Description

5-Amino-1MQ – Technical Biochemical Mechanism Profile

(Small-molecule NNMT inhibitor; NAD⁺/SAM pathway modulator – research use only)

5-Amino-1MQ is a small-molecule inhibitor of Nicotine Amide N-Methyltransferase (NNMT), an enzyme that catalyzes the methylation of nicotinamide to form 1-methylnicotinamide (MNA) using S-adenosyl-methionine (SAM) as a methyl donor.
Inhibition of NNMT alters NAD⁺ salvage, SAM availability, methyl donor balance, and downstream transcriptional programs linked to cellular metabolism.

✅ 1. Primary Molecular Target

NNMT (Nicotinamide N-Methyltransferase)

• Cytosolic enzyme regulating nicotinamide → 1-methylnicotinamide

• Consumes SAM and produces S-adenosylhomocysteine (SAH)

5-Amino-1MQ binding results in:

• Reduced formation of MNA

• Increased intracellular nicotinamide

• Preservation of SAM pools

• Enhanced NAD⁺ salvage pathway flux

✅ 2. Core Metabolic Pathways Affected

A. NAD⁺ Salvage Pathway

With NNMT suppressed, more nicotinamide enters:

• NAMPT → NMNAT → NAD⁺ synthesis

In vitro models demonstrate:

• ↑ NAMPT activity

• ↑ NAD⁺ availability

• Potential shifts in SIRT-dependent transcription

Key enzyme targets measured:

• NAMPT

• NMNAT1–3

• SIRT1 / SIRT3 (NAD⁺-dependent deacetylases)

B. SAM/SAH & Methyl Donor Balance

By reducing NNMT activity:

• SAM is preserved

• SAH formation decreases

• Impacts cellular methylation potential

This shifts histone and DNA methylation status in research cultures.

Gene classes affected:

• Chromatin modulators (DNMT1, EZH2)

• Metabolic regulators (PPARG, SREBF1)

C. AMPK / SIRT Crosstalk

Increased NAD⁺ availability can influence:

• SIRT1 → PGC-1α activation

• AMPK phosphorylation

These pathways regulate mitochondrial and metabolic genes.

Representative downstream genes:

• PPARGC1A (PGC-1α)

• NRF1

• TFAM

• CPT1B, ACADL (fatty-acid oxidation)

✅ 3. Secondary Signaling Pathways

✅ 4. Representative Gene Targets

✅ 5. Key Enzymes Affected

✅ Second Messengers

✅ Mechanistic Summary

• 5-Amino-1MQ inhibits NNMT

• Lowers conversion of nicotinamide → MNA

• Preserves SAM and supports NAD⁺ salvage

• Modulates SIRT1/AMPK/PGC-1α signaling

• Alters transcription of metabolic, chromatin, and stress-response genes

Research-Only Classification

5-Amino-1MQ is supplied exclusively for controlled in-vitro laboratory research.
Not approved for human or animal administration, therapeutic use, or any biological application outside research environments.