Pharmacological profiling of intravenous MP-04: sustained NAD⁺ augmentation, immune modulation, and renal protection in preclinical models.

Ghosh A, Pranesh G, Zachariah N, Murakami E, Heredia A, Mathur P, Burns-Naas LA, Weng S, Ramanathan A, Kottilil S, Subramanian GM

Frontiers in pharmacology10 Jun 2026

PMID42358367PMCIDPMC13291046DOI10.3389/fphar.2026.1832979PepBankPUB-42358367

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Summary

IntroductionSystemic inflammation and mitochondrial bioenergetic failure are central drivers of multi-organ dysfunction in advanced liver disease, sepsis, and acute kidney injury (AKI). Currently available therapies remain largely supportive and fail to directly address intracellular NAD⁺ depletion and immune-metabolic dysregulation. We investigated MP-04, a novel intravenous formulation of dihydronicotinamide riboside (NRH), for its ability to restore NAD⁺ homeostasis, modulate immune metabolism, and confer organ protection in relevant preclinical models.MethodsThe NAD⁺-enhancement activity of nicotinamide riboside (NR) and MP-04 was evaluated in human hepatoma (HepG2), T-cell (Jurkat), kidney (HEK293) cell lines, and peripheral blood mononuclear cells (PBMCs). Cellular bioenergetics were assessed using Seahorse extracellular flux analysis. Immunomodulatory effects were examined in polyclonally activated human PBMCs and in a murine endotoxin-induced systemic inflammation model. Pharmacokinetics and pharmacodynamics were assessed following intravenous (IV) dosing in rats, and organ protection was evaluated in a cisplatin-induced AKI mouse model. Safety of MP-04 was evaluated in rat and dog Good Laboratory Practice (GLP) toxicology studies.ResultsMP-04 produced rapid, distinct, and dose-dependent increases in intracellular NAD⁺ across all tested human cell types and was markedly more potent than NR. IV administration in rats resulted in sustained elevations of NAD⁺ and NADH in blood, liver, and kidney that persisted beyond the systemic clearance of MP-04, with strong correlations between blood and tissue NAD⁺ levels. In activated immune cells, MP-04 reduced reliance on aerobic glycolysis, and significantly attenuated pro-inflammatory cytokine production without affecting resting cells. In vivo, MP-04 reduced systemic inflammatory cytokines following endotoxin challenge and conferred significant biochemical and histological protection against cisplatin-induced AKI. MP-04 was safe and well tolerated in rat and dog following once daily IV administration for 7 days.ConclusionMP-04 is a safe and highly potent intravenous NAD⁺ precursor that modulates cellular metabolism, reduces maladaptive immune activation, and protects against inflammation-associated organ injury in preclinical models. These findings support MP-04 as a promising metabolic-immunomodulatory therapeutic strategy for conditions characterized by systemic inflammation and organ failure, including hepatorenal syndrome-associated AKI, beyond the limits of current supportive care.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

No result from this study comes from a test of the peptide.

Natural levels measured5

These results measure the body's own peptide. Nobody was given the peptide. They are not evidence about taking it. They are left out of key results, evidence counts and charts.

01AnimalEndogenous levelAnimal study (in vivo)Other
In rats, MP-04 produced sustained elevations of natural blood NAD+ beyond systemic MP-04 clearance.
In plain wordsIn rats, MP-04 increased natural blood NAD+ levels beyond the drug's clearance.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
IncreaseBlood NAD+
Study
ratn: not reported in source
intravenous MP-04 dosing
Outcome group
Pharmacokinetics · Pharmacology
Source sentences
Summary
IV administration in rats resulted in sustained elevations of NAD⁺ and NADH in blood, liver, and kidney that persisted beyond the systemic clearance of MP-04, with strong correlations between blood and tissue NAD⁺ levels.
This result measures the body's own NAD+ (nicotinamide adenine dinucleotide). Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4235836702
02AnimalEndogenous levelAnimal study (in vivo)Other
In rats, MP-04 produced sustained elevations of natural liver NAD+ beyond systemic MP-04 clearance.
In plain wordsIn rats, MP-04 increased natural liver NAD+ levels beyond the drug's clearance.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
IncreaseLiver NAD+
Study
ratn: not reported in source
intravenous MP-04 dosing
Outcome group
Pharmacokinetics · Pharmacology
Source sentences
Summary
IV administration in rats resulted in sustained elevations of NAD⁺ and NADH in blood, liver, and kidney that persisted beyond the systemic clearance of MP-04, with strong correlations between blood and tissue NAD⁺ levels.
This result measures the body's own NAD+ (nicotinamide adenine dinucleotide). Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4235836703
03AnimalEndogenous levelAnimal study (in vivo)Other
In rats, MP-04 produced sustained elevations of natural kidney NAD+ beyond systemic MP-04 clearance.
In plain wordsIn rats, MP-04 increased natural kidney NAD+ levels beyond the drug's clearance.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
IncreaseKidney NAD+
Study
ratn: not reported in source
intravenous MP-04 dosing
Outcome group
Pharmacokinetics · Pharmacology
Source sentences
Summary
IV administration in rats resulted in sustained elevations of NAD⁺ and NADH in blood, liver, and kidney that persisted beyond the systemic clearance of MP-04, with strong correlations between blood and tissue NAD⁺ levels.
This result measures the body's own NAD+ (nicotinamide adenine dinucleotide). Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4235836704
04AnimalEndogenous levelAnimal study (in vivo)Other
In rats receiving MP-04, blood and tissue NAD+ levels showed strong correlations.
In plain wordsIn rats receiving MP-04, natural blood and tissue NAD+ levels were strongly linked.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
Not applicableBlood-tissue NAD+ correlation
Study
ratn: not reported in source
intravenous MP-04 dosing
Outcome group
Pharmacokinetics · Pharmacology
Source sentences
Summary
IV administration in rats resulted in sustained elevations of NAD⁺ and NADH in blood, liver, and kidney that persisted beyond the systemic clearance of MP-04, with strong correlations between blood and tissue NAD⁺ levels.
This result measures the body's own NAD+ (nicotinamide adenine dinucleotide). Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4235836705
05LabEndogenous levelIn vitro (cells)Other
In tested human cells, MP-04 increased intracellular NAD+ in a rapid dose-dependent manner and was more potent than NR.
In plain wordsIn human cells, MP-04 increased natural NAD+ levels more potently than NR.
Peptide
NAD+ (nicotinamide adenine dinucleotide)
Outcome
IncreaseIntracellular NAD+
Study
humann: not reported in source
HepG2, Jurkat, HEK293 and PBMCs
Comparator
NR
Outcome group
Pharmacokinetics · Pharmacology
Source sentences
Summary
MP-04 produced rapid, distinct, and dose-dependent increases in intracellular NAD⁺ across all tested human cell types and was markedly more potent than NR.
1 context sentence(design, population, supporting numbers)
Summary · context
The NAD⁺-enhancement activity of nicotinamide riboside (NR) and MP-04 was evaluated in human hepatoma (HepG2), T-cell (Jurkat), kidney (HEK293) cell lines, and peripheral blood mononuclear cells (PBMCs).
This result measures the body's own NAD+ (nicotinamide adenine dinucleotide). Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4235836701

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Version 2Current
14 Oct 2026, 05:02 UTC
Study results updated
Version 1
14 Oct 2026, 01:46 UTC
First added · source update from Europe PMC

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