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Development of dual casein kinase 1?/1? (CK1?/?) inhibitors for treatment of breast cancer.

ABSTRACT: Casein kinase 1?/? have been identified as promising therapeutic target for oncology application, including breast and brain cancer. Here, we described our continued efforts in optimization of a lead series of purine scaffold inhibitors that led to identification of two new CK1?/? inhibitors 17 and 28 displaying low nanomolar values in antiproliferative assays against the human MDA-MB-231 triple negative breast cancer cell line and have physical, in vitro and in vivo pharmacokinetic properties suitable for use in proof of principle animal xenograft studies against human cancers.

SUBMITTER: Monastyrskyi A

PROVIDER: S-EPMC5803353 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Development of dual casein kinase 1δ/1ε (CK1δ/ε) inhibitors for treatment of breast cancer.

Monastyrskyi Andrii A Nilchan Napon N Quereda Victor V Noguchi Yoshihiko Y Ruiz Claudia C Grant Wayne W Cameron Michael M Duckett Derek D Roush William W

Bioorganic & medicinal chemistry 20171215 3

Casein kinase 1δ/ε have been identified as promising therapeutic target for oncology application, including breast and brain cancer. Here, we described our continued efforts in optimization of a lead series of purine scaffold inhibitors that led to identification of two new CK1δ/ε inhibitors 17 and 28 displaying low nanomolar values in antiproliferative assays against the human MDA-MB-231 triple negative breast cancer cell line and have physical, in vitro and in vivo pharmacokinetic properties s ...[more]

PMID: 29289448

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Development of highly selective casein kinase 1?/1? (CK1?/?) inhibitors with potent antiproliferative properties.

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Targeting Casein Kinase 1 (CK1) in Hematological Cancers.

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Alleviation of behavioral hypersensitivity in mouse models of inflammatory pain with two structurally different casein kinase 1 (CK1) inhibitors.

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Casein kinase 1 (CK1) promotes the proliferation and metastasis of glioma cells via the phosphatidylinositol 3 kinase-matrix metalloproteinase 2 (AKT-MMP2) pathway.

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| S-EPMC8713180 | biostudies-literature

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