daporinad (APO866)
/ Valerio Therap
- LARVOL DELTA
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June 26, 2025
Integrated Workflow for Drug Repurposing in Glioblastoma: Computational Prediction and Preclinical Validation of Therapeutic Candidates.
(PubMed, Brain Sci)
- "Our findings using different cellular models suggest that this computational prediction model could constitute a valuable tool for drug repurposing in GBM and potentially in other tumors, which could accelerate the development of more effective cancer treatments."
Journal • Preclinical • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • NAMPT
June 17, 2025
Efficacy of NAMPT inhibition in T-cell acute lymphoblastic leukemia.
(PubMed, PLoS One)
- "We subsequently tested FK866 in vivo in PDX mouse models of T-ALL, and found that it significantly reduced the peripheral blood disease burden and prolonged the survival of leukemic mice (median survival of 60.5 vs 21 days, p = 0.0007). This screen for targetable pathways in T-ALL generated in vitro and in vivo preclinical data supporting NAMPT inhibition as a promising strategy for the treatment of T-ALL."
Journal • Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • KRAS • NAMPT
June 10, 2025
ROS-Responsive Hydrogel for Localized Delivery of Nampt and Stat3 Inhibitors Exhibits Synergistic Antitumor Effects in Colorectal Cancer Through Ferroptosis Induction and Immune Microenvironment Remodeling.
(PubMed, Adv Sci (Weinh))
- "Intriguingly, mass cytometry time-of-flight (CyTOF) analysis indicates that the combined treatment with FK866 and C188-9 exerts antitumor effects by increasing the infiltration of CD8+ T cells and neutrophils into the tumor, as well as enhancing the expression of immune-regulatory molecules, including IFN-γ, IL-10, and perforin. Thus, this localized treatment not only minimizes systemic adverse effects, but also markedly amplifies antitumor efficacy through the modulation of both tumor cells and the tumor immune microenvironment, representing a promising antitumor treatment strategy."
Journal • Colorectal Cancer • Oncology • Solid Tumor • CD8 • GPX4 • IFNG • IL10 • NAMPT
June 06, 2025
Visual Diagnostic Strategy for Assessing the Impact of Aerobic Glycolytic Processes on Tumor Growth and Therapy.
(PubMed, Nano Lett)
- "Moreover, the combined effect of FK866 with cisplatin can further inhibit tumor proliferation and progression. These findings indicate that the acidity of the tumor microenvironment can serve as a metric for evaluating the extent of aerobic glycolysis and its implications for tumor growth and treatment, offering a potentially valuable approach for assessing clinical drug efficacy."
Journal • Oncology • NAMPT
May 30, 2025
NAD+/Nrf2 signaling promotes osteogenesis by regulating oxidative level of BMSCs under mechanical stress.
(PubMed, Prog Orthod)
- "We identified that NAD+/Nrf2 signaling regulated oxidative level and thus promoted osteogenic commitment of BMSCs under cyclic stretch stress. Targeting NAD+ metabolism or administrating exogenous supplementation to promote bone rebuilding could be a prospective therapy to accelerate OTM."
Journal
May 11, 2025
Inhibition of NAMPT as a therapeutic strategy to suppress tumor growth in lymphangioleiomyomatosis.
(PubMed, Biochim Biophys Acta Mol Cell Res)
- "Current therapies, like rapamycin effectively stabilize disease progression but mainly exert cytostatic effects and promote autophagy, a survival mechanism in LAM cells. Additionally, using an in vivo chicken egg chorioallantoic membrane (CAM) model, we showed that FK866 treatment significantly reduces LAM tumor growth compared to controls suggesting that NAMPT inhibition disrupts metabolic and survival pathways critical for TSC2-deficient cell viability and tumor progression. Our results establish NAMPT as a promising therapeutic target for LAM, offering a two-prong strategy to suppress tumor growth and enhance apoptosis, providing an alternative to current mTOR-based therapies."
Journal • Metabolic Disorders • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • NAMPT • TSC1 • TSC2
May 07, 2025
Investigating the mechanisms by which low NAT1 expression in tumor cells contributes to chemo-resistance in colorectal cancer.
(PubMed, Clin Epigenetics)
- "Our study underscores the multifaceted role of NAT1 in modulating chemo-sensitivity, cellular metabolism, and angiogenesis in CRC. These findings position NAT1 as a compelling candidate for a biomarker and a potential therapeutic target, offering new avenues for CRC management."
