Evidence map›Paper›PMID 41220107›Full record

ArticleCancer biology & therapy2025

Potential therapeutic GSK-3β inhibitor 9-ING-41 is active in combination with venetoclax in double-hit lymphoma (DHL).

Haohao Lei, Yunxia Zhang, Haiqing Zheng, Pengcheng Shi, Xiaolei Wei, Xutao Guo

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Article in Cancer biology & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Haohao LeiDepartment of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.ORCID 0009-0005-1606-8100
Yunxia ZhangDepartment of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.ORCID 0009-0008-2943-4722
Haiqing ZhengDepartment of Nosocomial Infection Management, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.ORCID 0009-0005-8141-3003
Pengcheng ShiDepartment of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
Xiaolei WeiDepartment of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
Xutao GuoDepartment of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.ORCID 0000-0001-6191-2204

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDouble-hit lymphoma (DHL) exhibits aggressive behavior due to dysregulated proliferation and resistance to apoptosis. Current therapies, including R-CHOP, show limited efficacy, necessitating novel strategies. 9-ING-41, a novel ATP-competitive small-molecule inhibitor that targets glycogen synthase kinase-3β (GSK-3β), has emerged as a promising therapeutic agent because of its ability to disrupt oncogenic signaling pathways associated with tumor progression and treatment resistance. However, the antitumor effects of 9-ING-41 in DHL remain unclear. MATERIALS AND

methodsDHL cell lines (Karpas-422 and SuDHL2) were treated with venetoclax and 9-ING-41, either alone or in combination. Cell viability in cytotoxicity assays was assessed using the CCK-8 assay, while apoptosis and cell cycle changes were analyzed via flow cytometry. Western blotting was employed to evaluate alterations in the levels of GSK-3β and WNT/β-catenin pathway proteins following treatment.

resultsIn preclinical studies utilizing DHL cell models, the single agent 9-ING-41 demonstrated robust biological activity through inducing significant G1/S phase cell cycle arrest and triggering apoptosis. When coadministered with venetoclax, a clinically approved BCL-2 inhibitor, the combination exhibited marked synergistic cytotoxicity in DHL cells, achieving superior inhibitory effects compared to either agent alone. The combined treatment enhanced cell cycle arrest, significantly reducing the number of S-phase cells and reinforcing G0/G1 arrest. Further mechanistic studies revealed that the combination modulated key proteins in the GSK-3 pathway and downstream WNT/β-catenin pathway, revealing a potential synergistic mechanism.

conclusionThe demonstrated single-agent efficacy and combination synergy with venetoclax support the potential of 9-ING-41 as a novel therapeutic strategy for DHL. These findings provide a proof-of-concept that may serve as a basis for future preclinical investigations in DHL.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsBridged Bicyclo Compounds, HeterocyclicGlycogen Synthase Kinase 3 betaLymphomaSulfonamidesApoptosisCell Line, TumorCell ProliferationCell SurvivalDrug SynergismHumansBridged Bicyclo Compounds, HeterocyclicGlycogen Synthase Kinase 3 betaSulfonamidesvenetoclax9-ING-41apoptosiscell cycle arrestdouble-hit lymphomaGlycogen synthase kinase-3

Identifiers

PMID41220107
PMCPMC12622347

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.