NMI-900 / Nemucore - LARVOL DELTA

A multi-omics analysis of effector and resting treg cells in pan-cancer. (PubMed, Comput Biol Med) - "Last, we identified a few correlations between the expression of CCR8 and TNFRSF9 and sensitivity to several drugs, including COL-3, Chlorambucil and GSK1070916, in pan-cancer. Overall, these findings highlight new evidence that both Treg signatures are crucial regulators of cancer progression, providing potential clinical outcomes for cancer therapy."

IO biomarker • Journal • Pan tumor • Adrenal Cortex Carcinoma • Endometrial Cancer • Genito-urinary Cancer • Melanoma • Oncology • Solid Tumor • CCR8 • CTLA4 • FOXP3 • IL2RA • TNFRSF9

Identification of chemical inhibitors targeting long noncoding RNA through gene signature-based high throughput screening. (PubMed, Int J Biol Macromol) - "Then, screening of 8199 compounds by HTS2 assay identified that treatments of Hesperadin and GSK1070916 significantly mimic the expression pattern of the LINC00973 knockdown gene signature...Clinically, we further found that breast tumors with high expression of LINC00973 also show relatively high expression of AURKB or JUN, and vice versa. In summary, we established a novel high-throughput screening strategy to identify small molecules capable of targeting RNA, provided two promising compounds targeting LINC00973 and further shed light on the underlying transcriptional upregulation mechanism of LINC00973 within cancer cells."

Gene Signature • Journal • Breast Cancer • Oncology • Solid Tumor • AURKB • JUN

Aurora kinase B is required for growth and expansion of medulloblastoma cells in the tissue context. (PubMed, Neoplasia) - "We validated tumor suppressive activities of the AURKB inhibitor (AURKBi) Barasertib (AZD1152-HQPA) and the structurally unrelated compound GSK-1070916 in cerebellum slice culture models for SHH, and Grp3 MB...We revealed that the combination of AURKBi with the SRC/BCR-ABL inhibitor Dasatinib acts synergistically to repress tumor growth and expansion in the highly invasive MB cell model ONS-76, but not in Grp3 MB cells...In conclusion, we demonstrate that AURKB is essential for MB tumor growth and expansion in the tissue context and the inhibition of AURKB is equally efficient as irradiation in repressing tumor cell growth. In patients younger than three years, pharmacological targeting of AURKB may thus constitute a novel means to overcome radiotherapy limitations."

Journal • Brain Cancer • Medulloblastoma • Oncology • Solid Tumor • ABL1 • AURKB • BCR

Cell cycle inhibitors activate hypoxia-induced DDX41-STING pathway to mediate anti-tumor immune response in liver cancer. (PubMed, JCI Insight) - "We demonstrated that Paclitaxel (microtubule stabilizer), Palbociclib (cyclin dependent kinase 4/6 inhibitor), AZD1152 and GSK1070916 (aurora kinase B inhibitors) have anti-cancer functions beyond arresting cell cycle. We observed a trend that Paclitaxel suppressed STINGWT HCC more effectively than STINGKO HCC, suggesting that STING might contribute to the anti-tumor effects of Paclitaxel. Our study revealed the immune-mediated tumor-suppressing properties of cell cycle inhibitors and suggested combined treatment with immunotherapy as a potential therapeutic approach."

IO biomarker • Journal • Gastrointestinal Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • AURKB • DDX41 • HIF1A • STING

Identification and evaluation of candidate COVID-19 critical genes and medicinal drugs related to plasma cells. (PubMed, BMC Infect Dis) - "Additionally, we identified three potential small molecules (GSK-1070916, BRD-K89997465, and idarubicin) that target key hub genes in the network, suggesting a novel therapeutic approach. This study marks the first comprehensive exploration of plasma cells' role in COVID-19, offering new insights and potential therapeutic targets. It underscores the importance of a systematic approach to understanding and treating COVID-19, expanding the current body of knowledge and providing a foundation for future research."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • AURKB • KIF11 • TOP2A

Aurora B and Aurora C pools at two chromosomal regions collaboratively maintain chromosome alignment and prevent aneuploidy at the second meiotic division in mammalian oocytes. (PubMed, Front Cell Dev Biol) - "We found that kinetochore-microtubule attachments at single chromatids were corrected at both prometaphase II and metaphase II stages, but that single chromatids compared to paired chromatids were more prone to misalignments following treatment of oocytes with the Aurora B/C inhibitory drugs AZD1152 and GSK1070916. We conclude that the Aurora B/C pool at the inner central region stabilizes chromosome alignment during metaphase II arrest, while Aurora B/C localized at the kinetochore assist in re-establishing chromosome positioning at the metaphase plate if alignment is lost. Collaboratively these two pools prevent missegregation and aneuploidy at the second meiotic division in mammalian oocytes."