IO biomarker • Journal • Colorectal Cancer • Oncology • Solid Tumor • NAT1
April 27, 2025
The Role of Visfatin in Gastric and Esophageal Cancer: From Biomarker to Therapeutic Target.
(PubMed, Cancers (Basel))
- "Therapeutic agents targeting visfatin, such as the inhibitor FK866, have shown promising results in reducing tumor proliferation by >50%, improving chemoresistance, and restoring antitumor immunity in preclinical studies...The standardization of measurement techniques and large-scale clinical studies is needed to validate its prognostic and predictive value. Future research should focus on optimizing visfatin-targeted therapies, particularly in the context of obesity-associated malignancies and chemoresistant tumors."
Biomarker • Journal • Review • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Genetic Disorders • Immune Modulation • Immunology • Obesity • Oncology • Solid Tumor • NAMPT
March 26, 2025
NAMPT inhibitor-resistant rhabdomyosarcoma models exhibit alterations in metabolic and genomic profiles [WITHDRAWN]
(AACR 2025)
- "Treatment with the clinical NAMPT inhibitor OT-82 results in complete tumor regressions in vivo, however, upon intermittent treatment, acquired resistance develops in some in vivo models...Resistance to multiple other NAMPT inhibitors (daporinad and KPT-9274) was observed in one of the resistant cell lines...Whole exome sequencing revealed that each resistant cell line has a distinct, previously unreported mutation in NAMPT. Together, these data suggest that acquired resistance to NAMPT inhibitors in RMS models involves cellular alterations in the biochemical, metabolomic, and genomic profiles of cells."
Oncology • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • NAMPT • QPRT
April 16, 2025
Small Extracellular Vesicle-Derived Nicotinamide Phosphoribosyltransferase (NAMPT) Induces Acyl-Coenzyme A Synthetase SLC27A4-Mediated Glycolysis to Promote Hepatocellular Carcinoma.
(PubMed, J Extracell Vesicles)
- "This study uncovers a novel regulatory axis involving sEV-NAMPT and SLC27A4 in glycolysis, independent of traditional fatty acid metabolism pathways. Clinically, targeting sEV-NAMPT with the inhibitor FK866 significantly inhibited tumour growth in various HCC in vivo models, highlighting the potential of sEV-NAMPT as both a biomarker and therapeutic target in HCC."
IO biomarker • Journal • Hepatocellular Cancer • Metabolic Disorders • Oncology • Solid Tumor • NAMPT • TLR4
March 21, 2025
Suppression of ATP-dependent (S)-NAD(P)H-hydrate dehydratase expression inhibits adipocyte differentiation of 3T3-L1 preadipocytes by increasing excessive accumulation of NADHX.
(PubMed, J Biochem)
- "FK866, a specific inhibitor of NAMPT, further reduced lipid accumulation even in Naxd-silenced cells with substantial decrease in NAD+...In contrast, exposure of wild-type 3T3-L1 cells to NADHX recapitulated the Naxd deficiency-elicited inhibitory effects on adipocyte differentiation with reduced expression of master transcriptional regulators of adipogenesis, peroxisome proliferator-activated receptor γ and CCAAT/enhancer binding protein α. These results suggest that NAXD supports normal adipogenesis, in part, by inhibiting excessive accumulation of NADHX."
Journal • NAMPT
February 14, 2025
Metabolomic insights into pathogenesis and therapeutic potential in adult acute lymphoblastic leukemia.
(PubMed, Proc Natl Acad Sci U S A)
- "The combined use of simvastatin with vincristine and dexamethasone regimen demonstrated a synergistic therapeutic effect in a murine ALL model, effectively lowering key BA levels in serum and suppressing the infiltration of leukemic blasts in the liver. In light of the enhanced intracellular redox metabolism, combining FK866 (a nicotinamide phosphoribosyltransferase inhibitor) and venetoclax significantly prolonged survival in a patient-derived xenograft ALL model. Our findings, along with the resulting resources (http://www.genetictargets.com/MALL), provide a framework for the metabolism-centered management of ALL."
Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • NAMPT
February 13, 2025
Dual Roles of Canagliflozin on Cholangiocarcinoma Cell Growth and Enhanced Growth Suppression in Combination with FK866.
(PubMed, Int J Mol Sci)
- "Canagliflozin inhibits cholangiocarcinoma cell growth and migration and its anti-tumor effect is enhanced when combined with an NAMPT inhibitor. However, further investigation is required because of its potential tumor growth-promoting effect through the activation of the NAD+ salvage pathway."
Journal • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • NAMPT
February 03, 2025
Period3 modulates the NAD+-SIRT3 axis to alleviate depression-like behaviour by enhancing NAMPT activity in mice.
