Maximizing ER-? Degradation Maximizes Activity in a Tamoxifen-Resistant Breast Cancer Model: Identification of GDC-0927.
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ABSTRACT:
SUBMITTER: Kahraman M
PROVIDER: S-EPMC6331158 | biostudies-literature | 2019 Jan
REPOSITORIES: biostudies-literature
Publications
Maximizing ER-α Degradation Maximizes Activity in a Tamoxifen-Resistant Breast Cancer Model: Identification of GDC-0927.
Kahraman Mehmet M Govek Steven P SP Nagasawa Johnny Y JY Lai Andiliy A Bonnefous Celine C Douglas Karensa K Sensintaffar John J Liu Nhin N Lee KyoungJin K Aparicio Anna A Kaufman Josh J Qian Jing J Shao Gang G Prudente Rene R Joseph James D JD Darimont Beatrice B Brigham Daniel D Heyman Richard R Rix Peter J PJ Hager Jeffrey H JH Smith Nicholas D ND
ACS medicinal chemistry letters 20181206 1
The further optimization of ER-α degradation efficacy of a series of ER modulators by refining side-chain substitution led to efficacious selective estrogen receptor degraders (SERDs). A fluoromethyl azetidine group was found to be preferred and resulted in the identification of bis-phenol chromene <b>17ha</b>. In a tamoxifen-resistant breast cancer xenograft model, <b>17ha</b> (ER-α degradation efficacy = 97%) demonstrated tumor regression, together with robust reduction of intratumoral ER-α le ...[more]
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