PUBLICATION
Photocaging of N-pyridinyl amide scaffold-based PIM inhibitors for spatiotemporal controlled anticancer bioactivity
- Authors
- Lu, M., Liu, H., Xiang, R., Li, J., Wu, T., Deng, M., Jia, Y., Liu, X., Yang, Y., Ge, Y., Cai, T., Wu, J., Ling, Y., Zhou, Y.
- ID
- ZDB-PUB-250406-6
- Date
- 2025
- Source
- Bioorganic & Medicinal Chemistry 124: 118159118159 (Journal)
- Registered Authors
- Keywords
- N-pyridinyl amide derivatives, PIM inhibitors, Photocage, Prostate cancer, Spatiotemporal control
- MeSH Terms
-
- Amides*/chemical synthesis
- Amides*/chemistry
- Amides*/pharmacology
- Animals
- Antineoplastic Agents*/chemical synthesis
- Antineoplastic Agents*/chemistry
- Antineoplastic Agents*/pharmacology
- Apoptosis/drug effects
- Cell Line, Tumor
- Cell Proliferation/drug effects
- Dose-Response Relationship, Drug
- Drug Screening Assays, Antitumor
- Humans
- Light
- Molecular Structure
- Neoplasms, Experimental/drug therapy
- Neoplasms, Experimental/pathology
- Protein Kinase Inhibitors*/chemical synthesis
- Protein Kinase Inhibitors*/chemistry
- Protein Kinase Inhibitors*/pharmacology
- Proto-Oncogene Proteins c-pim-1*/antagonists & inhibitors
- Proto-Oncogene Proteins c-pim-1*/metabolism
- Pyridines*/chemical synthesis
- Pyridines*/chemistry
- Pyridines*/pharmacology
- Structure-Activity Relationship
- Zebrafish
- PubMed
- 40186922 Full text @ Bioorg. Med. Chem.
Citation
Lu, M., Liu, H., Xiang, R., Li, J., Wu, T., Deng, M., Jia, Y., Liu, X., Yang, Y., Ge, Y., Cai, T., Wu, J., Ling, Y., Zhou, Y. (2025) Photocaging of N-pyridinyl amide scaffold-based PIM inhibitors for spatiotemporal controlled anticancer bioactivity. Bioorganic & Medicinal Chemistry. 124:118159118159.
Abstract
Photocaging is an ideal way to enable spatiotemporal control over the release of bioactive compounds for cancer treatments. In this work, a series of photocaged N-pyridinyl amide scaffold-based PIM inhibitors were developed by rendering the amino group unable to bind to the Asp128/Glu171 sites of PIM kinase with a photoremovable protecting group (PPG). Upon light irradiation, our studies revealed the structure-dependent photouncaging efficiency and screened out the photocaged PIM inhibitor FD1024-PPG. Its spatiotemporally controlled bioactivity was confirmed by cell-based in-vitro assays and revealed that it exerts the antiproliferation and induction of cell apoptosis through inhibition of PIM kinase upon light irradiation. Furthermore, the spatiotemporal control over the in-vivo anticancer activity was demonstrated using zebrafish xenograft model.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping