Novel Pan-ERR Agonists Ameliorate Heart Failure Through Enhancing Cardiac Fatty Acid Metabolism and Mitochondrial Function.

Xu W, Billon C, Li H, Wilderman A, Qi L, Graves A, Rideb JRDC, Zhao Y, Hayes M, Yu K, Losby M, Hampton CS and 15 more

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Adeyemi CM, Hong SJ, Nasiotis E, Fu C, Oh TG, Fan W, Downes M, Welch RD, Evans RM, Milosavljevic A, Walker JK, Jensen BC, Pei L, Burris T, Zhang L

Circulation14 Nov 2023Cited by 58 (Europe PMC)

PMID37961903PMCIDPMC10842599DOI10.1161/circulationaha.123.066542PepBankPUB-37961903

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Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study14

4 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
In pressure overload-induced heart failure, SLU‑PP‑332 significantly improved ejection fraction.
In plain wordsIn mice with pressure overload-induced heart failure, SLU‑PP‑332 improved ejection fraction.
Peptide
SLU-PP-332
Outcome
IncreaseEjection fraction
Study
mousen: not reported in source
Pressure overload-induced heart failure
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
Both SLU-PP-332 and SLU-PP-915 significantly improved ejection fraction, ameliorated fibrosis, and increased survival associated with pressure overload-induced HF without affecting cardiac hypertrophy.
2 context sentences(design, population, supporting numbers)
Summary · context
Using a structure-based design approach, we designed and synthesized 2 structurally distinct pan-ERR agonists, SLU-PP-332 and SLU-PP-915.
Summary · context
We investigated the effect of ERR agonist on cardiac function in a pressure overload-induced HF model in vivo.
Report a problemFND-3796190301
02AnimalAnimal study (in vivo)Efficacy outcome
In pressure overload-induced heart failure, SLU‑PP‑332 ameliorated fibrosis.
In plain wordsIn mice with pressure overload-induced heart failure, SLU‑PP‑332 reduced fibrosis.
Peptide
SLU-PP-332
Outcome
DecreaseCardiac fibrosis
Study
mousen: not reported in source
Pressure overload-induced heart failure
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
Both SLU-PP-332 and SLU-PP-915 significantly improved ejection fraction, ameliorated fibrosis, and increased survival associated with pressure overload-induced HF without affecting cardiac hypertrophy.
2 context sentences(design, population, supporting numbers)
Summary · context
Using a structure-based design approach, we designed and synthesized 2 structurally distinct pan-ERR agonists, SLU-PP-332 and SLU-PP-915.
Summary · context
We investigated the effect of ERR agonist on cardiac function in a pressure overload-induced HF model in vivo.
Report a problemFND-3796190302
03AnimalAnimal study (in vivo)Efficacy outcome
In pressure overload-induced heart failure, SLU‑PP‑332 increased survival.
In plain wordsIn mice with pressure overload-induced heart failure, SLU‑PP‑332 increased survival.
Peptide
SLU-PP-332
Outcome
IncreaseSurvival
Study
mousen: not reported in source
Pressure overload-induced heart failure
Outcome group
Mortality · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
Both SLU-PP-332 and SLU-PP-915 significantly improved ejection fraction, ameliorated fibrosis, and increased survival associated with pressure overload-induced HF without affecting cardiac hypertrophy.
2 context sentences(design, population, supporting numbers)
Summary · context
Using a structure-based design approach, we designed and synthesized 2 structurally distinct pan-ERR agonists, SLU-PP-332 and SLU-PP-915.
Summary · context
We investigated the effect of ERR agonist on cardiac function in a pressure overload-induced HF model in vivo.
Report a problemFND-3796190303
04AnimalAnimal study (in vivo)Efficacy outcome
In pressure overload-induced heart failure, SLU‑PP‑332 did not affect cardiac hypertrophy.
In plain wordsIn mice with pressure overload-induced heart failure, SLU‑PP‑332 did not affect cardiac hypertrophy.
Peptide
SLU-PP-332
Outcome
No significant changeCardiac hypertrophy
Study
mousen: not reported in source
Pressure overload-induced heart failure
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
Both SLU-PP-332 and SLU-PP-915 significantly improved ejection fraction, ameliorated fibrosis, and increased survival associated with pressure overload-induced HF without affecting cardiac hypertrophy.
2 context sentences(design, population, supporting numbers)
Summary · context
Using a structure-based design approach, we designed and synthesized 2 structurally distinct pan-ERR agonists, SLU-PP-332 and SLU-PP-915.
Summary · context
We investigated the effect of ERR agonist on cardiac function in a pressure overload-induced HF model in vivo.
Report a problemFND-3796190304

