daporinad (APO866) / Valerio Therap - LARVOL DELTA

Combination of NAMPT inhibitors plus pyrimidine analog antimetabolites floxuridine and 5-FU impair rhabdomyosarcoma proliferation and survival (AACR 2026) - "Previously, we showed that RMS is highly sensitive to NAMPT inhibition, with in vivo RMS models undergoing tumor regression upon treatment with the NAMPT inhibitor OT-82...To identify synergistic drug combinations, we used a matrix drug screen of 2 RMS cell lines (Rh30 (fusion-positive (FP)) and Rh36 (fusion-negative (FN)) testing 2 NAMPT inhibitors (daporinad and GNE-618) in combination with 62 other anticancer agents...To evaluate this combination for potential translation into the clinic, we extended our testing to include clinical agents, including RPT1G (Remedy Plan Therapeutics), a NAMPT inhibitor currently under early phase evaluation, and 5-FU, a prodrug of floxuridine...Efficacy experiments are ongoing and will be reported. These findings demonstrate that combining NAMPT inhibitors with floxuridine or 5-FU results in significant synergy and preliminarily suggest that this is a promising and feasible combination regimen for patients with RMS."

Oncology • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • NAMPT • TYMS

The NAMPT Inhibitor FK866 Attenuates DEN-Induced Liver Fibrosis in Mice. (PubMed, Biol Pharm Bull) - "Further studies revealed that this therapeutic effect was achieved by inhibiting the NAD+ level, as well as the protein expression of NAMPT, PARP1, and inflammatory factors, including interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α, and P65. In conclusion, FK866 exhibits therapeutic potential for the treatment of liver fibrosis."

Journal • Preclinical • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Oncology • FN1 • IL1B • IL6 • NAMPT • TNFA

Nicotinamide N-Methyl Transferase (NNMT) Sustains Innate Sensitivity to NAMPT Inhibition in YAP-dependent Stem-like/Mesenchymal Prostate Cancer. (PubMed, Int J Biol Sci) - "Resistance to NAMPT inhibitors, such as FK866, remains a key limitation to their clinical translation...These findings support the use of NNMT as a predictive biomarker for NAD+-targeting therapies and provide mechanistic insight into a metabolic vulnerability of the CRPC-SCL subtype. Targeting the YAP/NNMT/NAMPT axis may represent a novel strategy for treating stem-like/mesenchymal, therapy-resistant prostate cancers."

Journal • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • NAMPT • NNMT

Targeting Metabolic and pH Regulatory Pathways in Cancer via Dual Inhibition of Nicotinamide Phosphoribosyltransferase and Carbonic Anhydrases IX and XII. (PubMed, J Med Chem) - "In three-dimensional (3D) spheroids, compound 45 reduced the cumulative spheroid area approximately 10-fold more than the single-target inhibitors FK866 or SLC-0111 and induced apoptosis through NAD depletion, mitochondrial dysfunction, and suppression of ERK/mTOR signaling. These results support dual hCA IX/XII-NAMPT inhibition as an effective strategy to impair tumor growth and survival under hypoxic stress."

Journal • Brain Cancer • Colorectal Cancer • Glioblastoma • Kidney Cancer • Metabolic Disorders • Oncology • Renal Cell Carcinoma • Solid Tumor • NAMPT

Single-Cell RNA sequencing identifies NAMPT as a potential therapeutic target in autoimmune uveitis. (PubMed, J Adv Res) - "Inhibiting NAMPT can reverse the imbalance of effector T (Teff)/Treg cells by suppressing the expression of Hif1α in CD4+T cells, thereby effectively alleviating the symptoms of EAU. Therefore, NAMPT might be a potential target for AU."

Journal • Immunology • Ocular Inflammation • Ophthalmology • Uveitis • CD4 • HIF1A • NAMPT

Exploring the role of CCT7 in prognosis, cell cycle regulation, and immune microenvironment remodeling of lung adenocarcinoma based on multi-omics datasets and functional experiments. (PubMed, Biochim Biophys Acta Gen Subj) - "CCT7 acts as an independent prognostic biomarker in LUAD, driving progression through cell cycle regulation, microenvironment remodeling, and immune modulation. It holds promise as a therapeutic target and guide for personalized LUAD treatment."