Journal

Cell cycle inhibitors exhibit anti-tumor immunomodulatory roles through the HIF-1-DDX41 cytosolic DNA sensing pathway in HCC (AACR 2024) - "Anti-mitotic agents including Paclitaxel (microtubule stabilizer), Palbociclib (CDK4/6 inhibitor) and AZD1152 and GSK1070916 (Aurora Kinase B inhibitors) can also eliminate cancer cells via an alternative mechanism - the activation of STING signaling. In summary, this study exhibited the novel immune-mediated aspect of cell cycle inhibitors in suppressing tumor growth. Our data suggested the potential combination regimen of cell cycle inhibitors and currently available immunotherapy with promising result."

Immunomodulating • IO biomarker • Hepatocellular Cancer • Oncology • AURKB • DDX41 • HIF1A

Machine learning-aided search for ligands of P2Y6 and other P2Y receptors. (PubMed, Purinergic Signal) - "The hit compound ABBV-744, an experimental anticancer drug with a 6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine scaffold, had multifaceted interactions with the P2YR family: hP2Y6R inhibition in a non-surmountable fashion, suggesting that noncompetitive antagonism, and hP2Y1R enhancement, but not hP2Y14R binding inhibition. Other machine learning-selected compounds were either weak (experimental anti-asthmatic drug AZD5423 with a phenyl-1H-indazole scaffold) or inactive in inhibiting the hP2Y6R. Experimental drugs TAK-593 and GSK1070916 (100 µM) inhibited P2Y14R fluorescent binding by 50% and 38%, respectively, and all other compounds by < 20%. Thus, machine learning has led the way toward revealing previously unknown modulators of several P2YR subtypes that have varied effects."

Journal • Machine learning • Asthma • Astrocytoma • Brain Cancer • CNS Disorders • Immunology • Metabolic Disorders • Oncology • Respiratory Diseases • Solid Tumor

Inverse Impact of Cancer Drugs on Circular and Linear RNAs in Breast Cancer Cell Lines. (PubMed, Noncoding RNA) - "However, they display opposite effects, circ/linVRK1 favors apoptosis whereas circ/linMAN1A2 stimulates cell migration, and only XL765 did not alter the ratio of other dangerous circ/linRNAs in MCF-7. In MDA-MB-231 cells, AMG511 and GSK1070916 decreased circGFRA1, as a good response to drugs. Furthermore, some circRNAs might be associated with specific mutated pathways, such as the PI3K/AKT in MCF-7 cells with circ/linHIPK3 correlating to cancer progression and drug-resistance, or NHEJ DNA repair pathway in TP-53 mutated MDA-MB-231 cells."

Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor

Clinical significance and immune landscape of cuproptosis-related lncRNAs in kidney renal clear cell carcinoma: a bioinformatical analysis. (PubMed, Ann Transl Med) - "Patients with low-risk scores were more sensitive to immunotherapy and the small molecular drugs GSK1904529A, tipifarnib, BX-912, FR-180204, and GSK1070916. Meanwhile, the high-risk group tended to be more sensitive to pyrimethamine, MS-275, and CGP-60474. Collectively, we constructed a cuproptosis-related lncRNA prognostic signature with a higher predictive accuracy compared to multiple clinicopathological parameters, which may provide vital guidance for therapeutic strategies in KIRC. Combination of more prognostic biomarkers may further improve the accuracy."

