Pharmacokinetic Analysis of Omomyc Shows Lasting Structural Integrity and Long Terminal Half-Life in Tumor Tissue
MYC is an oncoprotein causally involved in the majority of human cancers and a most wanted target for cancer treatment. Omomyc is the best-characterized MYC dominant negative to date. In the last years, it has been developed into a therapeutic miniprotein for solid tumor treatment and recently reach...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/3/826 |
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| author | Marie-Eve Beaulieu Sandra Martínez-Martín Jastrinjan Kaur Virginia Castillo Cano Daniel Massó-Vallés Laia Foradada Felip Sergio López-Estévez Erika Serrano del Pozo Hugo Thabussot Laura Soucek |
| author_facet | Marie-Eve Beaulieu Sandra Martínez-Martín Jastrinjan Kaur Virginia Castillo Cano Daniel Massó-Vallés Laia Foradada Felip Sergio López-Estévez Erika Serrano del Pozo Hugo Thabussot Laura Soucek |
| author_sort | Marie-Eve Beaulieu |
| collection | DOAJ |
| description | MYC is an oncoprotein causally involved in the majority of human cancers and a most wanted target for cancer treatment. Omomyc is the best-characterized MYC dominant negative to date. In the last years, it has been developed into a therapeutic miniprotein for solid tumor treatment and recently reached clinical stage. However, since the in vivo stability of therapeutic proteins, especially within the tumor vicinity, can be affected by proteolytic degradation, the perception of Omomyc as a valid therapeutic agent has been often questioned. In this study, we used a mass spectrometry approach to evaluate the stability of Omomyc in tumor biopsies from murine xenografts following its intravenous administration. Our data strongly support that the integrity of the functional domains of Omomyc (DNA binding and dimerization region) remains preserved in the tumor tissue for at least 72 hours following administration and that the protein shows superior pharmacokinetics in the tumor compartment compared with blood serum. |
| first_indexed | 2024-03-11T09:50:26Z |
| format | Article |
| id | doaj.art-c652344981924fa6814bc0f0ccdbb43a |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T09:50:26Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-c652344981924fa6814bc0f0ccdbb43a2023-11-16T16:17:46ZengMDPI AGCancers2072-66942023-01-0115382610.3390/cancers15030826Pharmacokinetic Analysis of Omomyc Shows Lasting Structural Integrity and Long Terminal Half-Life in Tumor TissueMarie-Eve Beaulieu0Sandra Martínez-Martín1Jastrinjan Kaur2Virginia Castillo Cano3Daniel Massó-Vallés4Laia Foradada Felip5Sergio López-Estévez6Erika Serrano del Pozo7Hugo Thabussot8Laura Soucek9Peptomyc S.L., Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, SpainPeptomyc S.L., Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, SpainPreclinical & Translational Research Program, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, SpainPeptomyc S.L., Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, SpainPeptomyc S.L., Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, SpainPeptomyc S.L., Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, SpainPeptomyc S.L., Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, SpainPreclinical & Translational Research Program, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, SpainPeptomyc S.L., Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, SpainPeptomyc S.L., Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, SpainMYC is an oncoprotein causally involved in the majority of human cancers and a most wanted target for cancer treatment. Omomyc is the best-characterized MYC dominant negative to date. In the last years, it has been developed into a therapeutic miniprotein for solid tumor treatment and recently reached clinical stage. However, since the in vivo stability of therapeutic proteins, especially within the tumor vicinity, can be affected by proteolytic degradation, the perception of Omomyc as a valid therapeutic agent has been often questioned. In this study, we used a mass spectrometry approach to evaluate the stability of Omomyc in tumor biopsies from murine xenografts following its intravenous administration. Our data strongly support that the integrity of the functional domains of Omomyc (DNA binding and dimerization region) remains preserved in the tumor tissue for at least 72 hours following administration and that the protein shows superior pharmacokinetics in the tumor compartment compared with blood serum.https://www.mdpi.com/2072-6694/15/3/826protein therapeuticsMYCOmomycmass spectrometryLC-PRM |
| spellingShingle | Marie-Eve Beaulieu Sandra Martínez-Martín Jastrinjan Kaur Virginia Castillo Cano Daniel Massó-Vallés Laia Foradada Felip Sergio López-Estévez Erika Serrano del Pozo Hugo Thabussot Laura Soucek Pharmacokinetic Analysis of Omomyc Shows Lasting Structural Integrity and Long Terminal Half-Life in Tumor Tissue Cancers protein therapeutics MYC Omomyc mass spectrometry LC-PRM |
| title | Pharmacokinetic Analysis of Omomyc Shows Lasting Structural Integrity and Long Terminal Half-Life in Tumor Tissue |
| title_full | Pharmacokinetic Analysis of Omomyc Shows Lasting Structural Integrity and Long Terminal Half-Life in Tumor Tissue |
| title_fullStr | Pharmacokinetic Analysis of Omomyc Shows Lasting Structural Integrity and Long Terminal Half-Life in Tumor Tissue |
| title_full_unstemmed | Pharmacokinetic Analysis of Omomyc Shows Lasting Structural Integrity and Long Terminal Half-Life in Tumor Tissue |
| title_short | Pharmacokinetic Analysis of Omomyc Shows Lasting Structural Integrity and Long Terminal Half-Life in Tumor Tissue |
| title_sort | pharmacokinetic analysis of omomyc shows lasting structural integrity and long terminal half life in tumor tissue |
| topic | protein therapeutics MYC Omomyc mass spectrometry LC-PRM |
| url | https://www.mdpi.com/2072-6694/15/3/826 |
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