Studies that did not test the peptide alone10

In this study, SLU-PP-332 was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking SLU-PP-332.

05AnimalNot a test of SLU-PP-332 aloneAnimal study (in vivo)Mechanism
In mouse hearts with 6-week pressure overload, ERR agonists substantially normalized fatty acid and lipid metabolite profiles.
In plain wordsIn mice with 6-week pressure overload, ERR agonists, including SLU‑PP‑332, normalized heart fatty acid and lipid metabolite profiles.
Peptide
SLU-PP-332
Outcome
MixedFatty acid and lipid metabolite profiles
Study
mousen: not reported in source
Mouse hearts with 6-week pressure overload
Outcome group
Lipids · Cardiovascular
Source sentences
Summary
Metabolomics analysis showed substantial normalization of metabolic profiles in fatty acid/lipid and tricarboxylic acid/oxidative phosphorylation metabolites in the mouse heart with 6-week pressure overload.
2 context sentences(design, population, supporting numbers)
Summary · context
Using a structure-based design approach, we designed and synthesized 2 structurally distinct pan-ERR agonists, SLU-PP-332 and SLU-PP-915.
Summary · context
We investigated the effect of ERR agonist on cardiac function in a pressure overload-induced HF model in vivo.
In this study, SLU-PP-332 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking SLU-PP-332.
Report a problemFND-3796190306
06AnimalNot a test of SLU-PP-332 aloneAnimal study (in vivo)Mechanism
In mouse hearts with 6-week pressure overload, ERR agonists normalized tricarboxylic acid and oxidative phosphorylation metabolite profiles.
In plain wordsIn mice with 6-week pressure overload, ERR agonists, including SLU‑PP‑332, normalized heart tricarboxylic acid and oxidative phosphorylation metabolite profiles.
Peptide
SLU-PP-332
Outcome
MixedTricarboxylic acid and oxidative phosphorylation metabolite profiles
Study
mousen: not reported in source
Mouse hearts with 6-week pressure overload
Outcome group
Mitochondrial function · Cardiovascular
Source sentences
Summary
Metabolomics analysis showed substantial normalization of metabolic profiles in fatty acid/lipid and tricarboxylic acid/oxidative phosphorylation metabolites in the mouse heart with 6-week pressure overload.
2 context sentences(design, population, supporting numbers)
Summary · context
Using a structure-based design approach, we designed and synthesized 2 structurally distinct pan-ERR agonists, SLU-PP-332 and SLU-PP-915.
Summary · context
We investigated the effect of ERR agonist on cardiac function in a pressure overload-induced HF model in vivo.
In this study, SLU-PP-332 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking SLU-PP-332.
Report a problemFND-3796190307
07AnimalNot a test of SLU-PP-332 aloneAnimal study (in vivo)Mechanism
In vivo, ERR agonists increased mitochondrial oxidative capacity.
In plain wordsIn animal experiments, ERR agonists, including SLU‑PP‑332, increased mitochondrial oxidative capacity.
Peptide
SLU-PP-332
Outcome
IncreaseMitochondrial oxidative capacity in vivo
Study
mousen: not reported in source
Pressure overload-induced heart failure
Outcome group
Mitochondrial function · Cardiovascular
Source sentences
Summary
ERR agonists increase mitochondria oxidative capacity and fatty acid use in vitro and in vivo.
2 context sentences(design, population, supporting numbers)
Summary · context
Using a structure-based design approach, we designed and synthesized 2 structurally distinct pan-ERR agonists, SLU-PP-332 and SLU-PP-915.
Summary · context
We investigated the effect of ERR agonist on cardiac function in a pressure overload-induced HF model in vivo.
In this study, SLU-PP-332 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking SLU-PP-332.
Report a problemFND-3796190308
08AnimalNot a test of SLU-PP-332 aloneAnimal study (in vivo)Mechanism