IO biomarker • Journal • Clear Cell Renal Cell Carcinoma • Oncology • Renal Cell Carcinoma • Solid Tumor

Aurora Kinase B/C Inhibitor GSK1070916 Specifically Targets Juvenile Myelomonocytic Leukemia Cells with SHP2(PTPN11) Mutation (ASH 2022) - "The colony-forming ability of primary JMML cells was completely inhibited under treatment of GSK1070916 (500 nM). In conclusion, aurora kinase B can be used as a promising therapeutic target for SHP2-mutant JMML patients, and the aurora kinase B/C inhibitor GSK1070916 could be a candidate for the treatment of JMML."

Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Chronic Myeloid Leukemia • Chronic Myelomonocytic Leukemia • Hematological Disorders • Hematological Malignancies • Juvenile Myelomonocytic Leukemia • Leukemia • Oncology • AURKA • AURKB • BCL2L1 • CASP3 • PTPN11

Bioinformatics and network-based screening and discovery of potential molecular targets and small molecular drugs for breast cancer. (PubMed, Front Pharmacol) - "Finally, we proposed 16 candidate repurposing drugs YM201636, masitinib, SB590885, GSK1070916, GSK2126458, ZSTK474, dasatinib, fedratinib, dabrafenib, methotrexate, trametinib, tubastatin A, BIX02189, CP466722, afatinib, and belinostat for BC through molecular docking analysis. Using BC cell lines, we validated that masitinib inhibits the mTOR signaling pathway and induces apoptotic cell death. Therefore, the proposed results might play an effective role in the treatment of BC patients."

Journal • Breast Cancer • Oncology • Solid Tumor • AURKA • BIRC5 • CDK1 • EGFR • KDM5B • MIR16 • MIR23b • MIR34A • SOX2 • TOP2A • TP63

KDELR3 Is a Prognostic Biomarker Related to the Immune Infiltration and Chemoresistance of Anticancer Drugs in Uveal Melanoma. (PubMed, Dis Markers) - "The IC50 of AP-24534, BHG712, bleomycin, camptothecin, cisplatin, cytarabine, GSK1070916, and tipifarnib was higher in the KDELR3 high-expression group. In conclusion, KDELR3 may be applied as a potential diagnostic and prognostic biomarker for UM patients."

Biomarker • IO biomarker • Journal • Eye Cancer • Immune Modulation • Immunology • Inflammation • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • CD4 • CD8

Genome-wide screening for the G-protein-coupled receptor (GPCR) pathway-related therapeutic gene RGS19 (regulator of G protein signaling 19) in bladder cancer. (PubMed, Bioengineered) - "We chose RGS19 as a therapeutic target gene in bladder cancer. The drug GSK1070916 was found to inhibit the effect of RGS19 via cell rescue experiments in vitro."

Biomarker • Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Purging human ovarian cortex of contaminating leukaemic cells by targeting the mitotic catastrophe signalling pathway. (PubMed, J Assist Reprod Genet) - "Purging of CML/AML metastases in ovarian cortex is possible by targeting the Mitotic Catastrophe Signalling Pathway using GSK1070916 without affecting the ovarian tissue. This provides a therapeutic strategy to prevent reintroduction of leukaemia and enhances safety of autotransplantation in leukaemia patients currently considered at high risk for ovarian involvement."

Journal • Acute Myelogenous Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • Ovarian Cancer • Transplantation • AURKB

Elevated ABCB1 Expression Confers Acquired Resistance to Aurora Kinase Inhibitor GSK-1070916 in Cancer Cells. (PubMed, Front Pharmacol) - "GSK-1070916 also showed high binding affinity to ABCB1 substrate-binding site in the computational docking analysis. In conclusion, our study provides strong evidence that ABCB1 can confer resistance to GSK-1070916, which should be taken into consideration in clinical setting."

Journal • Oncology • ABCB1

Overexpression of human ATP-binding cassette transporter ABCG2 contributes to reducing the cytotoxicity of GSK1070916 in cancer cells. (PubMed, Biomed Pharmacother) - "In summary, we revealed that overexpression of ABCG2 can cause GSK1070916 resistance in cancer cells. The combination of an ABCG2 inhibitor with GSK1070916 may be a rational strategy to overcome the drug resistance and should be considered for clinical investigation."

Journal • Oncology • ABCG2

Aurora B/C kinase inhibitor GSK1070916A in treating patients with advanced solid tumors (clinicaltrials.gov) - P1, N=38; Recruiting -> Completed.

Trial completion • Oncology