(PubMed, J Adv Res)
- "These findings uncover a novel mechanism by which PER3 ameliorates depressive behaviors through the regulation of NAMPT-controlled NAD+ levels and mitochondrial function, underscoring the critical role of PER3 in depression-related pathophysiology."
Journal • Preclinical • CNS Disorders • Depression • Metabolic Disorders • Mood Disorders • Psychiatry • ARNTL • BMAL1 • NAMPT • PER3 • SIRT3
January 28, 2025
Decrease of NAD+ Inhibits the Apoptosis of OLP T Cells via Inducing Mitochondrial Fission.
(PubMed, J Inflamm Res)
- "OLP T cells and OLP plasma-exposed Jurkat T cells were treated with either β-nicotinamide mononucleotide (an NAD+ synthesis precursor) or FK866 (an NAD+ synthesis inhibitor) to assess the effect of NAD+ regulation on mitochondrial remodeling and T cell apoptosis...Reduced NAD+ levels in OLP T cells enhanced mitochondrial fission and contributed to decreased apoptosis. NAD+ supplementation mitigated these effects, suggesting a potential therapeutic strategy for restoring T cell homeostasis in OLP."
Journal • Dermatology • Dermatopathology • Inflammation • Lichen Planus • MFN2
November 06, 2024
Identification of Nuclear NAD+ Salvage As a Therapeutic Vulnerability in B-Lymphoid Malignancies
(ASH 2024)
- P1 | "Approaches for targeted elimination of B-cells as the root-cause of disease have been highly effective in the treatment of B-ALL (e.g. CD19 CAR-T cells) and mature B-cell lymphoma (rituximab, ibrutinib), yet therapy resistance necessitates the identification of additional B-cell selective therapeutics...Chemogenomic CRISPR screening in FK866-treated NALM6 cells revealed that loss of nuclear NAD+ and ATP utilizing enzymes involved in epigenetic regulation, protein deacetylation and DNA damage response, rescues the effect of NAMPT inhibition...We validate the NMNAT1-NAMPT nuclear NAD-salvage axis as a therapeutic vulnerability in B-ALL and identify the likely underlying mechanism. Future research will extend pre-clinical testing of the three FDA-approved NAMPT inhibitors for repurposing to target therapy resistant B-ALL."
IO biomarker • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Metabolic Disorders • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • ABL1 • BCR • CEBPA • NAMPT • NNMT
November 06, 2024
Comprehensive Drug Profiling and CRISPR Screening Reveal Essential Pathways for NK Cell Cytotoxicity
(ASH 2024)
- "In addition, pevonedistat, daporinad, and bryostatin 1 enhanced NK cell activity, whereas sotrastaurin showed strong NK cell-inhibiting effects...Various NAMPT inhibitors (KPT-9274, GMX1778 and LSN3154567) not included in the original screens showed similar effects to daporinad in AML and ALL cell lines...In conclusion, our study identifies PKC, NAMPT, and NEDD8 having an essential role in controlling NK cell-mediated killing and suggests potential compounds to enhance NK cell effectiveness in treating hematological malignancies. These findings offer insights into developing combination immunotherapy strategies to improve treatment outcomes."
Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Chronic Myeloid Leukemia • Diffuse Large B Cell Lymphoma • Gene Therapies • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Targeted Protein Degradation • CXCR4 • IFNG • IL2RA • LGALS3 • NAMPT • NQO1
November 18, 2024
Identification of a Novel 4-gene Prognostic Model Related to Neutrophil Extracellular Traps for Colorectal Cancer.
(PubMed, Turk J Gastroenterol)
- "Additionally, 18 drugs displayed differential sensitivity between NETs_high and NETs_low groups, with Daporinad and Selumetinib as potential therapeutic options. Our findings may catalyze the development of personalized treatment modalities and bestow invaluable insights into the intricate dynamics governing CRC progression."
Biomarker • Journal • Colorectal Cancer • Oncology • Solid Tumor
November 01, 2024
Understanding the development of enzalutamide resistance based on a functional single-cell approach.
(PubMed, bioRxiv)
- "Single-cell RNA-Sequencing reveals heterogeneities of tumor cell populations. In most cases, however, the functional significance of the observed heterogeneity is not tested. In this study, we first identified a possible therapy-resistant prostate cancer cell subpopulation with scRNA-Seq, then confirmed the resistant phenotype with single cell and colony - based cloning and functional testing. In addition, we also identified a therapeutic vulnerability of the resistant cells."
