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% peso corporal (P<0.0001 at day 10), -35% WAT mass (P<0.001), >30% diminuiu adipocito size and >40% diminuiu 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% massa gorda em relacao ao basal vs. -2.9% for diet alone. Body composition normalized to lean controls. Metabolomic analysis predicted lipid synthesis inibicao (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 aumentou Lactobacillus and Parasutterella; diminuiu Erysipelatoclostridium. [15]
• Metabolic/Liver (Babula 2024): Daily SC, 28 days (DIO mice). Normalized ALT/AST, melhorou oral glucose tolerance, suprimiu hyperinsulinemia, reduziu liver weight and triglycerides, atenuou steatosis and macrofago 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, manteve 1.8 km/day running increase na semana 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 agudo(a) injury). ~2× myofiber CSA, +70% peak torque (P<0.05), aumentou MuSC proliferacao and fusion. [11]
• Peripheral Artery Disease (Dong 2025): Daily dosing (BALB/cJ mice with hindlimb isquemia). Significantly melhorou muscle strength (P<0.0001), power (P=0.031), total work (P=0.037). Independent of perfusao or capillary changes. [16]

Pharmacokinetic Profile (Rats)

Awosemo/Neelakantan et al. (2021): Oral biodisponibilidade 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 observado(a) at ~12h). Cross-species liver metabolic stability confirmou. [7]

relatado(a) perfil de tolerabilidade (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 adipocitos. [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 com o(a) goal of submitting an IND briefing package para o(a) FDA for Phase 1 first-in-human ensaios clinicos. [6]