ArticleFrontiers in pharmacology2026
Dual MAO A and HSP90 inhibitors enhance anti-PD-1 therapy and suppress colorectal cancer.
Article in Frontiers in pharmacology, 2026. 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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Abstract
Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, yet their efficacy remains limited by tumor resistance, immune-related adverse events, and poor response in microsatellite stable colorectal cancer (CRC). To address these challenges, dual monoamine oxidase A (MAO-A) and heat shock protein 90 (HSP90) inhibitors, MPT1B098 and MPT1B099, were developed and evaluated for their therapeutic potential and immune-modulatory efficacy in CRC. Methods: Human and murine CRC cell lines were treated with MPT1B098 and MPT1B099 to assess their effects in cytotoxicity, cell migration, apoptosis, cell cycle arrest, and cell-surface PD-L1 expression. Western blotting was performed to evaluate key apoptotic and EMT-related markers. In vivo therapeutic efficacy and safety were evaluated using CT26 and MC38 subcutaneous syngeneic tumor models in BALB/c and C57BL/6 mice treated with MPT1B098, MPT1B099, and/or anti-PD1 antibodies. Tumor infiltration of CD8 Results: In vitro, MPT1B098 and MPT1B099 exhibited potent cytotoxicity against human and murine CRC cell lines with sub-micromolar IC Discussion: These findings highlight the dual anti-tumor and immune-modulatory properties of MPT1B098 and MPT1B099, mediated in part through PD-L1 downregulation and enhanced intratumoral T cell infiltration. Dual targeting of MAO-A and HSP90 represents a promising novel strategy to overcome immunotherapy resistance in MSS CRC and enhance the therapeutic efficacy of immune checkpoint blockade.
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