In vivo, ERR agonists increased fatty acid use.
In plain wordsIn animal experiments, ERR agonists, including SLU‑PP‑332, increased fatty acid use.
Peptide
SLU-PP-332
Outcome
IncreaseFatty acid use in vivo
Study
mousen: not reported in source
Pressure overload-induced heart failure
Outcome group
Lipids · Cardiovascular
Source sentences
Summary
ERR agonists increase mitochondria oxidative capacity and fatty acid use in vitro and in vivo.
2 context sentences(design, population, supporting numbers)
Summary · context
Using a structure-based design approach, we designed and synthesized 2 structurally distinct pan-ERR agonists, SLU-PP-332 and SLU-PP-915.
Summary · context
We investigated the effect of ERR agonist on cardiac function in a pressure overload-induced HF model in vivo.
In this study, SLU-PP-332 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking SLU-PP-332.
Report a problemFND-3796190309
09AnimalNot a test of SLU-PP-332 aloneOther designMechanism
In heart failure experiments, ERR agonists transcriptionally activated a broad spectrum of metabolic genes.
In plain wordsIn heart failure models, ERR agonists, including SLU‑PP‑332, activated metabolic genes, particularly those related to fatty acids and mitochondria.
Peptide
SLU-PP-332
Outcome
IncreaseMetabolic gene transcription
Study
n: not reported in source
In vivo and in vitro heart failure experiments
Outcome group
Receptor activity and mechanism · Cardiovascular
Source sentences
Summary
A broad spectrum of metabolic genes was transcriptionally activated by ERR agonists, particularly genes involved in fatty acid metabolism and mitochondrial function.
2 context sentences(design, population, supporting numbers)
Summary · context
Using a structure-based design approach, we designed and synthesized 2 structurally distinct pan-ERR agonists, SLU-PP-332 and SLU-PP-915.
Summary · context
We investigated the effect of ERR agonist on cardiac function in a pressure overload-induced HF model in vivo.
In this study, SLU-PP-332 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking SLU-PP-332.
Report a problemFND-3796190305
10AnimalNot a test of SLU-PP-332 aloneOther designMechanism
In genetic dependency experiments, ERRγ primarily mediated ERR agonism-induced transcriptional regulation and cardioprotection, supporting target specificity.
In plain wordsIn genetic dependency experiments, ERRγ mainly mediated transcriptional regulation and heart protection from ERR agonists, including SLU‑PP‑332.
Peptide
SLU-PP-332
Outcome
Not applicableERRγ mediation and target specificity
Study
n: not reported in source
In vivo and in vitro genetic dependency experiments
Outcome group
Receptor activity and mechanism · Cardiovascular
Source sentences
Summary
Using both in vitro and in vivo genetic dependency experiments, we show that ERRγ is the main mediator of ERR agonism-induced transcriptional regulation and cardioprotection and definitively demonstrated target specificity.
2 context sentences(design, population, supporting numbers)
Summary · context
Using a structure-based design approach, we designed and synthesized 2 structurally distinct pan-ERR agonists, SLU-PP-332 and SLU-PP-915.
Summary · context
We investigated the effect of ERR agonist on cardiac function in a pressure overload-induced HF model in vivo.
In this study, SLU-PP-332 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking SLU-PP-332.
Report a problemFND-3796190312
11LabNot a test of SLU-PP-332 aloneIn vitro (cells)Mechanism
In vitro, ERR agonists increased mitochondrial oxidative capacity.
In plain wordsIn cells, ERR agonists, including SLU‑PP‑332, increased mitochondrial oxidative capacity.
Peptide
SLU-PP-332
Outcome
IncreaseMitochondrial oxidative capacity in vitro
Study
n: not reported in source
Outcome group
Mitochondrial function · Cardiovascular
