Restoration of viral replication by NAD+ precursors in the presence of 6-AN or suppression of replication by the NAMPT inhibitor FK866 suggested NAD+ availability as a critical determinant of VSV replication...Collectively, these findings demonstrate that VSV replication is tightly coupled to metabolic programs, particularly those governing energy production and NAD(P)H balance. This work provides a metabolic framework for optimizing oncolytic VSV therapies and suggests that metabolic interventions in cancer treatment may influence oncolytic virus efficacy.

P1, N=24, Recruiting, Remedy Plan, Inc. | Not yet recruiting --> Recruiting | N=18 --> 24

We recently completed a clinical trial in dogs with DLBCL using a combination of canine anti-CD20 antibody and low dose doxorubicin followed by one of three small molecule immune-modulating agents (KPT-9274, TAK-981 or RV1001). To facilitate point-of-care PBMC gene expression testing that could be used to distinguish those dogs likely to require more intensive treatment regimens in advance of relapse, we developed qPCR assays for TBHD, NPNT and ISG20. Together these data provide proof of principle that biomarker interrogation in PBMCs can help predict early relapse and poor responders to inform clinical management of DLBCL.

The MTD of KPT-9274 was not reached in a dose escalation study conducted in patients with advanced solid tumors. Clinical activity was not observed at study doses in combination with niacin or nivolumab. Further investigation into potential therapeutic areas where KPT-9274 may serve as a targeted agent is warranted.

Our data demonstrate that the enhanced MTFP1 expression leads to an upregulated glutamine-OXPHOS axis in PDAC liver colonisation. This metabolic shift is triggered by the ROS/PI3K/AKT/c-MYC/SLC1A5 pathway. Targeting MTFP1 may be a potential therapeutic strategy for PDAC patients with liver metastasis.

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.

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.

P1, N=16, Completed, University of Colorado, Denver | Active, not recruiting --> Completed | N=40 --> 16 | Trial completion date: Feb 2027 --> Oct 2025

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.

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.

The NAMPT inhibitor KPT-9274 reduced viability and induced apoptosis in MCL cells irrespective of TP53 status...Our findings establish NAMPT as a dual-context therapeutic node, providing a precision medicine framework to circumvent chemoresistance in high-risk MCL. These results advocate for the clinical evaluation of TP53 status-guided NAMPT inhibitor combinations to address this unmet oncologic challenge.

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.