Journal • Tumor mutational burden • Immune Modulation • Immunology • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8 • FOXM1 • MIR145 • TMB

RAS/PI3K pathway mutations sensitise epithelial ovarian cancer cells to a PARP/NAMPT inhibitor combination. (PubMed, Commun Biol) - "Combined exposure to olaparib and FK866 is associated with a reduction in nicotinamide mononucleotide (NMN) and the PARP substrate nicotinamide adenine dinucleotide (NAD+), with coincident increases in ROS production, DNA damage and apoptosis induction. Finally, the combination significantly reduces omental tumour weight and increases overall survival in mice injected with ID8 Trp53-/-;Pten-/- cells. This study highlights the potential of the PARPi/NAMPTi combination in RAS/PI3K pathway mutant EOC."

Journal • Breast Cancer • Epithelial Ovarian Cancer • Ewing Sarcoma • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor • Triple Negative Breast Cancer • CASP3 • CASP7 • NAMPT • PTEN • TP53

Common Biomarkers and Pathogenesis of Inflammatory Bowel Disease and Breast Cancer: Mendelian Randomization and Multi-Omics Studies. (PubMed, Breast Cancer (Dove Med Press)) - "THBS3-high breast cancer patients exhibited resistance to Dinaciclib, Daporinad, and Rapamycin. THBS3 may promote breast cancer progression through immune regulation, ECM remodeling, and drug resistance mechanisms, suggesting its potential as a therapeutic target. These findings support enhanced breast cancer screening in IBD patients."

Biomarker • Journal • Breast Cancer • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Oncology • Solid Tumor • Ulcerative Colitis • MIR423

NAMPT in macrophages promotes multiple myeloma drug resistance through mitochondrial metabolic reprogramming and modulates immunosuppression via the SIRT1/STAT3/SPP1 axis. (ASH 2025) - "We found that NAMPT knockdown and FK866 inhibition contributed to a pro-inflammatoryphenotype shift in MΦs, with the upregulation of CD80, CD86, IL1b, IL6 and downregulation of CD163,CD206(MRC1). Co-culture experiments demonstrated that mMΦs protected H929 and JJN3 cells frombortezomib-induced apoptosis at high concentrations. Intratumoral injection of NAMPT-silenced mMΦssignificantly impaired tumor progression and resensitized NSG mice xenograft models to bortezomibtreatment."

IO biomarker • Hematological Malignancies • Metabolic Disorders • Multiple Myeloma • CD163 • CD8 • CD80 • CD86 • CSF1 • GZMB • HAVCR2 • IFNG • IL1B • IL6 • ITGA4 • LAG3 • MRC1 • NAMPT • SPP1 • STAT3

Anticancer sensitivities and biological characteristics of HCT116 cells resistant to the selective poly(ADP-ribose) glycohydrolase inhibitor. (PubMed, FEBS Open Bio) - "Interestingly, HCT116RPDD cells exhibited greater sensitivity to γ-ray irradiation and the nicotinamide phosphoribosyltransferase (NAMPT) inhibitor FK866 than the parental HCT116 cells, yet showed comparable sensitivity to 5-FU, cisplatin, and PARP inhibitors olaparib, talazoparib, and veliparib. Furthermore, we observed that HCT116RPDD cells tended to maintain slightly higher levels of intracellular NAD+/NADH and ATP compared to parental HCT116 cells. These findings suggest that cancer cells employ a mechanism to regulate NAD+ and ATP levels, thereby avoiding cell death from intracellular PAR accumulation through coordinated PARP-PARG regulation."

Journal • Colorectal Cancer • Oncology • Solid Tumor • NAMPT

Computational Discovery and Validation of NAD+ Biosynthesis As Unique Vulnerability in B-Lymphoid Malignancies (ASH 2023) - P1 | "Likewise, inhibitors of B-cell signaling (e.g. ibrutinib) and selective depletion of B-cells (e.g. rituximab, CD19 CAR-T cells) have achieved important progress and are well tolerated...To verify these results based on the DepMap dataset and our drug discovery tool (lymphoblasts.org), we studied the effects of seven NAMPT inhibitors (CAY10618, FK866, GMX1778, OT82, STF118804, STF31 and KPT9274) on a panel of myeloid leukemia and solid tumor cell lines as well as PDX from patients with B-ALL and mantle cell lymphoma... These findings highlight that the classical 'glucocorticoid paradigm' can be extended to discover novel vulnerabilities, including NAD+ biosynthesis. Computational integration of genetic and pharmacological compound screens was particularly powerful in identifying previously unrecognized opportunities to leverage selective vulnerabilities of B-lymphoid leukemia and lymphoma. Our genetic studies corroborate the unique role of NAMPT and NMNAT1 in..."

Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Metabolic Disorders • Oncology • Solid Tumor • ABL1 • BCR • NAMPT

Targeting NQO1 and the NAD+ Salvage Pathway: A Novel Therapeutic Strategy for Glioblastoma (SNO 2025) - "We demonstrate that targeting the NAD+ salvage pathway with the nicotinamide phosphoribosyltransferase (NAMPT ) inhibitor FK866 prevents NAD+ regeneration after β-lap exposure and enhances β-lap cytotoxicity in NQO1-expressing GBM. These findings suggest that identifying and targeting NQO1-expressing GBM with NQO1 bioactivatable compounds in conjunction with NAMPT-inhibitors is a promising therapeutic strategy for the treatment of GBM."

Brain Cancer • Glioblastoma • Solid Tumor • NAMPT • NQO1

Decoding colorectal cancer chemotherapy and immunotherapy resistance: revealing the role of NOL3 using single-cell RNA sequencing and machine learning. (PubMed, Clin Exp Med) - "Drug sensitivity analysis confirmed its involvement in chemotherapy resistance, and the impact of NOL3 on the efficacy of Daporinad was evaluated using MTT assays...CellChat analysis suggested that High_NOL3_Epithelial may interact with various immune cells through signaling pathways such as EGF, SAA, and TWEAK, contributing to immune therapy resistance. We established a composite prognostic model by combining features from hypoxia and PCD gene sets and validated NOL3 as a dual biomarker, offering significant clinical implications for prognostication and the tailoring of immunotherapy and chemotherapy in CRC patients."

Biomarker • IO biomarker • Journal • Colorectal Cancer • Oncology • Solid Tumor • EGF • TNFSF12

Deficiency of SARM1 attenuates neuronal injury and improves neurological performance in a photothrombotic stroke model. (PubMed, Mol Brain) - "FK866 and DSRM-3716, two recently reported pharmacological inhibitors of SARM1, failed to alleviate brain injury in mice with stroke. Our findings demonstrate that SARM1 deficiency attenuates ischemic neuronal injury and improves neurological performance post PTI, suggesting that the SARM1 signaling pathway could serve as a potential therapeutic target for stroke in the future."

Journal • Cardiovascular • CNS Disorders • Inflammation • Ischemic stroke • Vascular Neurology • TNFA

Targeting NQO1 and the NAD+ Salvage Pathway: A Novel Therapeutic Strategy for Glioblastoma (WFNOS 2025) - "We demonstrate that targeting the NAD+ salvage pathway with the nicotinamide phosphoribosyltransferase (NAMPT ) inhibitor FK866 prevents NAD+ regeneration after β-lap exposure and enhances β-lap cytotoxicity in NQO1-expressing GBM. These findings suggest that identifying and targeting NQO1-expressing GBM with NQO1 bioactivatable compounds in conjunction with NAMPT-inhibitors is a promising therapeutic strategy for the treatment of GBM."

Brain Cancer • CNS Tumor • Glioblastoma • Oncology • NAMPT • NQO1

A Novel Transgenic Mouse Model of Down Syndrome Acute Lymphoblastic Leukemia Identifies Targetable Vulnerabilities (ASH 2023) - "We screened top candidate drugs in DS-ALL and non-DS ALL patient samples in vitro, and tested FK866 and cucurbitacin I in vivo in mice xenografted with a DS-ALL patient sample. We have generated the first de novo mouse model and cell lines recapitulating DS-ALL, which we have employed in drug screens to identify novel therapeutic approaches. These studies suggest promising candidates for further study in DS-ALL and other high-risk ALL subtypes to reduce toxicity and improve outcomes."

Preclinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Developmental Disorders • Genetic Disorders • Hematological Malignancies • Leukemia • Oncology • KRAS • NAMPT • PAX5

Role of Nicotinamide Phophoribosyltransferase (NAMPT) in Regulating Nicotinamide Adenine Dinucleotide (NAD+) Metabolism and Tubular Injury Response During AKI (KIDNEY WEEK 2025) - "As expected, pharmacological inhibition of NAMPT with FK866 resulted in intracellular NAD+ depletion and significantly increased the expression of kidney injury markers. Conclusion These findings indicate that NAMPT is essential for maintaining NAD+ homeostasis in proximal tubule cells, and its loss leads to increased susceptibility to injury. This underscores the critical role of NAD+ metabolism in protecting against acute kidney injury and highlights NAMPT as a potential therapeutic target."

