K4 Elite
K4 Elite
5-Amino-1-methylquinolinium (5-amino-1MQ, 5A1MQ, 5-AMQ) is a small-molecule, membrane-permeable inhibitor of nicotinamide N-methyltransferase (NNMT) developed at the University of Texas Medical Branch (Watowich, Neelakantan and colleagues). All published efficacy and safety data come from cell culture and rodent models: diet-induced obese mice (Neelakantan et al., 2018; Sampson et al., 2021; Babula et al., 2024), aged mice with muscle injury or sarcopenia (Neelakantan et al., 2019; Dimet-Wiley et al., 2024), rat pharmacokinetics (Awosemo et al., 2021), and mouse tumour models. No human clinical trial of 5-amino-1MQ has been published or registered, and reviews of NNMT inhibition note that no clinical trials targeting NNMT have been reported. Adverse-effect information below is therefore limited to animal and in-vitro observations.
Each row records what a published study did: who it enrolled, the regimen it administered to those subjects, and what it reported. These are historical study descriptions, not protocols to follow.
| Study | Population | Regimen as reported | Primary findings |
|---|---|---|---|
| Neelakantan et al., Biochem Pharmacol 2018 (mouse diet-induced obesity; in-vitro adipocytes) | Diet-induced obese mice on a high-fat diet; cultured adipocytes; Caco-2 and PAMPA permeability assays | Diet-induced obese mice were treated systemically with a potent methylquinolinium NNMT inhibitor; in vitro, adipocytes were exposed to NNMT inhibitors and intracellular 1-MNA, NAD+ and SAM were measured. | Treated mice showed significantly reduced body weight, white adipose mass, adipocyte size and plasma total cholesterol without change in total food intake; in adipocytes the inhibitors lowered 1-MNA, raised NAD+ and SAM and suppressed lipogenesis. The authors reported no observable adverse effects. |
| Neelakantan et al., Biochem Pharmacol 2019 (aged-mouse muscle injury model) | 24-month-old mice with barium chloride-induced tibialis anterior injury; C2C12 myoblasts in vitro | Mice were treated with saline or NNMT inhibitor at 5 or 10 mg/kg for 1 week post-injury, or control versus 10 mg/kg for 3 weeks post-injury. | Muscle stem cell proliferation and fusion increased, myofibre cross-sectional area was nearly 2-fold greater, and tibialis anterior peak torque was about 70% higher in treated mice than controls. |
| Sampson et al., Sci Rep 2021 (mouse diet-induced obesity with diet switch) | Diet-induced obese mice switched to a lean diet | Obese mice were switched to a lean diet with or without concurrent NNMT inhibitor treatment. | Combined treatment accelerated body-weight and fat loss, increased lean-mass ratio, reduced liver and epididymal fat weights and improved hepatic steatosis relative to diet switch alone, normalising body composition to lean controls. |
| Babula et al., Diabetes Obes Metab 2024 (mouse diet-induced obesity; mouse PK) | Diet-induced obese mice; age- and strain-matched mice for pharmacokinetics | DIO mice were administered vehicle or 5A1MQ once daily for 28 days; pharmacokinetics were established after intravenous, oral and subcutaneous dosing. | 5A1MQ dose-dependently limited body-weight and fat-mass gain, improved oral glucose tolerance and insulin sensitivity, suppressed hyperinsulinaemia, attenuated hepatic steatosis and macrophage infiltration, and normalised ALT, AST and ketone bodies; subcutaneous dosing gave high systemic exposure with distribution to adipose, muscle and liver. |
| Dimet-Wiley et al., Sci Rep 2024 (aged-mouse sarcopenia model) | Aged (22-24-month-old) mice, sedentary or exercised | Mice were treated from 22 to 24 months of age with NNMT inhibitor, intensive exercise, or both. | Treated sedentary mice had about 40% greater grip strength than sedentary controls (exercise alone: 20%); the combination gave a 60% increase, with reduced intramyocellular lipid. |
| Awosemo et al., J Pharm Biomed Anal 2021 (rat pharmacokinetics) | Rats | Rats received 5-AMQ intravenously or orally; plasma and urine were analysed by a validated LC-MS/MS assay. | 5-AMQ showed substantial plasma exposure by both routes, with a mean oral Cmax of 2252 ng/mL, AUC of 3708 (IV) and 14431 (oral) h·ng/mL, and a terminal half-life of about 3.8 h. |
Effects recorded in the cited reports. Frequencies are those the source reported, in the population that source studied.
| Effect | Frequency / context | Source |
|---|---|---|
| No observable adverse effects (animal data) | In diet-induced obese mice, systemic NNMT-inhibitor treatment did not affect total food intake and the authors reported no observable adverse effects (Neelakantan et al., 2018). No formal toxicology study has been published. | Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice ↗ |
| Anti-proliferative / pro-apoptotic activity in cancer cell lines (in vitro) | 5-methylquinolinium NNMT inhibitor at 0.1-500 µM inhibited HeLa cervical cancer cell proliferation with morphological signs of apoptosis, without apparent effect on HEK-293 cells (Akar et al., 2021; in vitro only). | Small molecule inhibitor of nicotinamide N-methyltransferase shows anti-proliferative activity in HeLa cells ↗ |
| Altered gut microbiome composition (mouse) | NNMT-inhibitor-treated DIO mice switched to a low-fat diet showed a distinct caecal microbiome pattern (decreased Erysipelatoclostridium, increased Lactobacillus) versus vehicle (Dimet-Wiley et al., 2022). | Reduced calorie diet combined with NNMT inhibition establishes a distinct microbiome in DIO mice ↗ |
| Human safety data | None. No human trial of 5-amino-1MQ has been published; reviews of NNMT as a therapeutic target state that clinical trials targeting NNMT have not been reported (Liu et al., 2021; Sun et al., 2024). | Roles of Nicotinamide N-Methyltransferase in Obesity and Type 2 Diabetes ↗ |
No interactions with a verifiable citation have been indexed for this compound.
Exclusions and label contraindications recorded in the cited sources.