5-Amino-1MQ

5-Amino-1MQ (5-amino-1-methylquinolinium) is a small-molecule inhibitor of nicotinamide N-methyltransferase (NNMT), the cytosolic enzyme that transfers a methyl group from S-adenosylmethionine (SAM) to nicotinamide. It is a quinolinium cation, not a peptide, and it came out of a structure-activity study in which methylated quinoliniums inhibited NNMT at concentrations near 1 micromolar (Neelakantan et al., 2017).

Interest in the target followed a mouse study in which knocking down NNMT in fat and liver protected against diet-induced obesity and raised adipose SAM and NAD+ (Kraus et al., 2014). The published work is enzyme, cell culture and rodent research; no human studies appear in PubMed.

Published work on 5-Amino-1MQ falls into six areas. Each summary below states the model used. Most of it comes from one group at the University of Texas Medical Branch and from Ridgeline Therapeutics, a company founded by that group's senior author; several of the later papers disclose that relationship. Independent work is limited to cancer models.

Enzyme inhibition and selectivity

Docking to the nicotinamide pocket of NNMT tracked measured IC50 values across the inhibitor series (Neelakantan et al., 2017), and a follow-up paper carried 5-Amino-1MQ, with an IC50 of about 1.2 micromolar, into selectivity, cell and mouse studies.

It crossed artificial membranes and Caco-2 cell monolayers readily, with no efflux, and at the highest concentrations tested (100 to 600 micromolar, depending on the enzyme) it did not meaningfully inhibit the related methyltransferases DNMT1, PRMT3 and COMT or the NAD+ salvage enzymes NAMPT and SIRT1 (Neelakantan et al., 2018). Models: purified enzyme assays, computational docking and Caco-2 cell culture.

Adipocyte metabolism

In differentiated 3T3-L1 adipocytes, 5-Amino-1MQ lowered intracellular 1-methylnicotinamide, the product of the NNMT reaction, and raised NAD+ about 1.2 to 1.6 fold and SAM; in differentiating cells it reduced lipid accumulation. Viability of 3T3-L1 preadipocytes was unchanged at 10 micromolar, with modest cytotoxicity at 100 to 300 micromolar (Neelakantan et al., 2018). Model: mouse adipocyte cell line.

Diet-induced obese mice

In the same paper, male diet-induced obese C57BL/6 mice given the compound for 11 days lost about 5 percent of baseline body weight while controls gained about 1 percent, with no difference in food intake, and epididymal fat mass fell about 35 percent (Neelakantan et al., 2018). A 28-day study in the same model reported smaller gains in body weight and fat mass, better glucose tolerance and insulin sensitivity, and less hepatic steatosis (Babula et al., 2024).

In obese mice switched to a lean diet, adding the inhibitor brought body composition and liver fat to the levels of lean controls faster than the diet switch alone (Sampson et al., 2021) and produced a distinct cecal microbiome pattern (Dimet-Wiley et al., 2022). Model: mouse.

Aged skeletal muscle

In 24-month-old mice with a chemically induced muscle injury, the inhibitor increased muscle stem cell proliferation and fusion, gave nearly twice the myofiber cross-sectional area of controls and raised peak torque by about 70 percent; in C2C12 myoblasts it promoted differentiation (Neelakantan et al., 2019). In mice treated from 22 to 24 months of age, sedentary animals on the inhibitor had about 40 percent greater grip strength than sedentary controls, against about 20 percent for exercise alone and about 60 percent for both combined (Dimet-Wiley et al., 2024). Models: mouse and mouse myoblast cell line.

Cancer cell and tumor models

Outside groups have used it as an NNMT tool compound in oncology. It reduced proliferation of HeLa cervical cancer cells, with lower phospho-Akt and SIRT1 protein and no apparent effect on HEK-293 cells (Akar et al., 2021). In mouse models of urothelial bladder cancer, the iodide salt reduced tumor growth and enhanced the effect of an anti-PD-L1 antibody, in a study linking NNMT in cancer-associated fibroblasts to immunotherapy resistance (Yang et al., 2024).

In osteosarcoma and Merkel cell carcinoma lines it was one of three NNMT inhibitors that lowered viability, raised reactive oxygen species and activated apoptotic pathways (Pompei et al., 2025). Models: human cancer cell lines and mouse tumor models.

Measurement and pharmacokinetics

A validated LC-MS/MS method quantifies the compound in rat plasma and urine from 10 to 2,500 ng/mL by monitoring the intact cation at m/z 159.1. Applied to a rat pharmacokinetic study, it gave terminal half-lives of roughly 4 to 7 hours depending on the route compared (Awosemo et al., 2021). Model: rat.