5-Amino-1MQ: Safety Profile & Research Summary

Preclinical Animal Studies

• Obesity — DIO Mice (Neelakantan 2018): 20 mg/kg SC 3×/day, 11 days. -5.1% body weight (P<0.0001 at day 10), -35% WAT mass (P<0.001), >30% decreased adipocyte size and >40% decreased volume (P<0.05), ~30% lower plasma cholesterol (P<0.05). No change in food intake; no adverse toxicity. [2]
• Obesity + Diet (Sampson 2021): 32 mg/kg SC daily, ~7 weeks (DIO mice switched to lean diet). -29.3% fat mass from baseline vs. -2.9% for diet alone. Body composition normalized to lean controls. Metabolomic analysis predicted lipid synthesis inhibition (z-score = -2.566, P=0.045). [9]
• Microbiome (Dimet-Wiley 2022): 32 mg/kg SC daily, ~7 weeks. Treated mice showed distinct microbiome cluster with increased Lactobacillus and Parasutterella; decreased Erysipelatoclostridium. [15]
• Metabolic/Liver (Babula 2024): Daily SC, 28 days (DIO mice). Normalized ALT/AST, improved oral glucose tolerance, suppressed hyperinsulinemia, reduced liver weight and triglycerides, attenuated steatosis and macrophage infiltration. [12]
• Exercise Mimicry (Dimet-Wiley 2024): 10 mg/kg SC daily, 8 weeks (aged 22-month mice). Sedentary treated: +40% grip strength (P<0.001). Exercise + treated: +60% grip strength, maintained 1.8 km/day running increase at week 8 (P=0.0039). >30% reduction in intramyocellular lipid. [10]
• Muscle Regeneration (Neelakantan 2019): 5–10 mg/kg, 1–3 weeks (aged 24-month mice with acute injury). ~2× myofiber CSA, +70% peak torque (P<0.05), increased MuSC proliferation and fusion. [11]
• Peripheral Artery Disease (Dong 2025): Daily dosing (BALB/cJ mice with hindlimb ischemia). Significantly improved muscle strength (P<0.0001), power (P=0.031), total work (P=0.037). Independent of perfusion or capillary changes. [16]

Pharmacokinetic Profile (Rats)

Awosemo/Neelakantan et al. (2021): Oral bioavailability 38.4%; T½ 6.9h (oral) / 3.8h (IV); Cmax 2,252 ng/mL. High membrane permeability. No 24-hour accumulation in heart, liver, kidney, or brain (recirculation noted at ~12h). Cross-species liver metabolic stability confirmed. [7]

reported tolerability profile (Preclinical)

Acute Toxicity: In mice, animals survived doses from 50 mg/kg to 2,000–5,000 mg/kg with no observable adverse reactions during 48-hour monitoring. [2]

Subacute Toxicity (14 days): Liver (AST, GGT), heart (troponin I), and inflammatory (CRP) markers were unaffected except for significant CRP rise at highest IV dose (200 mg/kg) at 6 hours post-dose. [2]

Cell Viability: No impact up to 100 µM; modest cytotoxicity at 100–300 µM; ~40% cytotoxicity at 600 µM in 3T3-L1 adipocytes. [1]

Clinical Development Status

Ridgeline Therapeutics (founded by Dr. Watowich) is developing a lead NNMT inhibitor candidate (RT-002), conducting IND-enabling GLP toxicology studies in minipigs with the goal of submitting an IND briefing package to the FDA for Phase 1 first-in-human clinical trials. [6]