New Potent Inhibitor of Transforming Growth Factor-Beta (TGFβ) Signaling that is Efficacious against Microsatellite Stable Colorectal Cancer Metastasis in Combination with Immune Checkpoint Therapy in Mice

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dc.contributor.authorTauriello, Daniele V. F.
dc.contributor.authorSancho, Elena
dc.contributor.authorByrom, Daniel
dc.contributor.authorSánchez Zarzalejo, Carolina
dc.contributor.authorSalvany, Maria
dc.contributor.authorHenriques, Ana
dc.contributor.authorPalomo Ponce, Sergio
dc.contributor.authorSevillano, Marta
dc.contributor.authorHernando Momblona, Xavier
dc.contributor.authorMatarin, Joan A.
dc.contributor.authorRamos, Israel
dc.contributor.authorRuano, Irene
dc.contributor.authorPrats, Neus
dc.contributor.authorBatlle, Eduard
dc.contributor.authorRiera i Escalé, Antoni
dc.date.accessioned2024-11-26T18:32:51Z
dc.date.available2024-11-26T18:32:51Z
dc.date.issued2024-12-01
dc.date.updated2024-11-26T18:32:51Z
dc.description.abstractBlockade of the TGFβ signaling pathway has emerged from preclinical studies as a potential treatment to enhance the efficacy of immune checkpoint inhibition in advanced colorectal cancer (CRC) and several other types of cancer. However, clinical translation of first-generation inhibitors has shown little success. Here, we report the synthesis and characterization of HYL001, a potent inhibitor of TGFβ receptor 1 (ALK5), that is approximately 9 times more efficacious than the structurally related compound galunisertib, while maintaining a favorable safety profile. HYL001 in combination with immune checkpoint blockade (anti-PD1) eradicates liver metastases generated in mice by microsatellite stable, aggressive colorectal cancer tumors at doses where galunisertib is ineffective.
dc.format.extent16 p.
dc.format.mimetypeapplication/pdf
dc.identifier.idgrec752004
dc.identifier.idimarina6694534
dc.identifier.issn2575-9108
dc.identifier.urihttps://hdl.handle.net/2445/216759
dc.language.isoeng
dc.relation.isformatofReproducció del document publicat a: https://doi.org/10.1021/acsptsci.4c00374
dc.relation.ispartof2024
dc.relation.urihttps://doi.org/10.1021/acsptsci.4c00374
dc.rightscc-by (c) Tauriello, Daniele V. F., et al., 2024
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/es/*
dc.sourceArticles publicats en revistes (Química Inorgànica i Orgànica)
dc.subject.classificationCàncer
dc.subject.classificationAnatomia
dc.subject.classificationMetàstasi
dc.subject.otherCancer
dc.subject.otherAnatomy
dc.subject.otherMetastasis
dc.titleNew Potent Inhibitor of Transforming Growth Factor-Beta (TGFβ) Signaling that is Efficacious against Microsatellite Stable Colorectal Cancer Metastasis in Combination with Immune Checkpoint Therapy in Mice
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:eu-repo/semantics/publishedVersion

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