Hybrid Androgen Receptor Inhibitors Outperform Enzalutamide and EPI‐001 in in vitro Models of Prostate Cancer Drug Resistance
Abstract: Androgen receptor targeted therapies for prostate cancer have serious limitations in advanced stages of the disease. While resistance to the FDA‐approved enzalutamide is extensively documented, novel therapies based on epichlorohydrin scaffolds (EPI) are currently in clinical trials, but display suboptimal pharmacokinetics. Herein, we report the synthesis and biological characterisation of a novel class of compounds designed through covalently linking enzalutamide and EPI‐001 through various triazole based linkers. The compounds display an 18 to 53 fold improvement in the cell killing potency towards C4‐2b prostate cancer (PCa) cells compared to the gold standards of therapy, enzalutamide and EPI‐001. The most promising compounds were proven to exhibit their toxicity exclusively through androgen receptor (AR) mediated pathways. This work sets the basis for the first class of hybrid AR inhibitors which successfully combine two drug moieties – EPI‐001 and enzalutamide – into the same molecule.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Hybrid Androgen Receptor Inhibitors Outperform Enzalutamide and EPI‐001 in in vitro Models of Prostate Cancer Drug Resistance ; day:15 ; month:11 ; year:2022 ; extent:1
ChemMedChem ; (15.11.2022) (gesamt 1)
- Creator
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Nicolescu, Radu Costin Bizga
Maylin, Zoe R.
Pérez‐Areales, Francisco Javier
Iegre, Jessica
Pandha, Hardev S.
Asim, Mohammad
Spring, David R.
- DOI
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10.1002/cmdc.202200548
- URN
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urn:nbn:de:101:1-2022111614021867952131
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:21 AM CEST
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Associated
- Nicolescu, Radu Costin Bizga
- Maylin, Zoe R.
- Pérez‐Areales, Francisco Javier
- Iegre, Jessica
- Pandha, Hardev S.
- Asim, Mohammad
- Spring, David R.
Other Objects (12)
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Molecular Mechanisms of Enzalutamide Resistance in Prostate Cancer
Approaching personalized medicine: preclinical evaluation of enzalutamide-resistant castration-resistant prostate cancer and mutated forms of the androgen receptor targeted by a new androgen receptor inhibitor
Androgen receptor degradation by the proteolysis-targeting chimera ARCC-4 outperforms enzalutamide in cellular models of prostate cancer drug resistance
Enzalutamide Reduces Oxycodone Exposure in Men with Prostate Cancer
Role of the androgen receptor in breast cancer and preclinical analysis of enzalutamide
Immune evasion strategies of neuroendocrine-like Enzalutamide resistant prostate cancer
Enzalutamide induces cytotoxicity in desmoplastic small round cell tumor independent of the androgen receptor
Hedgehog/Gli supports androgen signaling in androgen deprived and androgen independent prostate cancer cells
Interleukin-23 Represses the Level of Cell Senescence Induced by the Androgen Receptor Antagonists Enzalutamide and Darolutamide in Castration-Resistant Prostate Cancer Cells
Enzalutamide Sensitizes Castration‐Resistant Prostate Cancer to Copper‐Mediated Cell Death
KEYNOTE-991: pembrolizumab plus enzalutamide and androgen deprivation for metastatic hormone-sensitive prostate cancer
Preclinical studies using cisplatin/carboplatin to restore the Enzalutamide sensitivity via degrading the androgen receptor splicing variant 7 (ARv7) to further suppress Enzalutamide resistant prostate cancer
Molecular Mechanisms of Enzalutamide Resistance in Prostate Cancer
Approaching personalized medicine: preclinical evaluation of enzalutamide-resistant castration-resistant prostate cancer and mutated forms of the androgen receptor targeted by a new androgen receptor inhibitor
Androgen receptor degradation by the proteolysis-targeting chimera ARCC-4 outperforms enzalutamide in cellular models of prostate cancer drug resistance
Enzalutamide Reduces Oxycodone Exposure in Men with Prostate Cancer
Role of the androgen receptor in breast cancer and preclinical analysis of enzalutamide
Immune evasion strategies of neuroendocrine-like Enzalutamide resistant prostate cancer
Enzalutamide induces cytotoxicity in desmoplastic small round cell tumor independent of the androgen receptor
Hedgehog/Gli supports androgen signaling in androgen deprived and androgen independent prostate cancer cells
Interleukin-23 Represses the Level of Cell Senescence Induced by the Androgen Receptor Antagonists Enzalutamide and Darolutamide in Castration-Resistant Prostate Cancer Cells
Enzalutamide Sensitizes Castration‐Resistant Prostate Cancer to Copper‐Mediated Cell Death
KEYNOTE-991: pembrolizumab plus enzalutamide and androgen deprivation for metastatic hormone-sensitive prostate cancer
Preclinical studies using cisplatin/carboplatin to restore the Enzalutamide sensitivity via degrading the androgen receptor splicing variant 7 (ARv7) to further suppress Enzalutamide resistant prostate cancer
Molecular Mechanisms of Enzalutamide Resistance in Prostate Cancer
Approaching personalized medicine: preclinical evaluation of enzalutamide-resistant castration-resistant prostate cancer and mutated forms of the androgen receptor targeted by a new androgen receptor inhibitor
Androgen receptor degradation by the proteolysis-targeting chimera ARCC-4 outperforms enzalutamide in cellular models of prostate cancer drug resistance
Enzalutamide Reduces Oxycodone Exposure in Men with Prostate Cancer
Role of the androgen receptor in breast cancer and preclinical analysis of enzalutamide
Immune evasion strategies of neuroendocrine-like Enzalutamide resistant prostate cancer
Enzalutamide induces cytotoxicity in desmoplastic small round cell tumor independent of the androgen receptor
Hedgehog/Gli supports androgen signaling in androgen deprived and androgen independent prostate cancer cells
Interleukin-23 Represses the Level of Cell Senescence Induced by the Androgen Receptor Antagonists Enzalutamide and Darolutamide in Castration-Resistant Prostate Cancer Cells