Quinoline-5,8-dione CDC25 inhibitors: Potent anti-cancer agents in leukemia and patient-derived colorectal organoids.
1/5 보강
Cell division cycle 25 (CDC25) phosphatases are critical activators of cyclin-dependent kinases (CDKs) and guardians of genome integrity, making them attractive anticancer targets.
APA
Narwanti I, Yu ZY, et al. (2026). Quinoline-5,8-dione CDC25 inhibitors: Potent anti-cancer agents in leukemia and patient-derived colorectal organoids.. European journal of medicinal chemistry, 301, 118215. https://doi.org/10.1016/j.ejmech.2025.118215
MLA
Narwanti I, et al.. "Quinoline-5,8-dione CDC25 inhibitors: Potent anti-cancer agents in leukemia and patient-derived colorectal organoids.." European journal of medicinal chemistry, vol. 301, 2026, pp. 118215.
PMID
41045697 ↗
Abstract 한글 요약
Cell division cycle 25 (CDC25) phosphatases are critical activators of cyclin-dependent kinases (CDKs) and guardians of genome integrity, making them attractive anticancer targets. Building on the quinoline-5,8-dione scaffold NSC663284 (6a), we synthesized derivatives with diverse C-6/C-7 alkylamino side chains. Structure-activity studies identified D3a/D3b (2-(4-methylpiperidin-1-yl)ethylamino) and D11a/D11b (2-(dimethylamino)ethylamino) as the most potent, exhibiting low-submicromolar inhibition of CDC25. In cell-based assays, these compounds suppressed leukemia (IC 0.21-1.22 μM) and colorectal cancer (IC 0.13-1.50 μM) viability, with reduced toxicity in normal colonic epithelial cells. Mechanistically, these derivatives blocked CDC25-mediated CDK1 Tyr15 dephosphorylation, delayed G/M progression, and induced caspase-dependent apoptosis with DNA damage. Cytotoxic potency correlated with baseline CDC25C expression, confirming on-target activity. Notably, efficacy was validated in colorectal cancer patient-derived organoids, providing clinically relevant insights into patient-specific responses. Together, these findings define a new class of CDC25 inhibitors with potent and selective anticancer activity, advancing prospects for next-generation therapeutics in leukemia and colorectal cancer.
🏷️ 키워드 / MeSH 📖 같은 키워드 OA만
- Humans
- cdc25 Phosphatases
- Antineoplastic Agents
- Colorectal Neoplasms
- Leukemia
- Structure-Activity Relationship
- Drug Screening Assays
- Antitumor
- Organoids
- Molecular Structure
- Cell Proliferation
- Apoptosis
- Dose-Response Relationship
- Drug
- Quinolines
- Enzyme Inhibitors
- Cell Line
- Tumor
- CDC25 inhibitors
- Cancer therapeutics
- Cell cycle arrest
- Genomic instability
- Patient-derived organoids
- Quinoline-5
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