Strategic Approaches to Optimizing Peptide ADME Properties
Open accessAbstract
Development of peptide drugs is challenging but also quite rewarding. Five blockbuster peptide drugs are currently on the market, and six new peptides received first marketing approval as new molecular entities in 2012. Although peptides only represent 2% of the drug market, the market is growing twice as quickly and might soon occupy a larger niche. Natural peptides typically have poor absorption, distribution, metabolism, and excretion (ADME) properties with rapid clearance, short half-life, low permeability, and sometimes low solubility. Strategies have been developed to improve peptide drugability through enhancing permeability, reducing proteolysis and renal clearance, and prolonging half-life. In vivo, in vitro, and in silico tools are available to evaluate ADME properties of peptides, and structural modification strategies are in place to improve peptide developability.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Activation of Apoptosis in Vivo by a Hydrocarbon-Stapled BH3 Helix
Walensky, L. D., Kung, A. L., Escher, I., Malia, T. J., Barbuto, S., Wright, R. D., Wagner, G., Verdine, G. L., & Korsmeyer, S. J. (2004) · Science · doi:10.1126/science.1099191 · Cited by 1,349 · see citing works
Delivery of Therapeutic Proteins
Pisal, D. S., Kosloski, M. P., & Balu-Iyer, S. V. (2010) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.22054 · Cited by 532 · see citing works
Pratley, R. E., Nauck, M. A., Barnett, A. H., Feinglos, M. N., Ovalle, F., Harman-Boehm, I., Ye, J., Scott, R., Johnson, S., Stewart, M., et al. (2014) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(13)70214-6 · Cited by 326 · see citing works
Peptides As Therapeutics with Enhanced Bioactivity
Goodwin, D., Simerska, P., & Toth, I. (2012) · Current Medicinal Chemistry · doi:10.2174/092986712803251548 · Cited by 176 · see citing works
Albiglutide: First Global Approval
Poole, R. M., & Nowlan, M. L. (2014) · Drugs · doi:10.1007/s40265-014-0228-2 · Cited by 49 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Therapeutic Peptides: Current Applications and Future Directions
Wang, L., Wang, N., Zhang, W., Cheng, X., Yan, Z., Shao, G., Wang, X., Wang, R., & Fu, C. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00904-4 · Cited by 2,131 · see citing works
Therapeutic peptides: Historical perspectives, current development trends, and future directions
Lau, J. L., & Dunn, M. K. (2018) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2017.06.052 · Cited by 1,879 · see citing works
The evolution of commercial drug delivery technologies
Vargason, A. M., Anselmo, A. C., & Mitragotri, S. (2021) · Nature Biomedical Engineering · doi:10.1038/s41551-021-00698-w · Cited by 1,361 · see citing works
Zinsli, L. V., Stierlin, N., Loessner, M. J., & Schmelcher, M. (2021) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2020.12.024 · Cited by 63 · see citing works
Knerr, P. J., Mowery, S. A., Finan, B., Perez-Tilve, D., Tschöp, M. H., & DiMarchi, R. D. (2020) · Peptides · doi:10.1016/j.peptides.2019.170225 · Cited by 49 · see citing works
Application of Novel Degraders Employing Autophagy for Expediting Medicinal Research
Li, X., Liu, Q., Xie, X., Peng, C., Pang, Q., Liu, B., & Han, B. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c01712 · Cited by 46 · see citing works
Metrangolo, V., Ploug, M., & Engelholm, L. H. (2021) · Cancers · doi:10.3390/cancers13215376 · Cited by 44 · see citing works
- Authors
- Di, L.
- Affiliations
- Pfizer (United States) (US)
- Corresponding author
- Di, Li
- ORCID
- Di, Li
- Venue
- The AAPS Journal
- Published
- 2014-11-04
- Volume
- 17
- Issue
- 1
- Pages
- 134-143
- ISSN
- 1550-7416 (ISSN-L)
- PMC
- PMC4287298
- OpenAlex
- W2068275014
- Cited by
- 669
- References
- 5
- Citations by year
- 2026: 64 · 2025: 65 · 2024: 76 · 2023: 65 · 2022: 83 · 2021: 87 · 2020: 69 · 2019: 51 · 2018: 49 · 2017: 40 · 2016: 14 · 2015: 5
- FWCI
- 1.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- The AAPS Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
- Keywords
- peptide therapeutics, ADME properties, drug developability, peptide permeability, proteolysis, renal clearance, half-life extension, structural modification, peptide solubility
- MeSH terms
- Animals, Computer Simulation, Half-Life, Humans, Peptides, Permeability, Solubility, Drug Design, Drug Approval
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
