| Autor: |
Floriane Lignet, Christina Esdar, Gina Walter-Bausch, Manja Friese-Hamim, Sofia Stinchi, Elise Drouin, Samer El Bawab, Andreas D. Becker, Claude Gimmi, Michael P. Sanderson, Felix Rohdich |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
The Journal of pharmacology and experimental therapeutics. |
| ISSN: |
1521-0103 |
| Popis: |
M3258 is an orally bioavailable, potent, selective, reversible inhibitor of the large multifunctional peptidase 7 (LMP7, β5i, PSMB8) proteolytic subunit of the immunoproteasome; a component of the cellular protein degradation machinery, highly expressed in malignant hematopoietic cells including multiple myeloma. Here we describe the fit-for-purpose PK/PD/efficacy modelling of M3258 based on preclinical data from several species. The inhibition of LMP7 activity (PD) and tumor growth (efficacy) were tested in human multiple myeloma xenografts in mice. PK and efficacy data were correlated yielding a free M3258 concentration of 45 nM for half-maximal tumor growth inhibition (KC |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
