeneca, Qiagen - LARVOL DELTA

Type 2 cytokine-JAK1 signaling is involved in the development of dry skin-induced mechanical alloknesis. (PubMed, J Dermatol Sci) - "Type 2 cytokine-JAK1 signaling is involved in the development of m-alloknesis in dry skin."

Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • IL13 • IL4 • JAK1 • TSLP

Thrombopoietin Receptor Signaling Promotes the Competitive Advantage of TET2-Mutated Hematopoietic Stem and Progenitor Cells in Clonal Hematopoiesis (ASH 2022) - "In line with our hypothesis, treatment with JAK2 inhibitors (fedratinib and AZ960), but not JAK1 inhibitors, suppressed the competitive advantage of Tet2KO HPCHOXB4 cells in vitro...In untreated cultures, the relative size of the mutant clones increased over time, an effect that was diminished by treatment with either SGC0946 or ruxolitinib...This differential dependency is mediated through increased H3K79 methylation at the MPL gene locus and enhanced expression of MPL. Furthermore, inhibition of the TPOR/JAK2 signaling axis is effective in suppressing the competitive advantage of TET2-mutated HSPCs, thus identifying a tractable therapeutic target for TET2-mutated CHIP."

Hematological Disorders • Hematological Malignancies • Oncology • DOT1L • HOXB4 • MPL • TET2

FAT10 stimulates the development of osteosarcoma by regulating the JAK/STAT signaling pathway. (PubMed, J BUON) - "FAT10 is upregulated in OS samples, which stimulates the development of OS by activating the JAK/STAT signaling pathway."

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • IFNG • STAT3 • STAT5 • TNFA

High MMP-11 expression associated with low CD8+ T cells decreases the survival rate in patients with breast cancer. (PubMed, PLoS One) - "We found that pictilisib and AZ960 effectively inhibited the breast cancer cell lines with high MMP-11 expression. Strategies making use of MMP-11-related hub genes could contribute to better clinical management/research for patients with breast cancer."

Clinical • Journal • Breast Cancer • Immunology • Oncology • Solid Tumor • Targeted Protein Degradation • CD4 • CD8

Design, synthesis, and characterization of 4-aminopyrazole quinazolines as potent inhibitors of G protein-coupled receptor kinase GRK6 for the potential treatment of multiple myeloma (AACR 2018) - "...Through this exercise, we discovered that two structurally distinct aminopyrazoles AZ-960 and ASC-082 had modest inhibition of GRK6. By combining structural features of these hits and further optimization we identified the quinazoline analogue OICR9945, a potent GRK6 inhibitor with good selectivity against a panel of diverse kinases and anti-proliferative activity against MM cell lines. Herein, we describe the design, synthesis and early pharmacological characterization of OICR9945 along with structure activity relationships (SAR) of this series against GRK6 and other kinases."

Leukemia • Multiple Myeloma

Phenotypic screen identifies JAK2 as a major regulator of FAT10 expression. (PubMed, ACS Chem Biol) - "We identified AZ960, a potent JAK2 inhibitor, which significantly downregulates FAT10 under pro-inflammatory cytokines induction, in an NFκB-independent manner. We validated JAK2 as a major regulator of FAT10 expression via knockdown, and suggest that the transcriptional effects are mediated through pSTAT1/3/5. Overall, we elucidated a pathway regulating FAT10 transcription and discovered a tool compound to chemically downregulate FAT10 expression, and further study its biology."

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