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Updated: Jan 19, 2026
Drug Repurposing Hypothesis Generation Using the "RE:fine Drugs" System
Published on: December 11, 2016
Drug Repurposing Screen Identifies Novel Classes of Drugs with Anticancer Activity in Mantle Cell Lymphoma
Chengwu Han1, Xueying Yu1, Chunxia Zhang1
1Department of Laboratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China.
Aim And Objective:
Mantle Cell Lymphoma (MCL) is typically an aggressive and rare disease with poor prognosis, therefore new effective therapeutics are urgently needed. Drug repurposing for cancer treatment is becoming increasingly more attractive as an alternative approach to discover clinically approved drugs that demonstrate antineoplastic effect. The objective of this study was to screen an approved drug library and identify candidate compounds with an antineoplastic effect in MCL cells using High-Throughput Screening (HTS) technique.
Materials And Methods:
Using the HTS technique, nearly 3,800 clinically approved drugs and drug candidates were screened in Jeko and Mino MCL cell lines. We also demonstrated the selectivity window of the candidate compounds in six normal cell lines. Further validations were performed in caspase-3/7 apoptosis assay and three-dimensional (3D) multicellular aggregates model using Z138 cell line.
Results:
We identified 98 compounds showing >50% inhibition in either MCL cell line screened, they were distributed across eight unique therapeutic categories and have different mechanisms of action (MOA). We selected alisertib, carfilzomib, pracinostat and YM155 for further validation based on their antiproliferative activity in two MCL cell lines, selectivity to normal cell lines, and drug developing stages in terms of clinical research. Alisertib and carfilzomib showed antiproliferative effect on MCL cell with EC50 = 6 nM and >100-fold selectivity to normal cell lines, especially for alisertib which demonstrated >1000-fold selectivity to 5 out of 6 normal cell lines. Pracinostat and YM155 had potency of 11 and 12 nM in MCL cell with >20-fold selectivity to normal cell lines. All four compounds had been tested in caspase-dependent apoptosis assay. We further validated and demonstrated their anti-MCL effect on cell proliferation and (3D) multicellular aggregates model using Z138 cell line.
Conclusion:
This is the first study to examine such a large library of clinically approved compounds for the identification of novel drug candidates for MCL treatment, the results could be rapidly translated into clinical practice in patients with MCL.
Insights
This study screened nearly 3,800 approved drugs to find new Mantle Cell Lymphoma (MCL) treatments. Four compounds, including alisertib and carfilzomib, showed significant anti-cancer effects and selectivity, offering hope for effective MCL therapies.
Area of Science:
- Oncology
- Pharmacology
- Drug Discovery
Background:
- Mantle Cell Lymphoma (MCL) is an aggressive B-cell cancer with a poor prognosis, necessitating novel therapeutic strategies.
- Drug repurposing of clinically approved agents offers a promising avenue for identifying effective antineoplastic drugs with established safety profiles.
- High-throughput screening (HTS) provides an efficient method for evaluating large compound libraries against cancer cell lines.
Purpose of the Study:
- To screen a library of approximately 3,800 clinically approved drugs and drug candidates for antineoplastic activity against Mantle Cell Lymphoma (MCL) cells.
- To identify candidate compounds with potent anti-MCL effects and favorable selectivity profiles against normal cell lines.
- To validate the efficacy of selected compounds using apoptosis assays and a three-dimensional (3D) multicellular spheroid model.
Main Methods:
- Utilized High-Throughput Screening (HTS) to evaluate 3,800 compounds in Jeko and Mino MCL cell lines.
- Assessed compound selectivity by testing against six normal human cell lines.
- Performed further validation using caspase-3/7 apoptosis assays and a 3D multicellular aggregates model with the Z138 MCL cell line.
Main Results:
- Identified 98 compounds exhibiting >50% inhibition in at least one MCL cell line, spanning eight therapeutic categories.
- Selected alisertib, carfilzomib, pracinostat, and YM155 for further validation based on potency, selectivity, and clinical development stage.
- Alisertib and carfilzomib demonstrated potent antiproliferative effects (EC50 = 6 nM and >100-fold selectivity) in MCL cells, with alisertib showing >1000-fold selectivity against five normal cell lines. Pracinostat and YM155 also showed significant potency (11-12 nM) and selectivity (>20-fold).
Conclusions:
- This study represents the first large-scale screening of approved drugs for MCL treatment potential.
- The identified compounds, particularly alisertib and carfilzomib, demonstrate significant anti-MCL activity and selectivity, warranting further clinical investigation.
- The findings offer a rapid pathway for translating drug repurposing discoveries into clinical practice for MCL patients.
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