Informational only. Not medical advice.INFORMATIONAL PLATFORM ONLY — NOT MEDICAL ADVICE, DIAGNOSIS, OR TREATMENT
Informational only. Not medical advice.INFORMATIONAL PLATFORM ONLY — NOT MEDICAL ADVICE, DIAGNOSIS, OR TREATMENT
Head-to-head comparison of CMS121 and NSI-189 — mechanism, dosing, side effects, legal status, and pricing.
CMS121 is a non-peptide small-molecule quinoline, a synthetic analog of the natural flavonoid fisetin, developed to inhibit fatty acid synthase (FASN) and reduce lipid peroxidation in neuronal cells. It has completed a Phase 1 safety and pharmacokinetics trial in healthy volunteers (NCT05318040) but has no approved medical use and no published human efficacy data in Alzheimer's disease or any other condition. The compound is sold by research-chemical suppliers for laboratory use only; some direct-to-consumer vendors incorrectly market it as a "peptide" supplement despite its small-molecule structure.
NSI-189 (INN: amdiglurax; developmental code ALTO-100) is a non-peptide small-molecule benzylpiperazine-aminopyridine derivative investigated as a neurogenic/neuroplasticity-modulating agent for major depressive disorder. It stimulates hippocampal neural progenitor proliferation and differentiation in vitro and neurogenesis in vivo (mouse), acting independently of monoamine reuptake pathways. NSI-189 has never been FDA-approved; Phase 2 monotherapy trials in MDD (220 patients, 2020) and a Phase 2b trial under Alto Neuroscience (~300 patients, 2024) both failed to meet primary MADRS endpoints, and it remains investigational only.
CMS121
NSI-189
Category
Legal Status
Mechanism
Dose Range
Route
COA-verified vendors · trust score ≥70 required · single-vial price — bulk/bundle deals may be lower
CMS121
NSI-189
No pricing data yet.
Check NSI-189 prices →COA corpus from Disclosed Labs — independently tested batches only.
CMS121
3
COAs
99.1%
Avg purity
2
Labs
NSI-189
No COA data yet.
Submit testing data →In APPswe/PS1dE9 double-transgenic mice (a model of Alzheimer's disease), dietary CMS121 (~34 mg/kg/day for 3 months starting at 9 months of age) normalized elevated hippocampal 4-HNE lipid-peroxidation adducts to wild-type levels, reduced 15-LOX2 and GFAP expression, and reversed cognitive deficits in Morris water maze testing to performance indistinguishable from wild-type mice. In vitro, CMS121 reduced iNOS, COX2, and TNF-α induction and blunted lipid-peroxidation increases in LPS-activated microglial cell cultures. A completed Phase 1 trial in approximately 100 healthy volunteers (NCT05318040) tested single oral doses up to 1800 mg and repeat doses up to 900 mg/day in young adults (600 mg/day in elderly subjects) for 7 days, reporting generally well-tolerated safety profiles with the majority of adverse events classified as mild; no serious adverse events were reported. Elderly subjects showed higher systemic exposure and longer terminal half-life than young adults, and fed-state exposure was approximately 50% higher than fasted with delayed absorption. No human efficacy data exist in Alzheimer's disease patients or any patient population.
Key references
Human data exist from three registered trials: a Phase 1 single-dose PK study in healthy volunteers (NCT01310881), a Phase 1B multiple-dose-escalation study in 24 MDD patients (28-day inpatient dosing at 40 mg once/twice/thrice daily; half-life ~17.4–20.5 hours; no serious adverse events; no significant hippocampal volume change at day 28 or 84), and a Phase 2 double-blind, placebo-controlled trial in 220 MDD outpatients (12 weeks at 40 mg or 80 mg daily) that missed its primary MADRS endpoint at both doses (p=0.22 and p=0.34, respectively), with some significant secondary/patient-reported benefits at 40 mg. A Phase 2b trial under the ALTO-100 designation (~300 adults, 34 US sites, 6-week double-blind) also failed to meet its primary MADRS endpoint (topline October 2024). Preclinical findings include improved motor/neurological deficits sustained to 24 weeks in a rat stroke model (oral dosing starting 6 hours post-MCAO; increased hippocampal/cortical MAP2 neurite outgrowth; in vitro OGD/R assays showed reduced cell death and upregulated BDNF/SCF), reversal of motor and cognitive impairments in an Angelman syndrome mouse model (with mild performance enhancement in wild-type mice), improved Barnes maze memory retention in a 5xFAD Alzheimer's mouse model (conference abstract), and prevention of peripheral neuropathy indices with increased hippocampal neurogenesis/synaptic markers/volume and protected long-term memory in mouse and rat models of type 1 and type 2 diabetes, alongside enhanced mitochondrial function in a type 2 diabetic rat model.
CMS121 and NSI-189 are both in the Cognitive category and may have overlapping mechanisms. Researchers should review both profiles carefully, understand the mechanisms of action, and monitor the relevant biomarkers when combining compounds in the same class. As always, consult a licensed healthcare provider before making any decisions about combining research compounds.
This platform provides informational tools only, not medical advice. This comparison is for educational purposes only. Consult a licensed provider.
Frequency
Dosing Notes
Side Effects
Contraindications
Lab Testing
Key references
Disclosed Labs