Small Molecule Inhibitors of Nicotinamide N-Methyltransferase Enzyme for the Treatment of Osteosarcoma and Merkel Cell Carcinoma: Potential for the Development of a Targeted Therapeutic Strategy.

Pompei V, Cecati M, Serritelli EN, Gerini E, Campagna R, Pozzi V, Van Haren MJ, Martin NI, Emanuelli M, Sartini D

Biomolecules5 Nov 2025Cited by 2 (Europe PMC)

PMID41301471PMCIDPMC12650368DOI10.3390/biom15111553PepBankPUB-41301471

Summary

Nicotinamide N-methyltransferase (NNMT) enzyme catalyzes the N-methylation of nicotinamide and its overexpression has been reported in many neoplasms, favoring traits featuring an aggressive tumor cell phenotype. Our recent data demonstrated that NNMT upregulation in osteosarcoma (OS) and Merkel cell carcinoma (MCC) led to a significant increase in cell proliferation and migration ability, together with a reduction in sensitivity to chemotherapeutic treatment. Based on these findings, we investigated the impact of small molecule NNMT inhibitors 5-amino-1-methyl quinolinium (5-AMQ), 6-methoxynicotinamide (6MeONa) and Eli Lilly's pyrimidine 5-carboxamide (EL-1) on U-2 OS and Saos-2 OS cell lines and MCC13 and MCC26 MCC cell lines. Following incubation of the cells with these compounds, cell viability, reactive oxygen species (ROS) production and apoptosis induction were evaluated. Cells were then subjected to combined treatment with inhibitors and cisplatin (CDDP), and viability and ROS levels were further analyzed. Our results clearly illustrate that cells treated with NNMT inhibitors underwent significant reductions in viability, increased ROS production and activation of apoptotic pathways. Given the association of NNMT with cancer aggressiveness, inhibiting its catalytic activity might present a novel strategy for counteracting cancer growth and chemoresistance, providing the rationale for an effective anti-cancer therapy based on the use of specific NNMT inhibitors.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone3

In this study, 5-amino-1MQ was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking 5-amino-1MQ.

01LabNot a test of 5-amino-1MQ aloneIn vitro (cells)Efficacy outcome
In osteosarcoma and Merkel cell carcinoma cells, NNMT inhibitor treatments significantly reduced viability.
In plain wordsIn cells, NNMT inhibitor treatments significantly reduced cancer cell viability.
Peptide
5-amino-1MQ
Outcome
DecreaseCell viability
Study
n: not reported in source
U-2 OS, Saos-2, MCC13 and MCC26 cells
Outcome group
Tumor growth · Cancer
Source sentences
Summary
Our results clearly illustrate that cells treated with NNMT inhibitors underwent significant reductions in viability, increased ROS production and activation of apoptotic pathways.
1 context sentence(design, population, supporting numbers)
Summary · context
Based on these findings, we investigated the impact of small molecule NNMT inhibitors 5-amino-1-methyl quinolinium (5-AMQ), 6-methoxynicotinamide (6MeONa) and Eli Lilly's pyrimidine 5-carboxamide (EL-1) on U-2 OS and Saos-2 OS cell lines and MCC13 and MCC26 MCC cell lines.
In this study, 5-amino-1MQ was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking 5-amino-1MQ.
Show in the study text Report a problemFND-4130147101
02LabNot a test of 5-amino-1MQ aloneIn vitro (cells)Efficacy outcome
In osteosarcoma and Merkel cell carcinoma cells, NNMT inhibitor treatments increased ROS production.
In plain wordsIn cells, NNMT inhibitor treatments increased ROS production.
Peptide
5-amino-1MQ
Outcome
IncreaseROS production
Study
n: not reported in source
U-2 OS, Saos-2, MCC13 and MCC26 cells
Outcome group
Tumor growth · Cancer
Source sentences
Summary
Our results clearly illustrate that cells treated with NNMT inhibitors underwent significant reductions in viability, increased ROS production and activation of apoptotic pathways.
1 context sentence(design, population, supporting numbers)
Summary · context
Based on these findings, we investigated the impact of small molecule NNMT inhibitors 5-amino-1-methyl quinolinium (5-AMQ), 6-methoxynicotinamide (6MeONa) and Eli Lilly's pyrimidine 5-carboxamide (EL-1) on U-2 OS and Saos-2 OS cell lines and MCC13 and MCC26 MCC cell lines.
In this study, 5-amino-1MQ was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking 5-amino-1MQ.
Show in the study text Report a problemFND-4130147102
03LabNot a test of 5-amino-1MQ aloneIn vitro (cells)Efficacy outcome
In osteosarcoma and Merkel cell carcinoma cells, NNMT inhibitor treatments activated apoptotic pathways.
In plain wordsIn cells, NNMT inhibitor treatments activated pathways for cell death.
Peptide
5-amino-1MQ
Outcome
IncreaseApoptotic pathway activation
Study
n: not reported in source
U-2 OS, Saos-2, MCC13 and MCC26 cells
Outcome group
Tumor growth · Cancer
Source sentences
Summary
Our results clearly illustrate that cells treated with NNMT inhibitors underwent significant reductions in viability, increased ROS production and activation of apoptotic pathways.
1 context sentence(design, population, supporting numbers)
Summary · context
Based on these findings, we investigated the impact of small molecule NNMT inhibitors 5-amino-1-methyl quinolinium (5-AMQ), 6-methoxynicotinamide (6MeONa) and Eli Lilly's pyrimidine 5-carboxamide (EL-1) on U-2 OS and Saos-2 OS cell lines and MCC13 and MCC26 MCC cell lines.
In this study, 5-amino-1MQ was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking 5-amino-1MQ.
Show in the study text Report a problemFND-4130147103

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
14 Oct 2026, 05:02 UTC
Study results updated
Version 1
14 Oct 2026, 01:46 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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