Journal • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor
November 04, 2024
Nampt/SIRT2/LDHA pathway-mediated lactate production regulates follicular dysplasia in polycystic ovary syndrome.
(PubMed, Free Radic Biol Med)
- "Therefore, the PCOS rat model was established by combining letrozole with a high-fat diet (HFD), we demonstrate that in vivo supplementation of nicotinamide mononucleotide (NMN) significantly improves the ovulatory dysfunction by facilitating the follicular development, promoting luteal formation, as well the fertility in PCOS rats...We confirmed that FK866 can enhance the acetylation of LDHA on 293T cells by Co-immunoprecipitation (Co-IP) assay...Overall, these benefits of NMN were elucidated and the Nampt/SIRT2/LDHA pathway mediated lactate production in granulosa cells played an important role in the improvement of follicular development disorders in PCOS. This study will provide experimental evidence for the clinical application of NMN in the treatment of PCOS in the future."
Journal • Developmental Disorders • Metabolic Disorders • Polycystic Ovary Syndrome • LDHA • NAMPT • SIRT2
September 27, 2024
Targeting iNAMPT to Break the Obesity-associated Liver Cancer Link: An In Vivo Approach
(OBESITY WEEK 2024)
- "At 23 weeks, mice received an I.P. injection of FK866 (iNAMPT inhibitor) for 2 weeks... Identifying pre-clinical strategies to reverse the impact of obesity on liver cancer progression is important due to the strongly increased risk of liver cancer and its poor prognosis. Targeting energy production by inhibiting a key enzyme in NAD biosynthesis, iNAMPT, may be a novel strategy to break the obesity-cancer link."
Preclinical • Gastrointestinal Cancer • Genetic Disorders • Hepatology • Liver Cancer • Obesity • Oncology • Solid Tumor • BCL2L1 • NAMPT • PARP1
November 03, 2024
Regulatory roles of NAMPT and NAD+ metabolism in uterine leiomyoma progression: Implications for ECM accumulation, stemness, and microenvironment.
(PubMed, Redox Biol)
- "Targeting NAMPT, particularly through the use of inhibitors FK866 and NAM, represents a promising therapeutic approach for mitigating UL progression by modulating redox and ECM dynamics. These findings offer novel insights into UL pathogenesis and establish NAMPT as a compelling target for future clinical investigation."
Journal • Oncology • Solid Tumor • Uterine Leiomyoma • NAMPT
September 30, 2024
Intra-testicular visfatin inhibition disrupts androgen and estrogen signalling in the mouse testis.
(PubMed, Reprod Biol)
- "Visfatin has a stimulatory role in testosterone synthesis and proliferation in the testis. Moreover, some deregulated factors in the testis after 1 week of FK866 treatment, despite normal histoarchitecture treatment, could be a compensatory mechanism after visfatin inhibitions."
IO biomarker • Journal • Preclinical • BCL2 • CASP3 • NAMPT
September 29, 2024
The Fluorinated NAD Precursors Enhance FK866 Cytotoxicity by Activating SARM1 in Glioblastoma Cells.
(PubMed, Biology (Basel))
- "The synthesized analogue of nicotinamide riboside (NR), ara-F nicotinamide riboside (F-NR), inhibits nicotinamide ribose kinase (NRK) activity in vitro, reduces cellular NAD levels, and enhances FK866's cytotoxicity in U251 glioblastoma cells, indicating a collaborative impact on cell death. Temporal analysis underscores the sequential nature of events, establishing NAD depletion as a precursor to ATP depletion and eventual massive cell death. This study not only elucidates the molecular intricacies of glioblastoma cell death but also proposes a promising strategy to enhance FK866 efficacy through fluorinated NAD precursors, offering potential avenues for innovative therapeutic interventions in the challenging landscape of glioblastoma treatment."
Journal • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • NAMPT
June 01, 2024
The therapeutic potential of NAMPT in protecting against chronic thromboembolic pulmonary hypertension
(ERS 2024)
- "In addition, NAMPT inhibitor FK866,isstudy the regulatory effect of NAMPT on smooth muscle proliferation...On the contrary, increasing the expression of NAMPT can effectively inhibit smooth muscle proliferation(Figure E,N=3,P<0.05). Conclusion In summary, reduced NAMPT expression in CTEPH patients,coupled with elevated expression of aging-related genes, may be associated wth pathogenesis of CTEPH."
Cardiovascular • Pulmonary Arterial Hypertension • Pulmonary Disease • Pulmonary Embolism • Respiratory Diseases • CDKN1A • NAMPT
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