Acute Kidney Injury • Inflammation • Nephrology • Renal Disease • NAMPT • TNFA

Targeting NAD+ Salvage Suppresses PBMC Inflammation to Improve Cognitive Function in Vascular Cognitive Impairment. (PubMed, Stroke) - "Pharmacological inhibition of eNAMPT with FK866 reduced inflammation in VCI PBMCs...Our findings suggest peripheral inflammation driven by impaired NAD+ salvage and elevated eNAMPT levels in PBMCs plays a key role in VCI pathogenesis. Restoring NAD+ homeostasis via 5'-phosphoribosyl-pyrophosphate treatment significantly improved cognition in VCI mice, highlighting NAD+ salvage as a potential therapeutic target."

Journal • Alzheimer's Disease • Cognitive Disorders • Inflammation • NAMPT • TLR4

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

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 Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Targeted Protein Degradation • CXCR4 • IFNG • IL2RA • LGALS3 • NAMPT • NQO1

Molecular characterization of macrophage-related prognostic factors in glioblastoma revealed by combined analysis on single-cell and bulk transcriptome data. (PubMed, Discov Oncol) - "This study reveals the molecular characteristics of key prognostic factors in GBM, highlighting the importance of immune cell abundance and drug sensitivity in glioma treatment, and provides potential biomarkers and therapeutic targets for future clinical research and treatment strategies."

Biomarker • IO biomarker • Journal • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • CTLA4 • G0S2 • PD-1 • PD-L1 • TGM2 • TIGIT

Chemoproteomic-enabled fragment-based drug discovery target identification in small cell lung cancer (AACR-NCI-EORTC 2025) - "Pulldown, followed by Western Blot assays, confirmed the interaction between NAMPT and probe 30 (P30), which was competed for pretreatment with NAMPT inhibitors (NAMPTi), FK866, and GNE617...Together, our findings highlight NAMPT as an essential target in SCLC and identify P30 as a novel NAMPT inhibitor that may exert its effects through additional mechanisms. These results provide a foundation for future target validation and medicinal chemistry efforts to expand therapeutic options in SCLC."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • NAMPT

Metabolic Changes in Living Human Lymphoma Cells Intervening NAD+ Metabolism as Revealed by NAD(P)H-Fluorescence Lifetime Imaging and Para-Hydrogen-Induced Polarization NMR. (PubMed, Cytometry A) - "For proof of principle, NAD+-metabolism was perturbed by specific inhibition of the rate-limiting enzyme of the NAD+ "Salvage pathway" Nicotinamide phosphoribosyltransferase (NAMPT) by FK866 in RAMOS human lymphoma cells...This strongly supports NAD(P)H-FLIM analysis and demonstrates that intervening in the NAD+ "Salvage pathway" can have specific and global consequences for cells. Our principle study shows how spatially-resolved metabolic imaging techniques, that is, NAD(P)H-FLIM, are complemented by real-time NMR, paving the way toward a comprehensive spatiotemporal understanding of metabolic pathways in living cells."

Journal • Hematological Malignancies • Lymphoma • Oncology • NAMPT

Interplay of PRMTs and Identification of Biomarkers Through Machine Learning Algorithms in Pan-Cancer, Highlighting PRMT3 as a Biomarker in Pancreatic Cancer. (PubMed, FASEB J) - "Daporinad, dinaciclib, and sepantronium bromide were predicted as potential drugs for the majority of cancer types. Potential biomarkers had been identified that may predict responses to immunotherapy and improve survival outcomes for cancer patients. This study provided a detailed overview of the functional roles, genetic and epigenetic alterations, and prognostic significance of PRMTs in pan-cancer."

Biomarker • IO biomarker • Journal • Pan tumor • Oncology • Pancreatic Cancer • Solid Tumor • PRMT3

Visfatin Promotes Renal Cell Carcinoma Progression: Evidence from Clinical Samples and Cell Line Models. (PubMed, J Kidney Cancer VHL) - "Conversely, the addition of FK866, a visfatin inhibitor, suppressed cell proliferation and reduced these proteins. Our findings suggest that visfatin from peri-tumor adipose tissue influences the malignancy of RCC and plays a role in promoting the growth of RCC. This indicates a potential mechanism by which adipose tissue contributes to the progression of RCC, providing a possible target for therapeutic intervention."

Journal • Preclinical • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • HIF1A • NAMPT