Source sentences
Summary
ERR agonists increase mitochondria oxidative capacity and fatty acid use in vitro and in vivo.
2 context sentences(design, population, supporting numbers)
Summary · context
Using a structure-based design approach, we designed and synthesized 2 structurally distinct pan-ERR agonists, SLU-PP-332 and SLU-PP-915.
Summary · context
We investigated the effect of ERR agonist on cardiac function in a pressure overload-induced HF model in vivo.
In this study, SLU-PP-332 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking SLU-PP-332.
Report a problemFND-3796190310
12LabNot a test of SLU-PP-332 aloneIn vitro (cells)Mechanism
In vitro, ERR agonists increased fatty acid use.
In plain wordsIn cells, ERR agonists, including SLU‑PP‑332, increased fatty acid use.
Peptide
SLU-PP-332
Outcome
IncreaseFatty acid use in vitro
Study
n: not reported in source
Outcome group
Lipids · Cardiovascular
Source sentences
Summary
ERR agonists increase mitochondria oxidative capacity and fatty acid use in vitro and in vivo.
2 context sentences(design, population, supporting numbers)
Summary · context
Using a structure-based design approach, we designed and synthesized 2 structurally distinct pan-ERR agonists, SLU-PP-332 and SLU-PP-915.
Summary · context
We investigated the effect of ERR agonist on cardiac function in a pressure overload-induced HF model in vivo.
In this study, SLU-PP-332 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking SLU-PP-332.
Report a problemFND-3796190311
13LabNot a test of SLU-PP-332 aloneIn vitro (cells)Mechanism
In cardiomyocytes, ERR agonism downregulated cell cycle pathways, partly through E2F1.
In plain wordsIn cells, ERR agonism, including SLU‑PP‑332 experiments, reduced cell cycle pathway activity, partly through E2F1.
Peptide
SLU-PP-332
Outcome
DecreaseCell cycle pathway regulation
Study
n: not reported in source
Cardiomyocytes
Outcome group
Receptor activity and mechanism · Cardiovascular
Source sentences
Summary
ERR agonism also led to downregulation of cell cycle and development pathways, which was partially mediated by E2F1 in cardiomyocytes.
2 context sentences(design, population, supporting numbers)
Summary · context
Using a structure-based design approach, we designed and synthesized 2 structurally distinct pan-ERR agonists, SLU-PP-332 and SLU-PP-915.
Summary · context
We investigated the effect of ERR agonist on cardiac function in a pressure overload-induced HF model in vivo.
In this study, SLU-PP-332 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking SLU-PP-332.
Report a problemFND-3796190313
14LabNot a test of SLU-PP-332 aloneIn vitro (cells)Mechanism
In cardiomyocytes, ERR agonism downregulated development pathways, partly through E2F1.
In plain wordsIn cells, ERR agonism, including SLU‑PP‑332 experiments, reduced development pathway activity, partly through E2F1.
Peptide
SLU-PP-332
Outcome
DecreaseDevelopment pathway regulation
Study
n: not reported in source
Cardiomyocytes
Outcome group
Receptor activity and mechanism · Cardiovascular
Source sentences
Summary
ERR agonism also led to downregulation of cell cycle and development pathways, which was partially mediated by E2F1 in cardiomyocytes.
2 context sentences(design, population, supporting numbers)
Summary · context
Using a structure-based design approach, we designed and synthesized 2 structurally distinct pan-ERR agonists, SLU-PP-332 and SLU-PP-915.
Summary · context
We investigated the effect of ERR agonist on cardiac function in a pressure overload-induced HF model in vivo.
In this study, SLU-PP-332 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking SLU-PP-332.
Report a problemFND-3796190314

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

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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