NSC348884 / Targeted Cancer Therap - LARVOL DELTA

CSN6 Promotes Pancreatic Cancer Progression and Gemcitabine Resistance via Antagonizing DCAF1-Mediated Ubiquitination of NPM1. (PubMed, Adv Sci (Weinh)) - "Significantly, combining gemcitabine with NPM1 inhibitor NSC348884 synergistically suppresses CSN6-high pancreatic cancer xenografts. This study characterizes CSN6 as an oncogenic protein that promotes NPM1 stabilization by interacting with DCAF1, thereby enhancing ribosome biogenesis and cellular resistance to gemcitabine in PDAC. NPM1 may serve as a therapeutic target for CSN6 high PDAC that exhibits gemcitabine drug resistance."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Targeted Protein Degradation • COPS6 • DDB1 • NPM1 • RRM1

NPM1 mediated up - regulation of CXCR4 might drive bortezomib resistance in multiple Myeloma. (PubMed, Hematology) - "Knockdown of NPM1 and treatment with the NPM1 inhibitor NSC348884 both restored the sensitivity of KB cells to BTZ. Further analysis revealed that inhibition of NPM1 down-regulated CXCR4 expression at both transcriptional and translational level. In conclusion, NPM1 might causes BTZ resistance via up-regulating CXCR4 expression in MM and could be served as both a new prognostic biomarker and a promising therapeutic target."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology • CXCR4 • NPM1

Identification of Immune-Related Ferroptosis Biomarkers in Diabetic Kidney Disease and Screening of Associated Inhibitors. (PubMed, Curr Med Sci) - "We identified ALOX5 as a reliable and prospective diagnostic marker associated with immunity and ferroptosis in DKD patients."

Biomarker • Journal • Diabetic Nephropathy • Inflammation • Nephrology • Renal Disease

Targeting NPM1 inhibits proliferation and promotes apoptosis of hepatic progenitor cells via suppression of mTOR signalling pathway. (PubMed, Stem Cell Res Ther) - "Targeting NPM1 inhibits proliferation and induces apoptosis in hepatic progenitor cells and BEL-7402 cells, thus serving as a potential therapy for cHCC-CCA."

Journal • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • IL6R • NPM1 • PCNA

Targeting NPM1 Epigenetically Promotes Postinfarction Cardiac Repair by Reprogramming Reparative Macrophage Metabolism. (PubMed, Circulation) - "Furthermore, NPM1 deficiency boosted the reparative function of cardiac macrophages by shifting macrophage metabolism from the inflammatory glycolytic system to oxygen-driven mitochondrial energy production., The oligomeric NPM1 mechanistically recruited histone demethylase KDM5b to the promoter of Tsc1 (TSC complex subunit 1), the mTOR (mechanistic target of rapamycin kinase) complex inhibitor, reduced histone H3K4me3 modification, and inhibited TSC1 expression, which then facilitated mTOR-related inflammatory glycolysis and antagonized the reparative function of cardiac macrophages. The in vivo administration of antisense oligonucleotide targeting NPM1 or oligomerization inhibitor NSC348884 substantially ameliorated tissue injury and enhanced cardiac recovery in mice after MI. Our findings uncover the key role of epigenetic factor NPM1 in impeding postinfarction cardiac repair by remodeling metabolism pattern and impairing the reparative function of cardiac..."

Journal • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology • Myocardial Infarction • KDM5B • NPM1 • TSC1

The effect of small molecule inhibitor NSC348884 on nucleophosmin 1-mutated acute myeloid leukemia cells. (PubMed, Eur Rev Med Pharmacol Sci) - "NSC348884 had inhibitory and proapoptotic effects on both wild-type and NPM1-mutated AML cells. The effect of NSC348884 on AML cells, carrying NPM1 mutation was significantly stronger."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • NPM1

Exploratory study on the potential regulating role of Peroxiredoxin 6 on proteolysis and relationships with desmin early postmortem. (PubMed, Meat Sci) - "The longissimus lumborum (LL) were obtained at 45 min postmortem from 6 beef carcasses and then incubated with or without the inhibitor of Prdx6 (NSC348884) for different times, followed by incubation with or without the HO (simulation of oxidative stress)...Moreover, the samples in which Prdx6 was inhibited demonstrated more severe desmin degradation accompanied by a higher apoptosis rate which was induced by the increase in caspase degradation as well as the ratio of Bax/Bcl-2. These results demonstrated that inhibiting Prdx6 could promote cell apoptosis and further accelerate beef tenderization."

