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Peer-reviewedCC BYCancers

From Infection to Oncology: AI-Assisted Drug Repurposing Uncovers Anti-Infective and Excipient-Class Compounds as PPAR-α-Linked Anticancer Agents

  • Shoeb Ikhlas1,2,3
  • Amani Alsharidah4
  • Reem A. Alkhodier1,3,5
  • Sergio Senar6
  • Mohamed Boudjelal1,2,3
6 affiliations
  1. 1King Abdullah International Medical Research Center (KAIMRC), Riyadh 11481, Saudi Arabia
  2. 2King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia
  3. 3Ministry of National Guard Health Affairs (MNGHA), Riyadh 11481, Saudi Arabia
  4. 4College of Science, King Saud University, Riyadh 11459, Saudi Arabia
  5. 5Department of Pharmaceutical Sciences, College of Pharmacy, King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia
  6. 6Machine Learning Applied to Drug Discovery, DrTarget, C/Alejo Carpentier 13, 28806 Alcalá De Henares, Spain
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Abstract

Drug repurposing offers an efficient strategy to identify novel anticancer agents from marketed compounds. We screened a library of ~1400 approved drugs using a PPARE–PPAR-α luciferase reporter assay to uncover modulators of lipid metabolism that induce cancer cell death without direct binding to PPARα. This primary screen identified 224 compounds inhibiting reporter activity by >50%, of which 26 demonstrated ≥50% cytotoxicity in KAIMRC1 breast cancer and HCT116 colorectal cancer cells at 10 µM after 48 h incubation. AI-based DrTarget analysis classified these hits, with Group 1 comprising four previously unrecognized anticancer agents: antibiotics cefditoren pivoxil, tebipenem pivoxil, broxyquinoline, and cosmetic ingredient 1-hexadecanol. Dose–response studies across KAIMRC1, HCT116, and SW480 cells revealed IC50 values as low as ~10 µM, comparable to daunorubicin, a well-known anti-cancer drug. Apoptosis profiling confirmed activation of intrinsic/extrinsic pathways via cytochrome c, SMAC/Diablo, TRAIL-R1/DR4, and phospho-p53 modulation. Based on these findings, we propose the repurposing of Broxyquinoline, 1-Hexadecanol, Cefditoren Pivoxil, and Tebipenem Pivoxil as potential anti-cancer drugs.

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Cite

BibTeXRIS
BibTeX
@article{ikhlas2026from,
  title = {{From Infection to Oncology: AI-Assisted Drug Repurposing Uncovers Anti-Infective and Excipient-Class Compounds as PPAR-α-Linked Anticancer Agents}},
  author = {Shoeb Ikhlas and Amani Alsharidah and Reem A. Alkhodier and Sergio Senar and Mohamed Boudjelal},
  journal = {Cancers},
  year = {2026},
  month = oct,
  doi = {10.3390/cancers18193231},
  url = {https://europepmc.org/article/PMC/PMC13664190},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - From Infection to Oncology: AI-Assisted Drug Repurposing Uncovers Anti-Infective and Excipient-Class Compounds as PPAR-α-Linked Anticancer Agents
AU  - Shoeb Ikhlas
AU  - Amani Alsharidah
AU  - Reem A. Alkhodier
AU  - Sergio Senar
AU  - Mohamed Boudjelal
PY  - 2026
DA  - 2026/10/01
JO  - Cancers
DO  - 10.3390/cancers18193231
UR  - https://europepmc.org/article/PMC/PMC13664190
AB  - Drug repurposing offers an efficient strategy to identify novel anticancer agents from marketed compounds. We screened a library of ~1400 approved drugs using a PPARE–PPAR-α luciferase reporter assay to uncover modulators of lipid metabolism that induce cancer cell death without direct binding to PPARα. This primary screen identified 224 compounds inhibiting reporter activity by >50%, of which 26 demonstrated ≥50% cytotoxicity in KAIMRC1 breast cancer and HCT116 colorectal cancer cells at 10 µM after 48 h incubation. AI-based DrTarget analysis classified these hits, with Group 1 comprising four previously unrecognized anticancer agents: antibiotics cefditoren pivoxil, tebipenem pivoxil, broxyquinoline, and cosmetic ingredient 1-hexadecanol. Dose–response studies across KAIMRC1, HCT116, and SW480 cells revealed IC50 values as low as ~10 µM, comparable to daunorubicin, a well-known anti-cancer drug. Apoptosis profiling confirmed activation of intrinsic/extrinsic pathways via cytochrome c, SMAC/Diablo, TRAIL-R1/DR4, and phospho-p53 modulation. Based on these findings, we propose the repurposing of Broxyquinoline, 1-Hexadecanol, Cefditoren Pivoxil, and Tebipenem Pivoxil as potential anti-cancer drugs.
SN  - 2072-6694
ER  -