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Study · Animal study (in vivo) · mouse · 2014

3 results

Novel exenatide analogs with peptidic albumin binding domains: potent anti-diabetic agents with extended duration of action.

Levy OE, Jodka CM, Ren SS, Mamedova L, Sharma A, Samant M, D'Souza LJ, Soares CJ, Yuskin DR, Jin LJ, Parkes DG, Tatarkiewicz K, Ghosh SS

PloS one4 Feb 2014Cited by 36 (Europe PMC)

PMID24503632 (opens in a new tab)PMCIDPMC3913652 (opens in a new tab)DOI10.1371/journal.pone.0087704 (opens in a new tab)PepBankPUB-24503632
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Summary

The design, synthesis and pharmacology of novel long-acting exenatide analogs for the treatment of metabolic diseases are described. These molecules display enhanced pharmacokinetic profile and potent glucoregulatory and weight lowering actions compared to native exenatide. [Leu(14)]exenatide-ABD is an 88 residue peptide amide incorporating an Albumin Binding Domain (ABD) scaffold. [Leu(14)]exenatide-ABP is a 53 residue peptide incorporating a short Albumin Binding Peptide (ABP). [Leu(14)]exenatide-ABD and [Leu(14)]exenatide-ABP exhibited nanomolar functional GLP-1 receptor potency and were metabolically stable in vitro in human plasma and in a pancreatic digestive enzyme mixture. Both molecules displayed picomolar and nanomolar binding association with albumin across multiple species and circulating half lives of 16 and 11 hours, respectively, post a single IV dose in rats. Unlike exenatide, both molecules elicited robust glucose lowering when injected 1 day prior to an oral glucose tolerance test, indicative of their extended duration of action. [Leu(14)]exenatide-ABD was compared to exenatide in a Lep (ob/ob) mouse model of diabetes. Twice-weekly subcutaneously dosed [Leu(14)]exenatide-ABD displayed superior glucose lowering and weight loss in diabetic mice when compared to continuously infused exenatide at the same total weekly dose. A single oral administration of each molecule via an enteric coated capsule to cynomolgus monkeys showed superior pharmacokinetics for [Leu(14)]exenatide-ABD as compared to [Leu(14)]exenatide-ABP with detectable exposure longer than 14 days. These studies support the potential use of these novel long acting exenatide analogs with different routes of administration for the treatment of type 2 diabetes.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

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

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    Native exenatide did not elicit robust glucose lowering when injected 1 day before an oral glucose tolerance test, unlike both analogs.

    In plain wordsIn animals, native exenatide did not produce the robust delayed glucose reduction seen with the analogs.

    Peptide
    Exenatide (exendin-4)
    Outcome
    DecreaseDelayed glucose lowering
    Study

    n: not reported in source

    Comparator
    [Leu(14)]exenatide-ABD and [Leu(14)]exenatide-ABP
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Unlike exenatide, both molecules elicited robust glucose lowering when injected 1 day prior to an oral glucose tolerance test, indicative of their extended duration of action.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In diabetic mice, continuously infused exenatide lowered glucose less than twice-weekly [Leu(14)]exenatide-ABD at the same weekly dose.

    In plain wordsIn mice with diabetes, infused exenatide lowered glucose less than the albumin-binding analog at the same weekly dose.

    Peptide
    Exenatide (exendin-4)
    Outcome
    DecreaseGlucose lowering
    Study

    mousen: not reported in source

    Lep (ob/ob) diabetic mice
    Comparator
    [Leu(14)]exenatide-ABD
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Twice-weekly subcutaneously dosed [Leu(14)]exenatide-ABD displayed superior glucose lowering and weight loss in diabetic mice when compared to continuously infused exenatide at the same total weekly dose.
    1 context sentence
    Summary · context
    [Leu(14)]exenatide-ABD was compared to exenatide in a Lep (ob/ob) mouse model of diabetes.
  3. 03AnimalAnimal study (in vivo)Efficacy outcome

    In diabetic mice, continuously infused exenatide produced less weight loss than twice-weekly [Leu(14)]exenatide-ABD at the same weekly dose.

    In plain wordsIn mice with diabetes, infused exenatide produced less weight loss than the albumin-binding analog at the same weekly dose.

    Peptide
    Exenatide (exendin-4)
    Outcome
    DecreaseWeight loss
    Study

    mousen: not reported in source

    Lep (ob/ob) diabetic mice
    Comparator
    [Leu(14)]exenatide-ABD
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Twice-weekly subcutaneously dosed [Leu(14)]exenatide-ABD displayed superior glucose lowering and weight loss in diabetic mice when compared to continuously infused exenatide at the same total weekly dose.
    1 context sentence
    Summary · context
    [Leu(14)]exenatide-ABD was compared to exenatide in a Lep (ob/ob) mouse model of diabetes.

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.

  1. Version 2Current

    22 Oct 2026, 02:26 UTC

    Study results updated

  2. Version 1

    21 Oct 2026, 18:59 UTC

    First added · source update from Europe PMC

Subjects

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