IO biomarker • Journal • Targeted Protein Degradation • BAX • BCL2 • PRDX6

Discovery of Novel PI3Kδ Inhibitors Based on the p110δ Crystal Structure. (PubMed, Molecules) - "Idelalisib, which targets PI3Kδ specifically, is the first approved PI3K inhibitor for cancer therapy. Recently, we carried out virtual screening, cell-based assays, adapta kinase assays, and molecular dynamic analysis to discover novel PI3Kδ inhibitors and identified NSC348884 as a lead PI3Kδ inhibitor...In addition, we found that N, N, N-trimethyl-N-((6-methyl-1H-benzo[d]imidazol-2-yl) methyl) ethane-1,2-diamine might be a potential scaffold structure. Thus, the result of this study provides a far more efficient approach for discovering novel inhibitors targeting PI3Kδ."

Journal • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • PIK3CD

Current status and future perspectives in targeted therapy of NPM1-mutated AML. (PubMed, Leukemia) - "Starting from the structure and functions of NPM1, we provide an overview of the potential targeted therapies against NPM1-mutated AML and discuss strategies aimed at interfering with the oligomerization (compound NSC348884) and the abnormal traffic of NPM1 (avrainvillamide, XPO1 inhibitors) as well as at inducing selective NPM1-mutant protein degradation (ATRA/ATO, deguelin, (-)-epigallocatechin-3-gallate, imidazoquinoxaline derivatives) and at targeting the integrity of nucleolar structure (actinomycin D). We also discuss the current therapeutic results obtained in NPM1-mutated AML with the BCL-2 inhibitor venetoclax and the preliminary clinical results using menin inhibitors targeting HOX/MEIS1 expression. Finally, we review various immunotherapeutic approaches in NPM1-mutated AML, including immune check-point inhibitors, CAR and TCR T-cell-based therapies against neoantigens created by the NPM1 mutations."

IO biomarker • Journal • Review • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Targeted Protein Degradation • MEIS1 • NPM1

Cytoplasmic Role of Nucleophosmin (NPM1/B23) in Restricting Chikungunya Virus Replication in Human Astrocytic Cells (ASM Microbe 2022) - "Inhibition of this aggregation using a specific NPM1 oligomerization inhibitor, NSC348884, caused a significant dose-dependent enhancement in virus replication by plaque assay and CHIKV genomic/sub-genomic RT-PCR... Our studies demonstrated that the host protein NPM1/B23 exerts an antiviral role against CHIKV infection by interacting with specific viral proteins. A detailed delineation of these interactions will help focus on this protein as a cellular target in a host-directed paradigm of antiviral development against CHIKV."

Chikungunya • Infectious Disease • Musculoskeletal Pain • NPM1

NPM1 is a Novel Therapeutic Target and Prognostic Biomarker for Ewing Sarcoma. (PubMed, Front Genet) - "In addition, treatment with NPM1 promoted apoptosis and inhibited the proliferation of ES cells. The NPM1 inhibitor NSC348884 can induce apoptosis of ES cells in a dose-dependent manner and is expected to be a potential therapeutic agent for ES."

Biomarker • IO biomarker • Journal • Ewing Sarcoma • Oncology • Sarcoma • Solid Tumor • NPM1

Inhibition of nucleophosmin 1 suppresses colorectal cancer tumor growth of patient -derived xenografts via activation of p53 and inhibition of AKT. (PubMed, Cancer Biol Ther) - "In vitro, we show that NPM1 gene silencing enhanced the chemosensitivity of CRC cells and that pharmacological inhibition of NPM1 by NSC348884 triggered the onset of programmed cell death. Moreover, LY294002, an inhibitor of the PI3K/AKT pathway, restored the chemosensitivity of CRC cells expressing high levels of NPM1. The findings that NPM1's expression in CRC tissue correlates with prognosis and supports anti-apoptotic activity mediated by AKT signaling, further our understanding of the role of NPM1 in CRC."

Clinical • Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • NPM1

NSC348884 cytotoxicity is not mediated by inhibition of nucleophosmin oligomerization. (PubMed, Sci Rep) - "Instead, we document that NSC348884 cytotoxicity is rather associated with modified cell adhesion signaling. The cytotoxic mechanism of NSC348884 has therefore to be reconsidered."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • NPM1

Bmapaf-1 is Involved in the Response against BmNPV Infection by the Mitochondrial Apoptosis Pathway. (PubMed, Insects) - "Furthermore, the phenomenon of Bmapaf-1 in response to BmNPV infection was determined to be related to apoptosis using the apoptosis inducer NSC348884 and inhibitor Z-DEVD-FMK. Therefore, Bmapaf-1 is involved in the response against BmNPV infection by the mitochondrial apoptosis pathway. This result provides valuable data for clarifying the anti-BmNPV mechanism of silkworms and breeding of resistant silkworm strains."

Journal • Infectious Disease