SD-2102, a Novel PDK1 Inhibitor, Suppresses Lung Cancer Growth by Targeting PDK1/Akt Signaling Pathway
4 affiliations
- 1Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon 21999 Seoul 06974 Republic of Korea
- 2College of Veterinary Medicine, Seoul National University, Seoul 08826 Seoul 06974 Republic of Korea
- 3College of Pharmacy, Gachon University, Incheon 21936 Seoul 06974 Republic of Korea
- 4College of Pharmacy, Chung-Ang University Seoul 06974 Republic of Korea
Abstract
The phosphoinositide-dependent kinase-1 (PDK1)-Akt signaling pathway plays a central role in regulating diverse cellular processes, including cell growth, survival, and metabolism. Dysregulation of this pathway is frequently observed in malignancies and is associated with tumor progression and resistance to therapy. Despite the recognized therapeutic potential of PDK1, potent and selective inhibitors remain limited. In this study, we developed and characterized a novel PDK1 inhibitor, SD-2102, and evaluated its anticancer effects in vitro and in vivo. A novel small-molecule compound, SD-2102, was synthesized and screened for PDK1 inhibitory activity. Binding affinity and interaction sites were examined using biochemical assays to identify the targeted domain. Functional assays, including cell proliferation, cell cycle analysis, and apoptosis detection, were performed in cancer cell lines. The in vivo efficacy of SD-2102 was assessed using a xenograft model. SD-2102 was predicted to interact with the pleckstrin homology domain of PDK1 and reduced PDK1 plasma membrane translocation. This inhibition led to decreased phosphorylation and activation of Akt. In vitro, SD-2102 suppressed cancer cell proliferation by inducing G1 phase arrest and promoting apoptosis. Importantly, SD-2102 induced minimal apoptosis in BEAS-2B non-tumorigenic human bronchial epithelial cells, supporting a preferential apoptotic effect toward lung cancer cells. In vivo, treatment with SD-2102 significantly reduced tumor growth in the xenograft model, consistent with the cellular findings. Together, these findings suggest that SD-2102 suppresses PDK1/Akt signaling while exhibiting preferential anticancer activity in lung cancer cells, supporting its further development as an anticancer agent.
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BibTeX
@article{namgung2026sd2102,
title = {{SD-2102, a Novel PDK1 Inhibitor, Suppresses Lung Cancer Growth by Targeting PDK1/Akt Signaling Pathway}},
author = {Hee Namgung and Se Yong Park and Om Darlami and Jung Ho Hwang and Ju-Hee Kang and Yoonji Lee and Dongyun Shin and Seung Hyun Oh},
journal = {Biomolecules \& Therapeutics},
year = {2026},
month = nov,
doi = {10.4062/biomolther.2026.131},
url = {https://doi.org/10.4062/biomolther.2026.131},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - SD-2102, a Novel PDK1 Inhibitor, Suppresses Lung Cancer Growth by Targeting PDK1/Akt Signaling Pathway
AU - Hee Namgung
AU - Se Yong Park
AU - Om Darlami
AU - Jung Ho Hwang
AU - Ju-Hee Kang
AU - Yoonji Lee
AU - Dongyun Shin
AU - Seung Hyun Oh
PY - 2026
DA - 2026/11/01
JO - Biomolecules & Therapeutics
DO - 10.4062/biomolther.2026.131
UR - https://doi.org/10.4062/biomolther.2026.131
AB - The phosphoinositide-dependent kinase-1 (PDK1)-Akt signaling pathway plays a central role in regulating diverse cellular processes, including cell growth, survival, and metabolism. Dysregulation of this pathway is frequently observed in malignancies and is associated with tumor progression and resistance to therapy. Despite the recognized therapeutic potential of PDK1, potent and selective inhibitors remain limited. In this study, we developed and characterized a novel PDK1 inhibitor, SD-2102, and evaluated its anticancer effects in vitro and in vivo. A novel small-molecule compound, SD-2102, was synthesized and screened for PDK1 inhibitory activity. Binding affinity and interaction sites were examined using biochemical assays to identify the targeted domain. Functional assays, including cell proliferation, cell cycle analysis, and apoptosis detection, were performed in cancer cell lines. The in vivo efficacy of SD-2102 was assessed using a xenograft model. SD-2102 was predicted to interact with the pleckstrin homology domain of PDK1 and reduced PDK1 plasma membrane translocation. This inhibition led to decreased phosphorylation and activation of Akt. In vitro, SD-2102 suppressed cancer cell proliferation by inducing G1 phase arrest and promoting apoptosis. Importantly, SD-2102 induced minimal apoptosis in BEAS-2B non-tumorigenic human bronchial epithelial cells, supporting a preferential apoptotic effect toward lung cancer cells. In vivo, treatment with SD-2102 significantly reduced tumor growth in the xenograft model, consistent with the cellular findings. Together, these findings suggest that SD-2102 suppresses PDK1/Akt signaling while exhibiting preferential anticancer activity in lung cancer cells, supporting its further development as an anticancer agent.
SN - 1976-9148
SN - 2005-4483
ER -